test

Irinotecan Hydrochloride and Cetuximab With or Without Ramucirumab in Treating Patients With Advanced Colorectal Cancer With Progressive Disease After Treatment With Bevacizumab-Containing Chemotherapy

Conditions

Colorectal Cancer

Trial Phase

Phase 2

Trial Purpose and Description

Trial Purpose


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.

Trial Description


OBJECTIVES:

- To evaluate the progression-free survival of patients with advanced K-ras wild-type
colorectal cancer, following progression on bevacizumab-contained chemotherapy, treated
with irinotecan hydrochloride and cetuximab with versus without ramucirumab as
second-line therapy.

- To evaluate the response rate in patients treated with these regimens.

- To evaluate the grade 3-4 toxicity rates of these regimens in these patients.

- To evaluate the overall suvival of patients treated with these regimens.

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.

- Arm I: Patients receive cetuximab IV over 60-120 minutes and irinotecan hydrochloride
over 60-90 minutes on day 1.

- Arm II: Patients receive ramucirumab IV over 60 minutes on day 1 and cetuximab and
irinotecan hydrochloride as in arm I.

In both 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.

Participation Guidelines

Age:
18 Years - N/A
Gender:
Both

Eligibility Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the colon or rectum, including:

- Advanced disease

- Histologic variants of adenocarcinoma allowed

- K-ras wild type based on either primary or metastatic tumor

- No mutated type

- Measurable disease

- Must have received prior first-line therapy comprising oxaliplatin-based
fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal
cancer

- No more than 42 days since confirmed disease progression

- No brain or CNS metastases

PATIENT CHARACTERISTICS:

- Performance status 0-1

- ANC = 1,500/µL

- Platelet count = 75,000/µL

- Hemoglobin = 9 g/dL

- Serum creatinine = 1.5 times upper limit of normal (ULN) OR creatinine clearance = 40
mL/min

- Urine protein = 1+ on dipstick or routine urinalysis (if = 2+, a 24-hour urine
collection must demonstrate < 1,000 mg of protein)

- Total bilirubin = 2.0 mg/dL

- AST and ALT = 3.0 times ULN (5.0 times ULN for patients with liver metastases)

- INR = 1.6 (= 3.0 for patients on warfarin and no active bleeding [i.e., no bleeding
within the past 14 days])

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- No clinically significant (equivalent to NCI CTCAE grade 3-4) bleeding episodes
within the past 3 months

- None of the following:

- Active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Symptomatic or poorly controlled cardiac arrhythmia

- Uncontrolled thrombotic or hemorrhagic disorder

- No uncontrolled or poorly controlled hypertension despite standard medical management
(e.g., consistently systolic BP > 160 mm Hg and diastolic BP > 90 mm Hg)

- No acute arterial thrombotic events within the past 6 months, including
cerebrovascular accident, transient ischemic attack, myocardial infarction, or
unstable angina

- No other cancer requiring therapy within the past 3 years except in situ carcinoma or
nonmelanoma skin cancer

- No acute or subacute intestinal obstruction

- No history of inflammatory bowel disease requiring pharmacological and/or surgical
intervention within the past 12 months

- No known allergy to any of the treatment components

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 28 days and no more than 90 days since prior bevacizumab

- No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus
bevacizumab for colorectal cancer

- No major surgery within the past 28 days

- No subcutaneous venous access device placement within the past 7 days

- Concurrent stable dose of oral anticoagulant or low-molecular weight heparin allowed
Sponsor:
National Cancer Institute (NCI)
Pam Cogliano
Dates:
November 2010
Last Updated:
September 19, 2014
Study HIC#:

Clinicaltrials.gov ID: NCT01079780