A Study of 1018 Immunostimulatory Sequence (ISS) Administered With Irinotecan and Cetuximab to Treat Patients With Previously Treated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The main objectives of this study are to establish a safe, tolerable and active dose of 1018 ISS administered in combination with irinotecan and cetuximab in patients with metastatic colorectal cancer. Other objectives also include determining tumor response, time to disease progression, and overall survival in treated patients.

Detailed Description
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This is a Phase I, open-label study of escalating dose levels of 1018 ISS in combination with irinotecan and cetuximab in patients with previously treated metastatic colorectal cancer. Approximately 15 patients will be treated. The objectives of this study are to establish a safe, tolerable, and active dose of 1018 ISS, determine tumor response, time to disease progression, and overall survival in treated patients. The safety and tolerability of 1018 ISS will be evaluated by periodic laboratory assessments, physical examinations, and compilation of adverse events. Once study patients have been consented, screened, and assigned to one of the dose levels of 1018 ISS, patients will receive two 4 week cycles of 1018 ISS therapy plus irinotecan every other week and cetuximab weekly. Irinotecan and cetuximab will continue thereafter until disease progression, unacceptable toxicity, or until the patient refuses treatment.

Official Title
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Phase 1 Study of the Combination of 1018 ISS, Irinotecan and Cetuximab in Patients With Metastatic Colorectal Cancer Previously Treated With a Fluoropyrimidine, Oxaliplatin or Irinotecan With or Without Bevacizumab

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: 1018 ISS immunostimulatory oligonucleotide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed, written, informed consent must be obtained from the patient or their legal representative before any study-specific procedures are performed Confirmed diagnosis of adenocarcinoma of the colon or rectum not amenable to curative surgery One or more prior systemic therapy regimens for metastatic cancer which must have included a fluoropyrimidine (5-fluorouracil (FU) by infusion or capecitabine), oxaliplatin or irinotecan with or without bevacizumab Exclusion Criteria: Clinically significant obstructive symptoms, intestinal bleeding, or chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom History of unstable or deteriorating cardiovascular or cerebrovascular disease within 3 months before the first dose of protocol therapy Clinical evidence of brain metastases or central nervous system disease Pregnant or lactating women Serious medical or psychiatric illness Malignancy other than colorectal carcinoma within the past 2 years, except curatively treated, superficial skin cancer or carcinoma in situ of the cervix Patients who have been on any experimental study or anti-tumor therapy, received radiotherapy, or had prior surgery (except venous access device placement) within 28 days before the first dose of protocol therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Low dose of 1018 ISS | Drug: 1018 ISS immunostimulatory oligonucleotide<br>* 6 weekly subcutaneous (under the skin) injections<br>|
| Experimental: 2<br>Middle dose of 1018 ISS | Drug: 1018 ISS immunostimulatory oligonucleotide<br>* 6 weekly subcutaneous (under the skin) injections<br>|
| Experimental: 3<br>High dose of 1018 ISS | Drug: 1018 ISS immunostimulatory oligonucleotide<br>* 6 weekly subcutaneous (under the skin) injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression |  | 9 or more weeks | 
| Overall survival time |  | 9 or more weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal, cancer, carcinoma, metastatic, colon, rectal, neoplasm, cetuximab, irinotecan, 1018 ISS, combination therapy