Monoclonal Antibody Plus Chemotherapy in Treating Patients With Advanced Colorectal Cancer That Overexpresses HER2

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: irinotecan hydrochloride

Biological: trastuzumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00003995

CDR0000067205 (Registry Identifier)

NCI-2012-02307

NCI-T98-0078

PCI-98-056

Details and patient eligibility

About

Phase II trial to study the effectiveness of the monoclonal antibody trastuzumab and chemotherapy with irinotecan in treating patients who have stage IV colorectal cancer that overexpresses HER2. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.

Full description

OBJECTIVES:

I. Determine the objective response rate of irinotecan and trastuzumab in patients with stage IV colorectal cancer and p185 HER2 overexpression.

II. Evaluate the safety and toxic effects of this treatment regimen in these patients.

III. Determine the overall survival and time to progression in these patients in response to this treatment regimen.

IV. Determine the pharmacokinetics of trastuzumab in combination with irinotecan and antibodies to trastuzumab in these patients.

V. Determine the expression of HER2/neu in these patients.

OUTLINE: This is a multicenter study.

Patients receive a loading dose of trastuzumab IV over 90 minutes on week 1, and over 30-90 minutes weekly thereafter. Patients receive irinotecan IV over 90 minutes following trastuzumab weekly for 4 weeks. Courses are repeated every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

Enrollment

32 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV colorectal cancer with p185 HER2 overexpression
Bidimensionally measurable disease Indicator lesion must be outside of irradiated field No symptomatic CNS brain metastases

PATIENT CHARACTERISTICS:

Performance status: ECOG 0-2
Absolute granulocyte count at least 1,500/mm3
Platelet count at least 100,000/mm3
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
SGOT no greater than 3.0 times ULN
Creatinine no greater than 2.0 mg/dL
LVEF at least 45% by MUGA or ECHO
No myocardial infarction within the past 6 months
No congestive heart failure
No unstable angina
No clinically significant pericardial effusion or arrhythmia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after study
No other prior malignancy within the past 5 years, except:
- Curatively treated basal or squamous cell skin cancer
- Curatively treated carcinoma in situ of the cervix
- No active serious infection or serious underlying medical condition that would prevent compliance
- No dementia or significantly altered mental status

PRIOR CONCURRENT THERAPY:

Concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa allowed
No prior trastuzumab
No more than 1 prior chemotherapy regimen for advanced disease (if progressed during or within 6 months of adjuvant therapy considered to have had 1 regimen for advanced disease)
No prior irinotecan
Concurrent contraception, estrogen replacement therapy, or megestrol acetate for anorexia allowed
Greater than 3 weeks since prior radiotherapy and recovered
Greater than 3 weeks since major surgery (except simple biopsy or venous access placement) and recovered
At least 3 weeks since prior investigational nonneoplastic drugs