Combination Chemotherapy Plus Trastuzumab in Treating Patients With Advanced, Recurrent, or Metastatic Colorectal Cancer - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00006015

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying combination chemotherapy plus trastuzumab to see how well it works in treating patients with advanced, recurrent, or metastatic colorectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Biological: trastuzumab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study Evaluating the Combination of 5-Fluorouracil, Leucovorin, Oxaliplatin, and Herceptin in the Treatment of Patients With Metastatic Colorectal Cancer Who Have Progressed After 5-FU and/or Irinotecan-Containing Therapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Trastuzumab Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:

Response rate [ Time Frame: Every 2 tx cycles ] [ Designated as safety issue: No ]
Time to progression [ Time Frame: Every 2 tx cycles ] [ Designated as safety issue: No ]
Overall toxicity [ Time Frame: Each cycle during tx ] [ Designated as safety issue: Yes ]

Enrollment:	26
Study Start Date:	May 2000
Primary Completion Date:	December 2002 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Combination Chemotx Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy	Biological: trastuzumab 4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22) Other Name: Herceptin Drug: fluorouracil 500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break Other Name: 5-FU Drug: leucovorin calcium 500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break Drug: oxaliplatin 85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle

Arms

Assigned Interventions

Experimental: Combination Chemotx

Combination chemotherapy for metastatic colorectal cancer in patients who have disease progression after 5-FU and/or irinotecan-containing therapy

Biological: trastuzumab

4 mg/kg IV infusion Day 1, then weekly 2 mg/kg IV infusion (on Days 8, 15, & 22)

Other Name: Herceptin

Drug: fluorouracil

500 mg/sq m IV push weekly for 3 weeks, followed by a 1 wk break

Other Name: 5-FU

Drug: leucovorin calcium

500 mg/sq m IV infusion over 2 hours weekly for 3 weeks, then a 1 wk break

Drug: oxaliplatin

85 mg/sq m IV infusion over 2 hours Days 1 & 15 of each cycle

Detailed Description:

OBJECTIVES:

Determine the response rate of patients who overexpress HER-2/neu with metastatic colorectal adenocarcinoma who have progressed on at least 1 prior, but no more than 2 prior, chemotherapy regimens for metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, oxaliplatin, and trastuzumab (Herceptin).
Determine the time to progression of these patients treated with this regimen.
Determine the overall toxicity of this regimen in these patients.

OUTLINE: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, 15, and 22, followed by oxaliplatin IV over 2 hours on days 1 and 15, and then followed by leucovorin calcium IV over 2 hours on days 1, 8, and 15. Fluorouracil IV is administered at the midpoint of the leucovorin calcium infusion on days 1, 8, and 15. Treatment continues every 28 days in the absence of unacceptable toxicity or disease progression.

PROJECTED ACCRUAL: A total of 20-45 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed advanced, recurrent, or metastatic colorectal adenocarcinoma
Resected CNS metastases stable greater than 1 month after completion of radiotherapy for CNS metastases eligible
- No existing CNS metastases allowed
Measurable disease
- At least 1 dimension as at least 20 mm with conventional techniques OR
- At least 10 mm with spiral CT scan
- No truly nonmeasurable lesions:
  - Bone lesions
  - Leptomeningeal disease
  - Lymphangitis cutis/pulmonis
  - Abdominal masses not confirmed and followed by imaging techniques
  - Cystic lesions
Must have progressed on at least 1 prior, but no more than 2 prior, fluorouracil and/or irinotecan containing treatment regimens for metastatic colorectal cancer
Must have documented HER-2/neu overexpression by immunohistochemistry staining
- Staining score at least 2+

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Granulocyte count at least 1,500/mm3
Platelet count at least 100,000/mm3

Hepatic:

Bilirubin no greater than 2.0 mg/dL
AST no greater than 2.5 times upper limit of normal

Renal:

Creatinine normal OR
Creatinine clearance at least 60 mL/min

Cardiovascular:

No history of cardiac ischemia or congestive heart failure
LVEF at least 50% by ECG or MUGA

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
No concurrent second malignancy except nonmelanoma skin cancers or carcinoma in situ of the cervix unless completed therapy and considered to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

See Disease Characteristics
No prior platinum containing chemotherapy
At least 3 weeks since prior chemotherapy and recovered
No other concurrent chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

At least 3 weeks since prior radiotherapy and recovered

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006015

Show 47 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeffrey W. Clark, MD

Massachusetts General Hospital

More Information

Publications:

Clark JW, Niedzwiecki D, Hollis D, et al.: Phase II trial of 5-fluororuacil (5-FU), leucovorin (LV), oxaliplatin (Ox), and trastuzamab (T) for patients with metastatic colorectal cancer (CRC) refractory to initial therapy. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-3584, 2003.

Responsible Party:	Monica M Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:	NCT00006015 History of Changes
Other Study ID Numbers:	CDR0000068024, U10CA031946, CALGB-89902
Study First Received:	July 5, 2000
Last Updated:	June 21, 2011
Health Authority:	United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:

stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer

recurrent rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:

Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Trastuzumab
Leucovorin

Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on February 09, 2012