COLOMATE: Colorectal Cancer Liquid Biopsy Screening Protocol for Molecularly Assigned Therapy
Conditions: Metastatic Colon Adenocarcinoma, Metastatic Rectal Adenocarcinoma, Stage III Colon Cancer AJCC v8, Stage III Rectal Cancer AJCC v8, Stage IIIA Colon Cancer AJCC v8, Stage IIIA Rectal Cancer AJCC v8, Stage IIIB Colon Cancer AJCC v8, Stage IIIB Rectal Cancer AJCC v8, Stage IIIC Colon Cancer AJCC v8, Stage IIIC Rectal Cancer AJCC v8, Stage IV Colon Cancer AJCC v8, Stage IV Rectal Cancer AJCC v8, Stage IVA Colon Cancer AJCC v8, Stage IVA Rectal Cancer AJCC v8, Stage IVB Colon Cancer AJCC v8, Stage IVB Rectal Cancer AJCC v8, Stage IVC Colon Cancer AJCC v8, Stage IVC Rectal Cancer AJCC v8, Unresectable Colon Adenocarcinoma, Unresectable Rectal Adenocarcinoma
Sponsor: Academic and Community Cancer Research United

 
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ACCRU-GI-1611 
Academic and Community Cancer Research United (ACCRU)  
 
ACCRU-GI-1611 COLOMATE: COlorectal Cancer Liquid BiOpsy Screening Protocol for 
Molecularly Assigned ThErapy 
 
Amendment 2– January 28, 2021 
 
 
Summary of Changes 
 
Protocol section updated 
Nature of change 
Title Page 
• Stat personnel change – Joseph Larson  
• Updated Document History 
Section 3.0, Patient Eligibility 
• Section 3.19 updated to clarify that one of two 
conditions must be met 
Section 4.0, Test Schedule 
• 28 days prior to registration changed to 60 days prior 
to registration 
• Tumor assessment test removed  
• Footnote 1 Removed 
• Footnotes renumbered  
Section 6.0, Registration/Randomization 
Procedures 
• Added Exemption: Guardant360 tests completed ≤60 
days prior to registration will be accepted  
Section 14.0, Body Fluid Biospecimens 
• Instructional text updated throughout for ordering 
Guardant 360 kits 
Section 16.0, Statistical Considerations and 
Methodology 
• Edit of primary endpoint for actionable genomic 
profile and trial recommendations  
• Edit of secondary endpoint for companion trial 
enrollment   
• Addition of confidence interval table in sample size 
section  
• Analysis plan edit for primary endpoint, goal of 20% 
of patients with actionable genomic profiles.  
• Addition of secondary endpoint analysis, subsequent 
screening, goal of 75% patients with actionable 
genomic profiles.   
Appendix I: ACCRU Informed Consent 
• Removed the need for CT or MRI of tumor 
• Added information regarding the protocol selection 
process based off of the Guardant360 blood test 
Editorial and administrative changes have been made throughout the protocol but do not affect the 
scientific content or meaning. 
A replacement protocol is provided.  Please replace the current copy with the one attached. 
Please keep this summary of changes with your protocol 
 
 

 
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ACCRU-GI-1611 
Amendment 2 
 
Academic and Community Cancer Research United (ACCRU) 
 
COLOMATE: COlorectal Cancer Liquid BiOpsy Screening Protocol for Molecularly Assigned 
ThErapy 
 
 
For any communications regarding this protocol, please contact the 
person indicated on the Protocol Resource Page. This is a stand-alone 
document found on the ACCRU website 
 
 
Study Chairs 
 
ACCRU: 
 
  
 
Study Co-chairs: 
 
 
Statistician: 
  
 
 
 
 
√ Study contributor(s) not responsible for patient care. 
 
 
Research Coordinating Center 
Academic and Community Cancer Research United 
 
 
 
Document History 
(effective date) 
Version 1 
May 15, 2017 
Preactivation 
Amendment 
 
November 8, 2018 
 
 
Activation 
November 1, 2019 
Amendment 1 
March 4, 2020 
Amendment 2 
January 28, 2021 
 
 
 

 
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ACCRU-GI-1611 
Amendment 2 
 
 
 
 
 
Index 
 
 
 
 
1.0 
Schema 
Background 
2.0 Goals 
3.0 Patient Eligibility 
4.0 Test Schedule 
5.0  Grouping Factors 
6.0 Registration Procedures 
7.0 Protocol Treatment 
8.0 Dosage Modification Based on Adverse Events  
9.0 Ancillary Treatment/Supportive Care 
10.0  Adverse Event (AE) Reporting and Monitoring 
11.0 Treatment Evaluation Using RECIST Guideline 
12.0 Descriptive Factors 
13.0  Treatment/Follow-up Decision at Evaluation of Patient 
14.0 Body Fluid Biospecimens 
15.0 Drug Information 
16.0 Statistical Considerations and Methodology 
17.0 Pathology Considerations/Tissue Biospecimens 
18.0 Records and Data Collection Procedures 
19.0 Budget 
20.0 References 
Appendix I ACCRU Informed Consent Template 
  
 
 
 
 
 
 

 
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Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
YES 
NO 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Registration 
Guardant360 Test Completion 
≤ 60 days Prior to Registration 
Fax Authorization Form to 
Guardant Health to Allow 
ACCRU to Collect CfDNA 
Results 
Blood Submission to Guardant 
for CfDNA Testing 
Off Study 
CfDNA Testing and Receipt 
of Results 
Receive COLOMATE 
Recommendation Letter 
Patients have the option to register on COLOMATE for a 
maximum of 3 times or at the discretion of the Study Chair. 
Reference section 6.2 for instructions. 

 
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1.0 
Background 
 
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States (Jemal, 
Siegel et al. 2010). Over the past two decades, overall survival for patients with metastatic disease 
has steadily improved. To build on this progress, comprehensive efforts are needed to identify 
and treat actionable molecular alterations. Already, this approach has been used to enhance the 
benefit of anti-EGFR (Oliner, Douillard et al. 2013) and anti-PD-1 (Le, Uram et al. 2015) 
monoclonal antibodies. This screening protocol is designed to identify actionable genomic 
alterations, and then facilitate accrual to molecularly assigned therapies. 
 
Several basket trials are ongoing to match tumor genotype with targeted therapies. Nonetheless, 
the impact of these trials thus far has been limited by operational and technical challenges. For 
example, at MD Anderson Cancer Center large-scale genomic testing was performed on 2,000 
consecutive patients. Of these, 39% of patients had a potentially actionable tumor mutation, but 
only 11% were enrolled on a genotype-matched clinical trial (Meric-Bernstam, Brusco et al. 
2015). This experience identified several barriers to trial enrollment, including use of non-
investigational treatments off trial, excessive delays in receiving test results, declining 
performance status, and lack of available tumor tissue for testing. To capture the value of 
mutational testing, it is critical to have an efficient screening process, provide convenient access 
to clinical trials, and offer treatments with a high probability of clinical benefit. 
 
1.1 
Study Rationale 
 
Precision medicine is predicated on the notion that therapeutic strategies can be tailored 
to a tumor’s unique molecular profile. Nonetheless, in practice most targeted therapeutic 
strategies provide limited clinical benefit. There are several reasons that many targeted 
therapies fail to provide durable disease control. First, tumor heterogeneity allows rapid 
outgrowth of resistant subclones (Gerlinger, Rowan et al. 2012). Second, molecular 
targets that are actionable in one tumor type may not be actionable in another tumor type 
(Kopetz, Desai et al. 2015). Finally, targeted therapies may induce feedback re-activation 
of upstream receptors and alternate signaling pathways (Corcoran, Ebi et al. 2012, Mao, 
Tian et al. 2013). To understand the drivers of sensitivity and resistance, it is critical to 
understand a tumor’s molecular profile before therapy, during therapy, and at 
progression. 
 
Access to tumor tissue hinders the ability to understand and treat the molecular drivers of 
resistance. In recent years, technology has emerged to identify genomic alterations from a 
routine blood draw. In a series of simultaneously obtained blood and tissue biopsies, 
concordance between circulating cell free tumor DNA (cfDNA) and tissue mutation 
profiles approached 90% (Kim, Lee et al. 2015, Janku, Huang et al. 2016, Sacher, 

 
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Paweletz et al. 2016). For patients with treatment refractory disease, sampling cfDNA for 
genomic alterations may be particularly valuable. A peripheral blood draw spares a 
patient an invasive tissue biopsy, and offers rapid, safe, and cost-effective genomic 
profiling. In addition, blood-based biopsies offer anatomically unbiased genomic 
profiling, allowing detection of both dominant clones and resistant sub-clones.  
 
The use of cfDNA in treatment-refractory metastatic CRC is feasible, with tumor DNA 
detected in most patients (Bettegowda, Sausen et al. 2014). Among patients who have 
progressed on anti-EGFR therapy, cfDNA is already being used to identify molecular 
drivers of resistance. Some of these drivers, such as ERBB2 amplification, are often 
present in original diagnostic tumor tissue, and likely represent a primary driver of EGFR 
resistance (Strickler, Zhang et al. 2015). Other genomic alterations, including KRAS, 
NRAS, BRAF and EGFR somatic mutations may emerge under the selective pressure of 
anti-EGFR therapy (Diaz, Williams et al. 2012, Morelli, Overman et al. 2013, Morelli, 
Overman et al. 2014, Arena, Bellosillo et al. 2015). Additionally, cfDNA profiling often 
reveals concurrent gene mutations and copy number alterations. In a case series of 56 
patients with RAS WT/ MET non-amplified tumors treated with anti-EGFR therapy, 14% 
of patients developed MET amplification upon progression (Morelli, Overman et al. 
2013). Of these patients with acquired MET amplification, half also had concurrent RAS 
mutations (Morelli, Overman et al. 2014). These results have been reproduced in an 
ongoing clinical trial of cabozantinib plus panitumumab (NCT02008383). Among the 
first 26 patients with EGFR-refractory metastatic CRC receiving cfDNA profiling, 5 
patients (19%) had MET amplified tumors (Strickler, Zhang et al. 2015). Concurrent 
BRAF and KRAS somatic mutations were detected in 2 out of 5 (40%) of these patients. 
These results illustrate the genomic complexity of acquired resistance. 
 
Approximately 30-40% of patients with EGFR-refractory metastatic CRC have an 
“actionable” molecular alteration. These actionable alterations include, but are not limited 
to MET amplification (10-15%), EGFR somatic mutations (10%), and ERBB2 
amplification or somatic mutations (7%). Additionally, patients with metastatic CRC may 
have other actionable alterations, including FGFR amplifications or translocations (5%), 
RET fusions (1%), and TRK fusion (<1%). This protocol will utilize blood-based 
genomic profiling to identify and treat actionable genomic alterations. 
 
 
2.0 
Goals  
 
2.1 
Primary 
 
2.11 
To perform blood-based genomic profiling on patients with treatment refractory 
metastatic CRC to facilitate accrual to molecularly assigned therapies.  
 
2.12 
To facilitate clinically annotated genomic analyses. 
 
 
3.0 
Patient Eligibility  
 
3.1 
Inclusion Criteria  
 
3.11 
Age ≥ 18 years. 
 

 
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3.12 
Histological confirmation of adenocarcinoma of the colon or rectum that is 
metastatic and/ or unresectable. 
 
3.13 
Progression, intolerance, or contraindication to a fluoropyrimidine (e.g., 5-
fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal 
antibody (bevacizumab, ziv-aflibercept, or ramucirumab), and an anti-PD-1 
monoclonal antibody (nivolumab or pembrolizumab) if tumor has deficient 
mismatch repair proteins (dMMR) or is microsatellite instability-high (MSI-H).   
 
3.14 
For patients with KRAS and NRAS wild-type tumors, progression, intolerance, or 
contraindication to an anti-EGFR monoclonal antibody (cetuximab or 
panitumumab). Note: If tissue is known to be positive for HER2 expression (IHC 
3+) or the tumor has ERBB2 (HER2) amplification detected by a CLIA-certified 
assay, prior treatment with anti-EGFR therapy is not required. 
 
3.15 
At least one site of disease that is measurable by RECIST criteria (version 1.1) 
that has not been previously irradiated; if the patient has had previous radiation to 
the target lesion(s), there must be evidence of progression since the radiation (see 
section 11).  
 
3.16 
Life expectancy ≥3 months per estimation of investigator. 
 
3.17 
ECOG Performance Status (PS) 0, 1, or 2 (Form is available on the ACCRU web 
site 
  
 
3.18 
Capable of understanding and complying with the protocol requirements and has 
signed the informed consent document. 
 
3.19 
Satisfy at least one of the following two conditions:  
 
• 
Willing and able to provide blood sample for screening purposes (See 
Section 14.0). 
 
• 
Guardant360 testing completed ≤ 60 days prior to registration is available for 
COLOMATE steering committee to review.  
 
3.2 
Exclusion Criteria 
 
3.21 
Evidence within the last 3 years of another malignancy which required systemic 
treatment. EXCEPTIONS: Non-melanotic skin cancer,  carcinoma-in-situ of the 
cervix, or localized prostate cancer with a current PSA of < 1.0mg/dL on 2 
successive evaluations, at least 90 days apart, with the most recent evaluation no 
more than 4 weeks prior to registration.   
 
3.22 
Unable or unwilling to abide by the study protocol or cooperate fully with the 
investigator or designee. 
 
3.23 
History of solid organ transplantation.  
 
3.24 
Pregnant or planning to become pregnant within the next 12 months.   
 

 
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4.0 
Test Schedule 
 
Tests and Procedures 
Active Monitoring 
≤60 days prior 
to registration 
Registration/ 
Baseline 
30 Days after  
Registration (±3 days) 
Informed Consent 
X 
 
 
Demographics 
X 
 
 
Medical and Cancer 
History 
X 
 
 
Physical Examination 
X 
 
 
Height 
X 
 
 
Weight 
X 
 
 
Vital Signs 
X 
 
 
ECOG Performance 
Status 
X 
 
 
Cell-Free DNA 
Analysis1,R 
 
X2 
 
COLOMATE 
Companion Trial 
Recommendation 
Form 
 
 
X3 
 
 
Nurse/CRA phone 
contact 
 
 
X4 
1 
Kits are required for this collection. Please reference Section 14 for instructions. Sites will 
access results through the Guardant Health portal: 
Sites 
will be notified by Guardant Health via email when results are available in the portal. 
Following receipt of results, sites must email the de-identified results to 
 See detailed instructions on the ACCRU website under 
Manuals and Forms. 
2 
If the patient has received Guardant360 testing ≤ 60 days of registration, these test results will 
be accepted for study and cell-free DNA analysis will not be repeated (no blood drawn at 
baseline). To receive test results, if not already available, the patient will fill out the 
Authorization to Use and Disclose Health Information form found on the ACCRU website 
under Manuals and Forms. Guardant will send the results to the site contacts they list on the 
authorization form. Sites will then email the de-identified results to 
See detailed instructions on the ACCRU website under 
Manuals and Forms. 
3 
Complete top portion of COLOMATE Companion Trial Recommendation Form and email to 
The COLOMATE steering committee will complete the 
form and send to treating physician and CRA within 5 business days of receipt of 
Guardant360 results. The treating physician/CRA will provide this form to the appropriate 
companion trial study team. 
4 
Nurse/CRA to call patient 30 days after the date of registration to collect status of registration 
to companion trial needed to complete On-Study Form.   
 
R Research funded (see Section 19) 
5.0 
Grouping Factors  
 
NONE 

 
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6.0 
Registration Procedures 
 
6.1 
Initial Registration 
 
6.11 
To register a patient, access the ACCRU web page at 
 go to the Remote Application 
section, click on “Registration” and enter the registration/ randomization 
application. The registration application is available 24 hours a day, 7 days a 
week. Back up and/or system support contact information is available on the 
Web site. If unable to access the Web site, call the Academic and Community 
Cancer Research United (ACCRU) Registration Office at 
 
between the hours of 8 a.m. and 4:30 p.m. Central Time (Monday through 
Friday). 
 
Instructions for the registration application are available on the above web page 
under the Remote Application section, “Remote Application Training.”  
 
Prior to initiation of protocol study intervention, this process must be completed 
in its entirety and an ACCRU subject ID number must be available as noted in 
the instructions. It is the responsibility of the individual and institution registering 
the patient to confirm the process has been successfully completed prior to 
release of the study agent. Patient registration via the registration/randomization 
application can be confirmed in any of the following ways: 
 
• 
Contact the ACCRU Registration Office 
 If the patient was 
fully registered, the Registration Office staff can access the information from 
the centralized database and confirm the registration. 
 
• 
Refer to “Remote Registration, Installation & Entry Instructions” under 
“Training Material Manuals.” 
 
6.2 
Subsequent Registrations 
 
6.21 
To register a patient, fax (
) a completed eligibility checklist to the 
Academic and Community Cancer Research United (ACCRU) Registration 
Office between 8 a.m. and 4:30 p.m. central time Monday through Friday.  
 
 
NOTE: Patients have the option to register on COLOMATE for a maximum of 3 times or 
at the discretion of the Study Chair. Patients must reconsent and meet eligibility 
criteria in section 3 and will receive a new patient ID.   
 
6.3 
At the time of registration, the following will be recorded:  
 
• 
Patient has given permission to share his/her data for future research to learn about, 
prevent, or treat cancer or other health problems (for example: diabetes, Alzheimer’s 
disease, or heart disease).  
• 
Patient has given permission for ACCRU to share his/her data to outside researchers. 
 
6.4 
Documentation of IRB approval must be on file with ACCRU before an 

 
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investigator may register any patients. Approvals should be uploaded through the 
online ACCRU Regulatory Management System (ARMS). 
 
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file with ACCRU no less than annually. Approvals 
should be uploaded through the online ACCRU Regulatory Management System 
(ARMS). If the necessary documentation is not submitted in advance of attempting 
patient registration, the registration will not be accepted and the patient may not be 
enrolled in the protocol until the situation is resolved. 
 
Submission of annual IRB approvals to ACCRU is required until the study is closed 
through your IRB*. 
 
*Please note, if the study site IRB determines that the study meets requirements for a 
minimal risk study, per the Revised Common Rule, any study approved after January 21, 
2019, is not required to provide continuing/annual reviews. 
 
6.5 
Prior to accepting the registration, the registration application will verify the following: 
 
• 
IRB approval at the registering institution 
• 
Patient eligibility 
• 
Existence of a signed consent form 
• 
Existence of a signed authorization for use and disclosure of protected health 
information  
 
 
 
6.6 
Study-specific activities cannot begin prior to registration and must begin ≤30 days after 
registration. 
 
 
NOTE: Guardant360 testing completed ≤ 60 days prior to registration will be accepted. 
 
6.7 
Pretreatment tests/procedures (see Section 4) must be completed within the guidelines 
specified on the test schedule. 
 
6.8 
Study-specific activities on this protocol must commence at an ACCRU institution under 
the supervision of a medical oncologist.  
 
6.9 
Blood draw kits are available on site. 
 
 
EXEMPTION: Guardant360 tests completed ≤ 60 days prior to registration will be 
accepted. 
 
 
7.0 
Protocol Treatment 
 
This is a screening protocol to identify genomic alterations via cfDNA and facilitate enrollment 
onto COLOMATE companion clinical trials. Standard genomic profiling will be performed using 
the Guardant360 assay in Guardant Health's CLIA-certified laboratory. Guardant360 is a 
commercially available cfDNA genotyping assay; the genomic results from Guardant360 may be 
used in conjunction with other data to guide patient care. Guardant360 is not being used as an 
investigational device in this study, nor is the purpose to validate its use in patient selection for 
study treatments. 

 
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7.1 
Guardant 360 test  
 
 
7.11 
Patients who had Guardant360 test completed ≤60 days prior to registration. 
 
If the patient has received Guardant 360 testing ≤60 days prior to registration, 
these test results will be accepted for study and cell-free DNA analysis will not 
be repeated.  
 
To receive test results, if not already available, the patient will fill out the 
Authorization to Use and Disclose Health Information form found on the 
ACCRU website under Manuals and Forms that the treating physician/CRA will 
fax to Guardant Health.   
 
7.12 
Patients who do not have Guardant360 results or Guardant360 results completed 
>60 days prior to registration.  
 
 
 
Follow section 14 to submit blood samples to Guardant Health. 
 
7.2 
Site access to Guardant360 testing results 
 
 
7.21 
Patients who had Guardant360 results completed ≤60 days prior to registration. 
 
Guardant will send the results to the site contacts they list on the authorization 
form. Sites will then email the de-identified results (including ACCRU patient 
ID) to 
  
 
7.22 
Patients who do not have Guardant360 results or Guardant360 results completed 
>60 days prior to registration.  
 
Sites will access Guardant360 results through the Guardant Health portal: 
 
Following receipt of results, sites 
must email the de-identified results (including ACCRU patient ID) to 
See detailed instructions on the ACCRU 
website under Manuals and Forms.  
 
7.3 
COLOMATE Committee Recommendation 
 
7.31 
At the time of Guardant360 kit submission or at the time of faxing authorization 
form to Guardant Health, sites will complete the top portion of the COLOMATE 
Companion Trial Recommendation Form and email to 
The COLOMATE steering committee will 
complete the form and send the treating physician/CRA the COLOMATE 
Companion Trial Recommendation form with companion trial recommendations 
within 5 business days of receipt of Guardant360 test results. If a patient qualifies 
to be screened for a companion clinical trial, the treating physician/CRA will 
provide this form to the appropriate companion trial study team.  
 
COLOMATE recommendations are not binding and the local investigator and/or 

 
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treating physician may determine the preferred companion trial taking into 
consideration best clinical evidence and the patient’s clinical circumstances.  
 
If additional assistance with companion trial recommendations are needed, local 
investigators and/or treating physicians may contact the COLOMATE steering 
committee at 
 
 
7.32 
Actionable alteration is defined as a genomic alteration/mutation profile that 
qualifies a patient to be screened for one companion trial. 
 
7.4 
Patients for whom 1 actionable alteration is identified 
 
If an actionable alteration is identified, the treating physician will be notified of any 
available COLOMATE companion trials on the COLOMATE Companion Trial 
Recommendation Form.  
 
7.41 
Patients who choose to enroll in a COLOMATE companion trial and meet 
eligibility criteria will be treated according to that companion trial protocol. 
 
7.42 
Patients who decline participation on the COLOMATE companion trial or do not 
meet eligibility criteria can subsequently register with COLOMATE ≥60 days 
after previous registration for a maximum of 3 times or at the discretion of the 
Study Chair.  
 
7.5 
Patients for whom ≥2 actionable alterations are identified 
 
If more than one actionable alteration is identified, COLOMATE companion trial 
recommendations will be prioritized according to the following algorithm: 1) fusions; 2) 
amplifications; 3) all other alterations.  If the algorithm does not assign a patient to one 
companion clinical trial, the report will be referred to the COLOMATE PI and/or a 
COLOMATE steering committee designee and statistician for adjudication.   
 
7.51 
Patients who choose to enroll in a COLOMATE companion trial and meet 
eligibility criteria will be treated according to that companion trial protocol. 
 
7.52 
Patients who decline participation on a COLOMATE companion trial or do not 
meet eligibility criteria can re-register with COLOMATE ≥60 days after previous 
registration for maximum of 3 times or at the discretion of the Study Chair.  
 
7.6 
Patients for whom no actionable alteration is identified 
 
If no actionable alteration is identified, the treating physician will be notified of any other 
COLOMATE companion trials for which the patient may be eligible on the COLOMATE 
Companion Trial Recommendation Form. The patient can re-register with COLOMATE 
≥60 days after previous registration for maximum of 3 times or at the discretion of the 
Study Chair. 
 
 
7.7 
Evaluation procedures 
 
7.71 
Each patient will be contacted by telephone 30 days (± 3 days) after registration 
to document the patient’s status of registration to a companion study. This 

 
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information is needed to complete the On-Study form.  
 
 
8.0 
Dosage Modification Based on Adverse Events  
 
 
None for this screening protocol. 
 
9.0 
Ancillary Treatment/Supportive Care 
 
 
None for this screening protocol. 
 
10.0 
Adverse Event (AE) Reporting and Monitoring 
 
Adverse Events will not be collected for this screening protocol. 
 
11.0 
Treatment Evaluation Using RECIST Guideline 
 
NONE 
 
12.0 
Descriptive Factors  
 
12.1 
Microsatellite instability (MSI)/Mismatch repair (MMR) status (MSI-H/deficient MMR 
vs. MSS/ proficient MMR) 
 
12.2 
KRAS (mutated vs. wildtype) 
 
12.3 
NRAS (mutated vs. wildtype) 
 
12.4 
BRAF V600E (mutated vs. wildtype vs. unknown) 
 
12.5 
Primary tumor site: Cecum, ascending colon, hepatic flexure, transverse colon, splenic 
flexure, descending colon, sigmoid colon, rectosigmoid junction, rectum vs. unknown vs. 
multiple  
 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient  
 
 
This is a screening protocol and patients will not receive any treatment.   
 
13.1 
A patient is deemed ineligible if after registration, it is determined that at the time of 
registration, the patient did not satisfy each and every eligibility criteria for study entry. 
The patient will go directly to off study.  
 
• 
If the patient had cfDNA testing, all data up until the point of confirmation of 
ineligibility must be submitted  
 
13.2 
A patient is deemed a cancel if he/she is removed from the study for any reason other 
than ineligibility before any study-specific activities take place. On-study material must 
be submitted. No further data submission is necessary. 
 
• 
If the patient never had cfDNA testing, only on-study material must be submitted 
 

 
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14.0 
Body Fluid Biospecimens  
 
14.1 
Summary Table of Research Blood/Blood Products for This Protocol  
 
Indicate if 
specimen 
is 
mandatory 
or optional 
Collection 
tube 
description 
and/or 
additive 
(color of 
tube top) 
Volume to 
collect per 
tube 
(number 
of tubes to 
be 
collected) 
Blood 
product 
being 
processed 
and 
submitted by 
participating 
site 
Baseline 
Storage 
/shipping 
conditions4 
Mandatory 
Streck tube 
10 mL (2) 
Whole blood 
X 
Room 
temperature 
 
 
 
NOTE: If the patient has received Guardant360 testing ≤60 days of registration, these test results 
will be accepted for study and cell-free DNA analysis will not be repeated; no blood 
drawn at baseline. To receive test results, see section 7.0.  
 
14.2 
Kits are required for this study. 
 
14.21 In order to receive an initial kit shipment and access to the Guardant portal, fill 
out the Guardant Site Setup form for each treating location and email it to  
ACCRU at 
 
 
14.22 ACCRU will notify Guardant Health once each site is activated and will help 
facilitate portal access requests and the initial kit shipment. Guardant Health will 
provide portal access 
and will ship the initial 
supply of  kits to each site. Following the initial shipment, each site can request 
that kits be refreshed/replaced by completing the “Kit Reorder Form” and 
emailing it to Guardant Health Client Services Team at 
 
 
14.3 
Shipping and Handling 
 
14.31 Guardant360 (Streck Tube) 
 
 
14.311 Complete the Test Requisition Form and barcode labels. 
 
14.312 Ship tubes the same day as collection with properly prepared gel packs. 
Do not freeze gel packs. Use as is. 
 
14.313 Place the kit into the preprinted FedEx Clinical Pak and call FedEx for a 
pickup to be shipped to Guardant Health. 
 
14.314 Detailed Blood Draw and Shipping Instructions are located on the 
ACCRU website under Manuals and Forms. 
 
14.4 
Return of Genetic Testing Research Results 
 
Results of CLIA-certified assays (e.g., Guardant360) are permitted to be shared with 

 
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ACCRU-GI-1611 
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patients and their treating physicians. The return of genetic testing research results do not 
apply to patients who completed Guardant360 testing outside of the COLOMATE trial.  
 
15.0 
Drug Information 
 
Patients will be treated according to companion treatment protocol or clinical standard of care.  
 
16.0 
Statistical Considerations and Methodology  
 
16.1 
Overview 
 
This is a screening protocol that is designed to identify patients with actionable genomic 
alterations and recommend them to an appropriate companion trial. A patient who has an 
actionable genomic profile is defined as a patient with one or more actionable alteration 
where the patient qualifies to be screened for a COLOMATE companion trial based on 
the information recorded on the COLOMATE companion trial recommendation form.  
 
16.2 
Primary Endpoints 
 
There are two primary endpoints for this trial: 
 
• 
The first primary endpoint is “actionable genomic profile” defined as a patient who 
received a trial recommendation per the COLOMATE companion trial 
recommendation form. 
 
• 
The second primary endpoint is “companion trial enrollment” defined as a patient 
who has an actionable genomic profile that enrolls in their recommended companion 
trial. 
 
16.3 
Statistical Design 
 
This is a screening protocol and is not designed to test a specific hypothesis. All analyses 
will be done in descriptive fashion only.  
 
16.4  
Sample Size 
 
The total sample size of COLOMATE will be approximately 500 patients. The sample 
size for each individual companion trial will depend on the prevalence of the actionable 
genomic alterations and availability of companion trials. 
 
For ACCRU-GI-1611, there is no formal hypothesis testing.   
 
Given 500 patients, assume X% of patients can be assigned to a companion trial, the 
corresponding 95% confidence interval is shown in the table below.  The sample size of 
500 allows us to have good precision (i.e. confidence interval width less than 10%) in 
estimating the proportion of patients recommended into a companion trial. 
Assumed proportion of patients can be 
recommended to a companion trial (X%) 
Confidence interval 
10% 
(7.37%, 12.63%) 
20% 
(14.49%, 23.51%) 

 
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30% 
(25.98%, 34.02%) 
40% 
(35.71%, 44.29%) 
50% 
(45.62%, 54.38%) 
60% 
(55.71%, 64.29%) 
 
Assume 40% of the patients will be recommended to a companion trial (i.e. N=200) and 
further assume X% of patients would enrolled into the recommended trial, the 
corresponding 95% confidence interval is shown in the table below.  With a sample size 
of 500 and 40% of patients recommended, we also have decent precision (i.e. confidence 
interval width less than 15%) in estimating the proportion of patients enrolled into the 
recommended trials among those recommended.  Given the fact that ACCRU-GI-1611 is 
actively opening additional companion trials, we do not expect less than 40% of patients 
will be recommended to a companion trial. 
 
Proportion of patients enrolled into the 
recommended companion trial (X%) 
Confidence interval 
5% 
(1.98%, 8.02%) 
10% 
(5.84%, 14.16%) 
15% 
(10.05%, 19.95%) 
20% 
(14.46%, 25.54%) 
25% 
(19.00%, 31.00%) 
30% 
(23.65%, 36.35%) 
 
 
16.5      Analysis Plan 
 
16.51 Primary Endpoints 
 
• 
For the analysis of the first primary endpoint, the proportion of patients who 
have an actionable genomic profile will be calculated. This is defined as the 
total number of eligible patients who have an actionable genomic profile 
divided by the total number of eligible patients whose genomic profile is 
available for COLOMATE steering committee review.  
 
A patient may come back to ACCRU-GI-1611 for subsequent screening (see 
sections 7.5, 7.5, and 7.6); therefore, a patient can contribute information to 
the first primary endpoint more than once. 
 
• 
Our goal is to have at least 20% of patients have actionable genomic profile. 
The endpoint will be presented as a point estimate along with a 95% 
confidence interval (by Wald asymptotic confidence limit). 
 
• 
For the analysis of the second primary endpoint, the proportion of patients 
that enroll in the companion trial recommended by the COLOMATE 
committee will be calculated. This is defined as the total number of eligible 
patients that enroll in the recommended companion trial divided by the total 
number of eligible patients who have an actionable genomic profile.   
 
A patient may come back to ACCRU-GI-1611 for subsequent screening (see 
sections 7.4, 7.5, and 7.6); therefore a patient can contribute information to 

 
17 
ACCRU-GI-1611 
Amendment 2 
 
the second primary endpoint more than once. 
 
• 
Our goal is to enroll at least 75% of patients who have an actionable genomic 
profile. The endpoint will be presented as a point estimate along with a 95% 
confidence interval (by Wald asymptotic confidence limit). 
 
 
17.0 
Pathology Considerations/Tissue Biospecimens  
 
 As specific future analyses are identified, this protocol may be amended and IRB approval 
obtained. 
 
18.0 
Records and Data Collection Procedures 
 
18.1 Submission Timetable 
 
Initial Material(s) 
CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule Section 4) 
Institutional Contacts 
30 days (±3 days) after registration 
On-Study  
Supporting Documentation: Baseline1 
Specimen Submission: Blood - Baseline 
(see Section 14)2 
Patient Status: Baseline 
1.   Pathology report confirming adenocarcinoma, all available tumor molecular testing 
reports (KRAS, NRAS, BRAF, MSI-H, etc.), Guardant360 test results, and 
COLOMATE Companion Trial Recommendation Form. 
2.   Submit if Guardant360 (cfDNA) test is done after registration to COLOMATE. 
 
 
 
 
 
 
 
Test Schedule Material(s)  
CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule Section 4) 
At Receipt of  
Guardant360 Testing 
At any 
occurrence 
Consent Withdrawal1 
 
X 
Consent Withdrawal: Specimen Only1 
 
X 

 
18 
ACCRU-GI-1611 
Amendment 2 
 
CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule Section 4) 
At Receipt of  
Guardant360 Testing 
At any 
occurrence 
Deviation Form1 
 
X 
DNA Testing Dates (Internal Use Only-
ACCRU Office) 
 
X 
1. Submit only if applicable. 
 
 
19.0 
Budget 
 
19.1 
Each site should review the test schedule (Section 4), taking into account local and 
regional coverage policies, to determine which items are standard of care and which are 
research at their site. Refer to the payment synopsis for funding provided per accrual for 
covering study costs, as well as any additional invoiceables that may be allowed. 
 
19.2 
Tests to be research funded: 
 
• 
Guardant360 cfDNA testing at baseline 
 
19.3 
Other budget concerns: Refer to the payment synopsis for funding provided for covering 
any costs, as well as any additional invoiceables that may be allowed.  
 
20.0 
References 
 
Arena, S., B. Bellosillo, G. Siravegna, A. Martinez, I. Canadas, L. Lazzari, N. Ferruz, M. Russo, 
S. Misale, I. Gonzalez, M. Iglesias, E. Gavilan, G. Corti, S. Hobor, G. Crisafulli, M. Salido, J. 
Sanchez, A. Dalmases, J. Bellmunt, G. De Fabritiis, A. Rovira, F. Di Nicolantonio, J. Albanell, 
A. Bardelli and C. Montagut (2015). "Emergence of Multiple EGFR Extracellular Mutations 
during Cetuximab Treatment in Colorectal Cancer." Clin Cancer Res 21(9): 2157-2166. 
 
Bettegowda, C., M. Sausen, R. J. Leary, I. Kinde, Y. Wang, N. Agrawal, B. R. Bartlett, H. Wang, 
B. Luber, R. M. Alani, E. S. Antonarakis, N. S. Azad, A. Bardelli, H. Brem, J. L. Cameron, C. C. 
Lee, L. A. Fecher, G. L. Gallia, P. Gibbs, D. Le, R. L. Giuntoli, M. Goggins, M. D. Hogarty, M. 
Holdhoff, S. M. Hong, Y. Jiao, H. H. Juhl, J. J. Kim, G. Siravegna, D. A. Laheru, C. Lauricella, 
M. Lim, E. J. Lipson, S. K. Marie, G. J. Netto, K. S. Oliner, A. Olivi, L. Olsson, G. J. Riggins, A. 
Sartore-Bianchi, K. Schmidt, M. Shih l, S. M. Oba-Shinjo, S. Siena, D. Theodorescu, J. Tie, T. T. 
Harkins, S. Veronese, T. L. Wang, J. D. Weingart, C. L. Wolfgang, L. D. Wood, D. Xing, R. H. 
Hruban, J. Wu, P. J. Allen, C. M. Schmidt, M. A. Choti, V. E. Velculescu, K. W. Kinzler, B. 
Vogelstein, N. Papadopoulos and L. A. Diaz, Jr. (2014). "Detection of circulating tumor DNA in 
early- and late-stage human malignancies." Sci Transl Med 6(224): 224ra224. 
 
 
Corcoran, R. B., H. Ebi, A. B. Turke, E. M. Coffee, M. Nishino, A. P. Cogdill, R. D. Brown, P. 
Della Pelle, D. Dias-Santagata, K. E. Hung, K. T. Flaherty, A. Piris, J. A. Wargo, J. Settleman, 
M. Mino-Kenudson and J. A. Engelman (2012). "EGFR-mediated re-activation of MAPK 

 
19 
ACCRU-GI-1611 
Amendment 2 
 
signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with 
vemurafenib." Cancer Discov 2(3): 227-235. 
 
Diaz, L. A., Jr., R. T. Williams, J. Wu, I. Kinde, J. R. Hecht, J. Berlin, B. Allen, I. Bozic, J. G. 
Reiter, M. A. Nowak, K. W. Kinzler, K. S. Oliner and B. Vogelstein (2012). "The molecular 
evolution of acquired resistance to targeted EGFR blockade in colorectal cancers." Nature 
486(7404): 537-540. 
 
Gerlinger, M., A. J. Rowan, S. Horswell, J. Larkin, D. Endesfelder, E. Gronroos, P. Martinez, N. 
Matthews, A. Stewart, P. Tarpey, I. Varela, B. Phillimore, S. Begum, N. Q. McDonald, A. Butler, 
D. Jones, K. Raine, C. Latimer, C. R. Santos, M. Nohadani, A. C. Eklund, B. Spencer-Dene, G. 
Clark, L. Pickering, G. Stamp, M. Gore, Z. Szallasi, J. Downward, P. A. Futreal and C. Swanton 
(2012). "Intratumor heterogeneity and branched evolution revealed by multiregion sequencing." 
N Engl J Med 366(10): 883-892. 
 
Janku, F., H. J. Huang, B. Claes, G. S. Falchook, S. Fu, D. Hong, N. M. Ramzanali, G. Nitti, G. 
Cabrilo, A. M. Tsimberidou, A. Naing, S. A. Piha-Paul, J. J. Wheler, D. D. Karp, V. R. Holley, R. 
G. Zinner, V. Subbiah, R. Luthra, S. Kopetz, M. J. Overman, B. K. Kee, S. Patel, B. Devogelaere, 
E. Sablon, G. Maertens, G. B. Mills, R. Kurzrock and F. Meric-Bernstam (2016). "BRAF 
Mutation Testing in Cell-Free DNA from the Plasma of Patients with Advanced Cancers Using a 
Rapid, Automated Molecular Diagnostics System." Mol Cancer Ther. 
 
Jemal, A., R. Siegel, J. Xu and E. Ward (2010). "Cancer statistics, 2010." CA: A Cancer Journal 
for Clinicians 60(5): 277-300. 
 
Kim, S. T., W. S. Lee, R. B. Lanman, S. Mortimer, O. A. Zill, K. M. Kim, K. T. Jang, S. H. Kim, 
S. H. Park, J. O. Park, Y. S. Park, H. Y. Lim, H. Eltoukhy, W. K. Kang, W. Y. Lee, H. C. Kim, 
K. Park, J. Lee and A. Talasaz (2015). "Prospective blinded study of somatic mutation detection 
in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid 
tumor patients." Oncotarget. 
 
Kopetz, S., J. Desai, E. Chan, J. R. Hecht, P. J. O'Dwyer, D. Maru, V. Morris, F. Janku, A. 
Dasari, W. Chung, J. P. Issa, P. Gibbs, B. James, G. Powis, K. B. Nolop, S. Bhattacharya and L. 
Saltz (2015). "Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated 
Colorectal Cancer." J Clin Oncol 33(34): 4032-4038. 
 
Le, D. T., J. N. Uram, H. Wang, B. R. Bartlett, H. Kemberling, A. D. Eyring, A. D. Skora, B. S. 
Luber, N. S. Azad, D. Laheru, B. Biedrzycki, R. C. Donehower, A. Zaheer, G. A. Fisher, T. S. 
Crocenzi, J. J. Lee, S. M. Duffy, R. M. Goldberg, A. de la Chapelle, M. Koshiji, F. Bhaijee, T. 
Huebner, R. H. Hruban, L. D. Wood, N. Cuka, D. M. Pardoll, N. Papadopoulos, K. W. Kinzler, S. 
Zhou, T. C. Cornish, J. M. Taube, R. A. Anders, J. R. Eshleman, B. Vogelstein and L. A. Diaz, Jr. 
(2015). "PD-1 Blockade in Tumors with Mismatch-Repair Deficiency." N Engl J Med 372(26): 
2509-2520. 
 
Mao, M., F. Tian, J. M. Mariadason, C. C. Tsao, R. Lemos, Jr., F. Dayyani, Y. N. Gopal, Z. Q. 
Jiang, Wistuba, II, X. M. Tang, W. G. Bornman, G. Bollag, G. B. Mills, G. Powis, J. Desai, G. E. 
Gallick, M. A. Davies and S. Kopetz (2013). "Resistance to BRAF inhibition in BRAF-mutant 
colon cancer can be overcome with PI3K inhibition or demethylating agents." Clin Cancer Res 
19(3): 657-667. 
 
Meric-Bernstam, F., L. Brusco, K. Shaw, C. Horombe, S. Kopetz, M. A. Davies, M. Routbort, S. 

 
20 
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A. Piha-Paul, F. Janku, N. Ueno, D. Hong, J. De Groot, V. Ravi, Y. Li, R. Luthra, K. Patel, R. 
Broaddus, J. Mendelsohn and G. B. Mills (2015). "Feasibility of Large-Scale Genomic Testing to 
Facilitate Enrollment Onto Genomically Matched Clinical Trials." J Clin Oncol. 
 
Morelli, M. P., M. J. Overman, A. Dasari, S. M. A. Kazmi, E. V. Sanchez, C. Eng, B. K. Kee, L. 
Deaton, C. R. Garrett, F. Diehl, P. Angenendt and S. Kopetz (2013). "Heterogeneity of acquired 
KRAS and EGFR mutations in colorectal cancer patients treated with anti-EGFR monoclonal 
antibodies." J Clin Oncol 31(suppl; abstr 3512). 
 
Morelli, M. P., M. J. Overman, E. V. Sanchez, V. K. Morris, I. Shureiqi, C. R. Garrett, D. R. 
Fogelman, K. P. S. Raghav, B. K. Kee, L. Deaton, C. Eng, R. A. Wolff, D. Sebisanovic, L. M. 
Siew, A. Zapanta, G. Mei, B. Schiller, H. Eltoukhy, A. A. Talasaz and S. Kopetz (2014). 
"Frequency of concurrent gene mutations and copy number alterations in circulating cell-free 
DNA (cfDNA) from refractory metastatic CRC patients." J Clin Oncol 32(5s): suppl; abstr 11117. 
 
Oliner, K. S., J.-Y. Douillard, S. Salvatore, J. Tabernero, R. L. Burkes, M. E. Barugel, Y. 
Humblet, G. Bodoky, D. Cunningham, J. Jassem, F. Rivera, I. Kocáková, P. Ruff, M. Blasinska-
Morawiec, M. Smakal, R. T. Williams, A. Rong, J. S. Wiezorek, R. Sidhu and S. D. Patterson 
(2013). "Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of 
panitumumab (pmab) plus FOLFOX versus FOLFOX as first-line treatment (tx) for metastatic 
colorectal cancer (mCRC)." J Clin Oncol 31(suppl; abstr 3511). 
 
Sacher, A. G., C. Paweletz, S. E. Dahlberg, R. S. Alden, A. O'Connell, N. Feeney, S. L. Mach, P. 
A. Janne and G. R. Oxnard (2016). "Prospective Validation of Rapid Plasma Genotyping for the 
Detection of EGFR and KRAS Mutations in Advanced Lung Cancer." JAMA Oncol. 
 
Strickler, J. H., T. Zhang, A. J. Armstrong, D. Niedzwiecki, H. E. Uronis, M. A. Morse, S. Y. 
Zafar, S. D. Hsu, C. Arrowood, R. Nagy, A. Talasaz, R. B. Lanman, S. Haley and H. I. Hurwitz 
(2015). "Cell free DNA (cfDNA) to monitor clonal evolution in patients (pts) with KRAS wild-
type (WT) metastatic colorectal cancer (mCRC): Preliminary results of a phase I/II clinical trial 
of the anti-MET multi-kinase inhibitor cabozantinib (C) plus the anti-EGFR monoclonal antibody 
panitumumab (P)." Mol Cancer Ther 14(12 Suppl 2: Abstract nr A52). 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 1 of 12 
 
Appendix I: ACCRU Informed Consent Template for 
ACCRU-GI-1611 
(English Language) 
 
*NOTES FOR LOCAL INVESTIGATORS: 
• 
The goal of the informed consent process is to provide people with sufficient information 
for making informed choices. The informed consent form provides a summary of the 
clinical study and the individual's rights as a research participant. It serves as a starting 
point for the necessary exchange of information between the investigator and potential 
research participant. This template for the informed consent form is only one part of the 
larger process of informed consent.  
• A blank line, __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks. Check with your 
local IRB regarding review of additional materials. 
 
* These notes for {authors and} investigators are instructional and should not be included in 
the informed consent form given to the prospective research participant.  
 
This model informed consent form has been reviewed by the ACCRU and is the official consent 
document for this study. Local IRB changes to this document are allowed. Sections “What are 
the risks of the research study” or “What other choices do I have if I don’t take part in this 
research study?” should always be used in their entirety if possible. Editorial changes to these 
sections may be made as long as they do not change information or intent. If the institutional IRB 
insists on making deletions or more substantive modifications to these sections, they may be 
justified in writing by the investigator and approved by the IRB. Under these circumstances, the 
revised language and justification must be forwarded to the Academic and Community Cancer 
Research United (ACCRU) Operations Office for approval before a patient may be registered to 
this study. 
 
Consent forms will have to be modified for each institution as it relates to where information 
may be obtained on the conduct of the study or research subject. This information should be 
specific for each institution. 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 2 of 12 
 
Study Title: COLOMATE: COlorectal Cancer Liquid BiOpsy Screening Protocol for 
Molecularly Assigned ThErapy 
 
IRB#:  
{institutional IRB number} 
 
Principal Investigator: {Site PI} and Colleagues 
 
Please read this information carefully. It tells you important things about this research study. A 
member of our research team will talk to you about taking part in this research study. If you have 
questions at any time, please ask us. 
 
Take your time to decide. Feel free to discuss the study with your family, friends, and healthcare 
provider before you make your decision.  
 
To help you decide if you want to take part in this study, you should know: 
 
• Taking part in this study is completely voluntary.  
• You can choose not to participate.  
• You are free to change your mind at any time if you choose to participate.  
• Your decision won’t cause any penalties or loss of benefits to which you’re otherwise 
entitled. 
• Your decision won’t change the access to medical care you get at {institution} now or in 
the future if you choose not to participate or discontinue your participation. 
 
If you decide to take part in this research study, you will sign this consent form to show that you 
want to take part. We will give you a copy of this form to keep. A copy of this form will be put 
in your medical record. 
 
If you are signing this consent form for someone else, “you” in the consent form refers to the 
participant. 
 
 

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Appendix I 
Amendment 2 
Page 3 of 12 
 
 
CONTACT INFORMATION 
 
 
{Note to Local Investigator: Contact information for patient representatives or other individuals 
in a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can be listed here.} 
 
You can contact … 
At … 
If you have questions about … 
Principal 
Investigator(s): 
 
 
Study Team Contact: 
 
 
 
Phone: 
 
 
Phone: 
 
 
Institution Name and Address: 
 
 
 Study tests and procedures 
 Research-related injuries or 
emergencies 
 Any research-related concerns or 
complaints 
 Withdrawing from the research study 
 Materials you receive 
 Research-related appointments 
Institutional Review 
Board (IRB) 
Phone: 
 
Toll-Free: 
 
 Rights of a research participant 
 
Research Subject 
Advocate 
(The RSA is independent 
of the Study Team) 
Phone: 
 
Toll-Free: 
 
E-mail: 
 
 Rights of a research participant 
 Any research-related concerns or 
complaints 
 Use of your Protected Health 
Information 
 Stopping your authorization to use 
your Protected Health Information 
Research Billing 
 
 Billing or insurance related to this 
research study 
 
Other Information: 
 
A description of this clinical trial will be available on 
 as required 
by U.S. Law. This Website will not include information that can identify you. At most, the 
Website will include a summary of the results. You can search this Website at any time. 
 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 4 of 12 
 
 
1. 
Why are you being asked to take part in this research study? 
 
 
You are being asked to take part in this research study because you have adenocarcinoma of the 
colon or rectum that is spreading to other parts of the body and/or cannot be removed completely 
through surgery.  
 
 
2. 
Why is this research study being done? 
 
 
The purpose of this research study is to use a blood test to find out what mutations your cancer 
cells might have. We would like to use this information to see if there is a research study 
available that may target these mutations.  
 
 
 
3. 
Information you should know 
 
 
Who is Funding the Study? 
 
This study is funded by an anonymous philanthropic donor, a foundation grant from Mayo 
Clinic, and by Guardant Health. 
 
 
Information Regarding Conflict of Interest: 
 
{Insert any institution- /investigator-specific financial conflict language} 
 
Your healthcare provider may be referring you to this research study. If your healthcare provider 
is also an investigator on this study, there is the chance that his or her responsibilities for the 
study could influence his or her recommendation for your participation. If you prefer, your 
healthcare provider will be happy to refer you to another investigator on the research study team 
for you to decide if you want to participate in the study and to see you for the research study 
activities while you are in the study 
 
 
How Many People Will Take Part in the Research Study? 
 
About 500 people will take part in this study.  
 
 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 5 of 12 
 
 
 
 
 
What are my rights if I take part in this research study? 
 
Taking part in this study is your choice. You may choose either to take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No matter 
what decision you make, there will be no penalty to you and you will not lose any of your regular 
benefits. Leaving the study will not affect your medical care. You can still get your medical care 
from our institution.  
 
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.  
 
 
Where can I get more information? 
 
You may call the National Cancer Institute's Cancer Information Service at:  
 
  
 
You may also visit the NCI Web site at 
 
 
• For NCI’s clinical trials information, go to: 
 
 
• For NCI’s general information about cancer, go to 
 
 
You will get a copy of this form. If you want more information about this study, ask your study 
doctor. 
 
 
 
4. 
How long will you be in this research study? 
 
 
You will only be in this research study for the time it takes to have the research blood test drawn 
and for the results to come back. Your study team will contact you by phone 30 days after the 
date you go on study to ask you which, if any, research trial you enrolled on after receiving the 
recommendations given to you based on your blood test results.    
 
 
 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 6 of 12 
 
 
5. 
What will happen to you while you are in this research study? 
 
 
Before you begin the study: 
 
You will need to have the following exams, tests or procedures to find out if you can be in the 
study. These exams, tests or procedures are part of regular cancer care and may be done even if 
you do not join the study. If you have had some of them recently, they may not need to be 
repeated. 
 
• 
Demographics 
• 
Medical and cancer history 
• 
Physical examination 
• 
Height 
• 
Weight 
• 
Vital signs 
• 
ECOG performance status 
 
During the study: 
 
You will need the following test and evaluation. 
 
• 
Cell-free DNA blood test (Guardant360 testing). If you have completed this 
blood test ≤60 days prior to this study, you can fill out an authorization form to 
release the results to the study team and will not need to complete this test again. 
Your demographic information will be collected on the form to send in the blood 
test and also on the authorization form to release previous results. Your 
demographic information will be sent to Guardant Health, Inc. and will only be 
used for the purposes of the Guardant360 blood test. Your demographic 
information will not be used to conduct this study nor will it be shared outside of 
Guardant Health, Inc. 
• 
Follow-up phone call 30 days after you enroll on this study. 
 
 
Study Chart 
 
Day 
What you do 
Before starting 
study 
• Get routine exams and testing 
Day 1 
• Sign consent 
Between Day 1 
and Day 30 
• Get research blood test 
Within 2-3 
weeks 
• Get blood test results and list of any available trials 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 7 of 12 
 
30 days after 
starting study 
• You will receive a follow-up phone call from your study team 
 
 
Study Plan 
 
Another way to find out what will happen to you during the study is to read the chart below. Start 
reading at the top and read down the list, following the lines and arrows. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Research test results 
Research blood test 
Sign informed consent form 
Routine exams and tests 
Start Here 
Phone Call with Nurse/CRA 
Off Study 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 8 of 12 
 
Selection Process 
 
The results of your Guardant 360 blood test will be reviewed by the COLOMATE review 
committee.  The committee will review any mutations found by the test and provide 
recommendations to which companion trial you may be eligible for based on these mutations.  
The associated companion trials involve receiving drug regimens that target different mutations, 
including but not limited to, RAS wild-type, FGFR alterations, or HER 2 positive tumors.  If you 
are found to be a match to one these trials, your treating physician will be notified and will 
provide your information to the appropriate companion trial study team.  You will then be 
provided information on the trial you matched with and be provided the option to begin 
screening for the trial if you so choose.   
 
 
 
6. 
What are the possible risks or discomforts from being in this research 
study? 
 
 
Blood draw risk 
 
The risks of drawing blood include pain, bruising, lightheadedness, and/or fainting, or rarely, 
infection at the site of the needle stick. 
 
Confidentiality risk 
 
As with all research, there is a chance that confidentiality could be compromised; however, we 
take precautions to minimize this risk. 
 
Genetic testing risk 
 
This study involves testing your DNA, which is the genetic information you inherited from your 
parents (also known as genetic testing). The risks of learning genetic test results may include 
emotional upset, insurance or job discrimination, and/or changes in family relationships because 
test results may affect other blood relatives. 
 
A Federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes 
it illegal for health insurance companies, group health plans, and most employers to discriminate 
against you based on your genetic information. This law generally will protect you in the 
following ways:  
 
• Health insurance companies and group health plans may not request your genetic 
information that we get from this research.  
• Health insurance companies and group health plans may not use your genetic 
information when making decisions regarding your eligibility or premiums.  

ACCRU-GI-1611 
Appendix I 
Amendment 2 
Page 9 of 12 
 
• Employers with 15 or more employees may not use your genetic information 
when making a decision to hire, promote, or fire you or when setting the terms of 
your employment.  
 
All health insurance companies and group health plans must follow this law.  
 
Be aware that this new Federal law doesn’t protect you against genetic discrimination by 
companies that sell life insurance, disability insurance, or long-term care insurance. 
 
 
 
7. 
Are there reasons you might leave this research study early? 
 
 
Yes, you can decide to stop at any time. Tell the study doctor if you are thinking about stopping 
or decide to stop.  
 
It is important to tell the study doctor if you are thinking about stopping so any risks can be 
evaluated by your doctor. Another reason to tell your doctor that you are thinking about stopping 
is to discuss what follow-up care and testing could be most helpful for you. 
 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest; if you do not follow the study rules; or if the study is stopped. 
 
 
 
8. 
What if you are injured from your participation in this research study? 
 
 
Where to get help: 
 
It is important that you tell your study doctor, {investigator’s name(s)}, if you feel that you have 
been injured because of taking part in this study. You can tell the doctor in person or call him/her 
at {telephone number}. 
 
 
Who will pay for the treatment of research related injuries? 
 
You will get medical treatment if you are injured as a result of taking part in this study. You 
and/or your health plan will be charged for this treatment. The study will not pay for medical 
treatment. 
 
 
 
9. 
What are the possible benefits from being in this research study? 
 

ACCRU-GI-1611 
Appendix I 
Amendment 2 
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Taking part in this study may not make your health better. However, the doctors hope that results 
of the research test will help identify other research trials that you might be eligible for to treat 
your cancer. 
 
 
 
10. 
What alternative do you have if you choose not to participate in this 
research study? 
 
 
This study is only being done to gather information. You may choose not to take part in this 
study. 
 
 
 
11. 
What tests or procedures will you need to pay for if you take part in this 
research study?  
 
 
You and/or your health plan/ insurance company will need to pay for some of the costs of 
screening for your cancer prior to enrolling in this study. Some health plans will not pay these 
costs for people taking part in studies. Check with your health plan or insurance company to find 
out what they will pay for. Taking part in this study may or may not cost your insurance 
company more than the cost of getting regular cancer treatment. 
 
Guardant Health is covering the cost of the research blood test. 
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at 
coverage. You can 
print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. 
 
Another way to get the information is to call 
and ask them 
to send you a free copy. 
 
 
 
12. 
Will you be paid for taking part in this research study? 
 
 
You will not be paid for taking part in this study. 
 
 
 
13. 
What will happen to your samples? 

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Appendix I 
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Your samples will be used for this study to perform cell-free DNA testing. When the testing is 
done, any remaining sample will be kept for quality assurance but no further research testing will 
be performed. 
 
If you choose to be evaluated for a research study available that may target the mutations your 
cancer might have, the data that we receive from the blood test results will be sent to the 
appropriate study team.  
 
The data that we receive from the blood test results may be used for future research that may 
help people who have cancer and other health problems (for example: diabetes, Alzheimer’s 
disease, or heart disease).  
 
In the future, people who do research outside of ACCRU may need to know more about your 
health. While ACCRU may give them reports about your health, it will not give them your name, 
address, phone number, or any other information that will let the researchers know who you are.  
 
The data will be used only for research and will not be sold.  The research done with your data 
may help to develop new products in the future.  
 
 
 
14. 
How will your privacy and the confidentiality of your records be protected? 
 
 
We will do our best to make sure that the personal information in your medical record will be 
kept private. However, we cannot guarantee total privacy. Your personal information may be 
given out if required by law. If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used.  
 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
 
• The local and/or central IRB that oversees the research 
• Other {institution} physicians involved in your clinical care  
• Duke University 
• Mayo Clinic 
• Guardant Health 
• National Cancer Center Hospital 
• Yokohama City University 
• National Cancer Hospital East, Japan 
• University of Chicago 
• Government agencies, like the Food and Drug Administration (FDA), involved in 
keeping research safe for people 

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{Note to Local Investigators: The NCI has recommended that HIPAA regulations be addressed 
by the local institution. The regulations may or may not be included in the informed consent form 
depending on local institutional policy.} 
 
During this research, information about your health will be collected. Under Federal law called 
the Privacy Rule, health information is private. However, there are exceptions to this rule, and 
you should know who may be able to see, use and share your health information for research and 
why they may need to do so. Information about you and your health cannot be used in this 
research study without your written permission. If you sign this form, it will provide that 
permission.  
 
 
Health information may be collected about you from: 
 
• Past, present and future medical records 
• Research procedures, including research office visits, tests, interviews and questionnaires 
 
 
Why will this information be used and/or given to others? 
 
• To do the research 
• To report the results 
• To see if the research was done correctly 
 
If the results of this study are made public, information that identifies you will not be used. 
 
 
Is your health information protected after it has been shared with others? 
 
{Institution} asks anyone who receives your health information from us to protect your privacy; 
however, once your information is shared outside {Institution}, we cannot promise that it will 
remain private and it may no longer be protected by the Privacy Rule. 
 
 
Your Privacy Rights 
 
You do not have to sign this form, but if you do not, you cannot take part in this research study. 
 
If you cancel your permission to use or share your health information, your participation in this 
study will end and no more information about you will be collected; however, information 
already collected about you in the study may continue to be used. 
 
If you choose not to take part or if you withdraw from this study, it will not harm your 
relationship with your own doctors or with {Institution}. 
 

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Appendix I 
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You can cancel your permission to use or share your health information at any time by {note 
instructions for canceling consent}: 
 
Your permission lasts until the end of this study, unless you cancel it. Because research is an 
ongoing process, we cannot give you an exact date when the study will end. 
 
 
 
 
 
 
 
 
 
 
 
 
 
ENROLLMENT AND PERMISSION SIGNATURES 
 
 
Your signature documents your permission to take part in this research. 
 
 
 
  
 
 
 
/ / 
 
 
 
 : 
 AM/PM  
Printed Name  
 
 
 
Date 
 
 
 
Time   
 
 
 
 
_______________________________ 
Signature 
 
 
Person Obtaining Consent 
• I have explained the research study to the participant. 
• I have answered all questions about this research study to the best of my ability. 
 
 
 
  
 
 
 
/ / 
 
 
 
 : 
 AM/PM  
Printed Name  
 
 
 
Date 
 
 
 
Time   
 
 
_______________________________ 
Signature