A Phase 2 interventional study of cetuximab and ramucirumab in Colorectal Cancer, sponsored by Eastern Cooperative Oncology Group. Completed at 255 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-06-28.
Sponsored by Eastern Cooperative Oncology Group · Phase 2, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and ramucirumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and ramucirumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet know whether giving cetuximab and irinotecan hydrochloride together is more effective with or without ramucirumab in treating colorectal cancer.
PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab and irinotecan hydrochloride with or without ramucirumab work in treating patients with advanced colorectal cancer with progressive disease after treatment with bevacizumab-containing chemotherapy.
OBJECTIVES:
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to performance status (0 vs 1), discontinuation of oxaliplatin before disease progression (yes vs no), and time to disease progression since last treatment (≤ 6 months vs > 6 months). Patients are randomized to 1 of 2 treatment arms.
In all arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically for 5 years.
5,599 studies on the registry are indexed under Colorectal Neoplasms; 1,459 are open to participants now.
This study's enrollment of 136 is above the median of 77 across 4,123 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Eastern Cooperative Oncology Group is the lead sponsor of 173 studies on the registry; 7 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 5 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients receive cetuximab (500 mg/m2) intravenously (IV) over 60-120 minutes and irinotecan hydrochloride (180 mg/m2) over 60-90 minutes on day 1. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.
Biological: cetuximab · Drug: irinotecan hydrochloride
Patients receive ramucirumab (8 mg/kg) IV over 60 minutes on day 1 and cetuximab and irinotecan hydrochloride as in arm A. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.
Biological: cetuximab · Biological: ramucirumab · Drug: irinotecan hydrochloride
Patients receive reduced dose of ramucirumab (6 mg/kg) IV over 60 minutes on day 1 and cetuximab (150 mg/m2) and irinotecan hydrochloride (400 mg/m2) as in arm B. Treatment repeats every 2 weeks until disease progression or unacceptable toxicities.
Biological: cetuximab · Biological: ramucirumab · Drug: irinotecan hydrochloride
Given IV
Also known as: IMC-C225, Erbitux®, NSC-714692
Given IV
Also known as: IMC 1121B, 1121B
Given IV
Also known as: Irinotecan hydrochloride trihydrate
Progression-free Survival
Progression-fee survival is defined as the time from randomization to disease progression or death without documentation of progression. Censoring occurred at the date of last disease assessment without progression for cases without documentation of progression, except for cases where death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was considered an event. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Proportion of Participants With an Objective Response Rate (CR or PR)
Objective response is defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
Proportion of Patients With Grade 3 or Higher Treatment-related Adverse Events
Adverse events were assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE). Treatment-related adverse events are defined as those that are possibly, probably, or definitely related to protocol therapy.
Time frame: Assessed every 2 weeks while on treatment and for 30 days after the end of treatment
Overall Survival
Overall survival is defined as the time from randomization to death or date last known alive.
Time frame: Assessed every 3 months for 2 years, every 6 months for the 3rd year, then annually up to 5 years
The first patient was accrued on January 18, 2011.
| Milestone | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Started | 70 | 16 | 50 |
| Started protocol therapy | 69 | 16 | 48 |
| Treated patients with toxicity data available | 68 | 16 | 48 |
| Eligible and treated | 62 | 16 | 45 |
| Analyzable patients for efficacy analysis | 44 | 0 | 45 |
| Completed | 0 | 0 | 0 |
| Not completed | 70 | 16 | 50 |
| Withdrew: Disease progression | 43 | 7 | 31 |
| Withdrew: Adverse event | 13 | 5 | 7 |
| Withdrew: Death | 2 | 0 | 2 |
| Withdrew: Withdrawal by subject | 6 | 4 | 4 |
| Withdrew: Alternative therapy | 2 | 0 | 2 |
| Withdrew: Physician decision | 1 | 0 | 1 |
| Withdrew: Error made in lesion measurement | 1 | 0 | 0 |
| Withdrew: Patient had surgery | 1 | 0 | 0 |
| Withdrew: Treatment cycle delay | 0 | 0 | 1 |
| Withdrew: Never started treatment | 1 | 0 | 2 |
Progression-fee survival is defined as the time from randomization to disease progression or death without documentation of progression. Censoring occurred at the date of last disease assessment without progression for cases without documentation of progression, except for cases where death occurred within a short period of time (4 months) following the date last known progression-free, in which case the death was considered an event. Progression is defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
| months | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Progression-free Survival | 5.98 (3.88 to 9.07) | 7.03 (3.91 to 10.32) | 9.20 (5.52 to 11.33) |
Objective response is defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
| proportion of participants | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Proportion of Participants With an Objective Response Rate (CR or PR) | 0.23 (0.13 to 0.35) | 0.44 (0.23 to 0.67) | 0.36 (0.24 to 0.49) |
Adverse events were assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE). Treatment-related adverse events are defined as those that are possibly, probably, or definitely related to protocol therapy.
| proportion of participants | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Proportion of Patients With Grade 3 or Higher Treatment-related Adverse Events | 0.49 (0.38 to 0.59) | 0.81 (0.58 to 0.95) | 0.56 (0.43 to 0.68) |
Overall survival is defined as the time from randomization to death or date last known alive.
| months | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Overall Survival | 19.3 (10.8 to 23.4) | 15.0 (7.06 to 22.3) | 19.2 (12.8 to 25.9) |
Collected over Assessed every 2 weeks while on treatment and for 30 days after the end of treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A (IC) | 55/70 (78.6%) | 33/68 (48.5%) | 64/68 (94.1%) |
| Arm B (ICR) | 15/16 (93.8%) | 13/16 (81.3%) | 16/16 (100%) |
| Arm C (mICR) | 43/50 (86%) | 27/48 (56.3%) | 46/48 (95.8%) |
| Event | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| FatigueGeneral disorders | 1/68 | 5/16 | 5/48 |
| Neutrophil count decreasedInvestigations | 7/68 | 4/16 | 5/48 |
| Abdominal painGastrointestinal disorders | 0/68 | 3/16 | 0/48 |
| DiarrheaGastrointestinal disorders | 8/68 | 3/16 | 7/48 |
| DehydrationMetabolism and nutrition disorders | 1/68 | 3/16 | 2/48 |
| AnemiaBlood and lymphatic system disorders | 2/68 | 2/16 | 3/48 |
| Colonic perforationGastrointestinal disorders | 0/68 | 2/16 | 0/48 |
| Mucositis oralGastrointestinal disorders | 1/68 | 2/16 | 3/48 |
| Anorectal infectionInfections and infestations | 0/68 | 2/16 | 0/48 |
| AnorexiaMetabolism and nutrition disorders | 0/68 | 2/16 | 1/48 |
| Event | Arm A (IC) | Arm B (ICR) | Arm C (mICR) |
|---|---|---|---|
| Rash acneiformSkin and subcutaneous tissue disorders | 48/68 | 14/16 | 30/48 |
| FatigueGeneral disorders | 35/68 | 13/16 | 32/48 |
| AnemiaBlood and lymphatic system disorders | 33/68 | 12/16 | 26/48 |
| DiarrheaGastrointestinal disorders | 36/68 | 12/16 | 30/48 |
| NauseaGastrointestinal disorders | 29/68 | 11/16 | 20/48 |
| White blood cell decreasedInvestigations | 25/68 | 11/16 | 21/48 |
| AlopeciaSkin and subcutaneous tissue disorders | 16/68 | 9/16 | 14/48 |
| Neutrophil count decreasedInvestigations | 10/68 | 9/16 | 17/48 |
| HypomagnesemiaMetabolism and nutrition disorders | 28/68 | 9/16 | 26/48 |
| Platelet count decreasedInvestigations | 17/68 | 8/16 | 20/48 |
Eligible and treated patients are included in this analysis.
| Age, Continuous(years) | Arm A (IC) | Arm B (ICR) | Arm C (mICR) | Total |
|---|---|---|---|---|
| Median | 59.8 (34 to 84) | 60.0 (43 to 76) | 60.4 (37 to 80) | 60.3 (34 to 84) |
| Sex: Female, Male(Participants) | Arm A (IC) | Arm B (ICR) | Arm C (mICR) | Total |
|---|---|---|---|---|
| Female | 25 | 7 | 13 | 45 |
| Male | 37 | 9 | 32 | 78 |
| Ethnicity (NIH/OMB)(Participants) | Arm A (IC) | Arm B (ICR) | Arm C (mICR) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 5 | 2 | 5 | 12 |
| Not Hispanic or Latino | 54 | 13 | 38 | 105 |
| Unknown or Not Reported | 3 | 1 | 2 | 6 |
| Race (NIH/OMB)(Participants) | Arm A (IC) | Arm B (ICR) | Arm C (mICR) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 2 | 0 | 2 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 12 | 1 | 3 | 16 |
| White | 47 | 15 | 37 | 99 |
| More than one race | 1 | 0 | 1 | 2 |
| Unknown or Not Reported | 0 | 0 | 2 | 2 |
Showing the first 100 of 255 sites.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
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Eastern Cooperative Oncology Group