EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer
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| ClinicalTrials.gov Identifier: NCT06011772 |
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Recruitment Status :
Recruiting
First Posted : August 25, 2023
Last Update Posted : May 3, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Colo-rectal Cancer | Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine Drug: Leucovorin Drug: Oxaliplatin Drug: Fluorouracil Biological: Bevacizumab Drug: Irinotecan Biological: Cetuximab Procedure: Metastasectomy Procedure: Biospecimen collection Procedure: Computed Tomography Biological: Panitumumbab | Early Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 42 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 0 Study of EGF-Depleting Therapy CIMAvax-EGF in Combination With Standard Therapy for RAS- and BRAF Wild-Type Metastatic Colorectal Cancer |
| Actual Study Start Date : | December 4, 2023 |
| Estimated Primary Completion Date : | December 4, 2025 |
| Estimated Study Completion Date : | December 4, 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A1
LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV and bevacizumab IV over 10 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial. |
Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM
Other Names:
Drug: Leucovorin Given IV Drug: Oxaliplatin Given IV Drug: Fluorouracil Given IV Biological: Bevacizumab Given IV Procedure: Computed Tomography Undergo CT
Other Names:
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Experimental: Cohort B1
LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive FOLFIRI consisting of irinotecan IV, leucovorin IV over 90 minutes, and fluorouracil IV and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial. |
Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM
Other Names:
Drug: Leucovorin Given IV Drug: Fluorouracil Given IV Drug: Irinotecan Given IV Biological: Cetuximab Given IV Procedure: Biospecimen collection Undergo collection of blood samples |
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Experimental: Cohort B2
LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy and cetuximab IV over 120 minutes on days 1 and 15. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples throughout the trial |
Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM
Other Names:
Drug: Oxaliplatin Given IV Drug: Fluorouracil Given IV Biological: Cetuximab Given IV Procedure: Biospecimen collection Undergo collection of blood samples |
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Experimental: Cohort C
Description LOADING PHASE: Patients receive CIMAvax-EGF IM on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 and cetuximab, FOLFOX6 and bevacizumab, or mFOLFOX6 per investigators preference. Treatment repeats every 2 weeks for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo metastasectomy 4-8 weeks after first maintenance phase dose. Patients undergo collection of blood samples throughout the trial. |
Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM
Other Names:
Drug: Leucovorin Given IV Biological: Bevacizumab Given IV Biological: Cetuximab Given IV Procedure: Metastasectomy Undergo metastasectomy Procedure: Biospecimen collection Undergo collection of blood samples |
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Experimental: Cohort A2
LOADING PHASE: Patients receive CIMAvax-EGF intramuscularly (IM) on days 1 and 15. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive CIMAvax-EGF IM on day 15. Treatment repeats every 28 days for 10 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mFOLFOX6 chemotherapy consisting of leucovorin IV, oxaliplatin IV over 2 hours, and fluorouracil IV, as well as cetuximab IV over 120 minutes on days 1 and 15, or panitumumab IV over 60 minutes on days 1 and 15. Patients undergo collection of blood samples and CT throught the trial |
Biological: Recombinant Human EGF-rP64K/Montanide ISA 51 Vaccine
Given IM
Other Names:
Drug: Leucovorin Given IV Drug: Oxaliplatin Given IV Drug: Fluorouracil Given IV Procedure: Computed Tomography Undergo CT
Other Names:
Biological: Panitumumbab Given IV
Other Names:
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- Immunogencity of vaccine [ Time Frame: up to 60 days after last dose ]Percentage of patients with antibody titers greater than or equal to 1:4000 using a 90% confidence interval obtained by Jeffery's prior method
- Progression free survival [ Time Frame: time from treatment until disease progression, death or last follow up assesed up to 2 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically or cytologically confirmed metastatic adenocarcinoma of colon or rectum that cannot be removed by surgery without prior systemic therapy for advanced disease (prior adjuvant chemotherapy completed >12 months from diagnosis of metastatic or advanced disease is allowed) for cohorts A and C and with one prior line of therapy but no more than 2 prior lines of therapy for advanced disease (prior adjuvant chemotherapy completed <12 months from diagnosis of metastatic or advanced disease is considered one line of therapy).
- Cohort A: May have received 1 cycle of mFOLFOX6± Bevacizumab or mFOLFOX6± anti-EGFR therapy pending results of RAS and BRAF. If results determine patient is eligible, the patient will be enrolled and will receive the addition of CIMAvax + Bevacizumab or CIMAvax+ anti-EGFR therapy in their second cycle.
- Cohort B: Patients with RAS- and BRAF wild-type metastatic CRC who have received at least one but no more than 2 prior therapies for advanced disease
- Cohort C: Patients with RAS- and BRAF wild-type metastatic CRC who have not received prior therapy for advanced disease and are candidates for liver metastasectomy (one cycle of standard therapy with mFOLFOX6 with or without appropriate biologic agent is allowed)
- KRAS/NRAS/BRAF wild-type.
- Have an ECOG Performance Status of 0 1. Refer to Appendix A.
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Patients must have adequate organ and marrow function as defined below:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 8 g/dL
- Creatinine clearance> 60 mL/min (Cockcroft-Gault Equation)
- ALT and AST ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present
- Total bilirubin ≤ 1.5x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3x ULN with direct bilirubin within normal range
- Have measurable disease per RECIST 1.1 criteria present.
- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
- Participant agrees to provide tumor biopsy tissue while on study (cohort A and B) or allow tissue to be taken during surgery (cohort C)
Exclusion Criteria:
- Toxicity ≥Grade 2 from prior chemotherapy.
- Other cancer requiring active treatment.
- Prior exposure to anti-EGFR monoclonal antibody (i.e. cetuximab or panitumumab) for colorectal cancer treatment.
- Had major surgery within 4 weeks prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery.
- Has known immunosuppressive disease (e.g. HIV, AIDS or other immune depressing disease). Testing is not mandatory.
- Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Active, clinically serious infections or other serious uncontrolled medical conditions or psychiatric illness/social situations that would limit compliance with study requirements.
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History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to baseline or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease
- History of documented congestive heart failure (New York Heart Association functional classification III or IV) within 6 months prior to baseline
- Uncontrolled hypertension (SBP>160/DBP>100 despite medical intervention).
- History of myocarditis of any etiology
- History of ventricular arrhythmias
- Active major or clinically significant bleeding based on the International Society on Thrombosis and Hemostasis definition.
- Pregnant or nursing female participants.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06011772
| Contact: Deepak Vadehra | 716-845-2300 | askroswell@roswellpark.org |
| United States, New York | |
| Roswell Park Comprehensive Cancer Center | Recruiting |
| Buffalo, New York, United States, 14263 | |
| Principal Investigator: | Deepak Vadehra | Roswell Park Comprehensive Cancer Center |
| Responsible Party: | Roswell Park Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT06011772 |
| Other Study ID Numbers: |
I 1578122 |
| First Posted: | August 25, 2023 Key Record Dates |
| Last Update Posted: | May 3, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Leucovorin Bevacizumab Cetuximab Panitumumab |
Oxaliplatin Fluorouracil Irinotecan Vaccines Monatide (IMS 3015) Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action |