Clinical trial NCT03892096: Development of a Cell Free DNA Assay as a Biomarker for Predicting Early Non-response to Therapy in Metastatic Cancer
Official title: Development of a Cell Free DNA Assay as a Biomarker for Predicting Early Non-response to Therapy in Metastatic Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metastatic Non-Small Cell Lung Carcinoma
Metastatic Colorectal Cancer
Metastatic Breast Cancer
Lead sponsor: Cadex Genomics
Sponsor class: INDUSTRY
First posted: 2019-03-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: A total of 750 subjects with Lung Cancer, CRC or BC will be enrolled consecutively into each cancer group. It is expected that each group will enroll 250 subjects each. As each group meets its enrollment goals, that group will close to further enrollment.

Brief summary: Accrue samples for the further development and clinical validation of a blood-based cell-free DNA (cfDNA) quantitative real-time polymerase chain reaction (qPCR) assay as a potential biomarker for early non-response to therapy in stage IV non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer (BC).

Detailed description: Most anticancer drugs are effective only in subgroups of patients, and our current understanding of tumor biology does not allow us to predict accurately which patient will benefit from a specific therapeutic regimen. The definitive proof of the effectiveness of a therapy is improvement in clinical symptoms and survival. Imaging is generally used to assess therapeutic effects earlier and more objectively. Current response assessment is based primarily on changes in tumor size as measured by CT or other anatomic imaging modalities.

Cadex Genomics has developed an analytically validated cell-free DNA (cfDNA) quantitative real-time polymerase chain reaction (qPCR) assay that utilizes standard qPCR platforms for processing, this test can reliably obtain results from small blood volumes and possesses exceptionally high analytical sensitivity of circulating cfDNA.

The purpose of this study is to accrue samples for the further development and clinical validation of a blood-based cell-free cfDNA qPCR assay as a potential biomarker for early non-response to therapy in stage IV non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer (BC).

Eligibility criteria: Inclusion Criteria:

Age ≥ 18 years.

Documented stage IV NSCLC, SCLC, BC or CRC (can be new diagnosis, persistent or recurrent disease):

BC patients who meet the following criteria:

ER+/HER2- and has failed hormone therapy within the last two years, or ER+/HER2+ or, ER-/HER+ or, HER2-/ER-/PR- (TNBC), and Has ≥ 1 measurable non- bone lesion as measured per RECIST or, If bone only disease, has two or more measurable (\> 1 cm by RECIST) predominantly lytic bone lesions

Planned initiation of new systemic first- or second-line treatment or subsequent therapies with chemotherapy, immunotherapy, targeted therapy or combination thereof. Or continuation of the current line of therapy after RECIST/iRECIST evaluation which coincides with end of the cycle of therapy and prior to initiation of the next cycle of therapy.

Imaging to determine RECIST and/or iRECIST criteria:

If baseline blood draw is planned prior to first cycle of a line (1st, 2nd, 3rd etc) of therapy, measurable disease with CT or MRI or PET/CT monitoring should be completed within 4 weeks prior to baseline blood draw.

If baseline test is performed at the completion of a cycle of therapy, CT or MRI or PET/CT monitoring should be completed to coincide with end of cycle of therapy and prior to baseline blood draw.

Planned CT or MRI or PET/CT monitoring for treatment response completed within 8-12 weeks of start of treatment.

Willing and able to donate up to 30mL of blood at each blood draw. Willing and able to provide informed consent.

Exclusion Criteria:

Diagnosis of a secondary malignancy that is not in complete remission. Imaging to determine RECIST and/or iRECIST criteria is not planned or available.

CT or MRI or PET/CT monitoring for treatment response is not planned within 8-12 weeks.

Presence of active autoimmune disease which is under active treatment. DVT, PE, sepsis, or has recovered from any other serious illness within the prior 2 weeks of the baseline blood draw. (Note: Patients who have recovered from similar conditions more than 2 weeks prior to the baseline blood draw would be eligible for the study) If initiating a new line of therapy, patient has received any doses of the new block of therapy before the first designated blood draw.

If continuing current line of therapy after CT, MRI or PET/CT monitoring, patient has received subsequent cycle of therapy before the first designated blood draw.

Performance status ECOG ≥3. Evidence of acute renal failure as determined by current clinical guidelines. NSCLC, SCLC or CRC patients beyond 9 months of the initiation of therapy, on 1st line immunotherapy alone, or combination immunotherapy and chemotherapy regimens. (Note: patients on subsequent lines of therapy (2nd,3rd line etc.) would be eligible at any time point including prior to the 9 months vs those patients on 1st line therapy)..

Primary outcomes:
measure: DNA Integrity Index as a predictor of progressive disease in a cohort of metastatic patients (250 Lung Cancer (NSCLC, SCLC), 250 CRC and 250 BC patients as compared to standard RECIST/iRECIST criteria.
timeFrame: Six months to accrue patient for initial development
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: CARTI Cancer Center
state: Arkansas
city: Sunnyvale
country: United States
facility: Sutter Health - Palo Alto Medical Foundation
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: New Orleans
country: United States
facility: University Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Southeast Louisiana Veterans Health Care System
state: Louisiana
city: Omaha
country: United States
facility: Nebraska Cancer Center
state: Nebraska
city: Port Jefferson Station
country: United States
facility: National Translational Research Group LLC
state: New York
city: Cary
country: United States
facility: Waverly Hematology Oncology
state: North Carolina
city: Hendersonville
country: United States
facility: Advent Health
state: North Carolina
city: Greenville
country: United States
facility: Greenville Health System - Prisma Health
state: South Carolina
city: Montréal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Cadex Genomics
name: Christer Svedman, M.D. Ph.D.
role: STUDY_DIRECTOR
References: