Overview

This trial is active, not recruiting.

Condition anal cancer
Treatments cetuximab, cisplatin, fluorouracil, radiation therapy
Phase phase 2
Target EGFR
Sponsor AIDS Malignancy Clinical Trials Consortium
Collaborator National Cancer Institute (NCI)
Start date September 2006
End date April 2014
Trial size 45 participants
Trial identifier NCT00324415, AMC-045, CDR0000440065, U01CA070019

Summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, 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, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin, fluorouracil, and cetuximab together with radiation therapy works in treating patients with HIV and stage I, stage II, or stage III anal cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
All patients will receive combined modality therapy (CMT) with 2 cycles of cisplatin and 5-FU chemotherapy, given concurrently with radiation therapy. CMT consists of: Cetuximab 400 mg/m2 IV Day -7 (1 week before the cycle 1, Day 1 cisplatin/5-FU and RT), then 250 mg/m2 IV Days 1, 8, 15, 22, 29, 36 and 43 (a minimum of 6 and a maximum of 8 doses of cetuximab will be administered, including the loading dose). Cisplatin 75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2) 5-FU 1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
cetuximab Erbitux
400 mg/m2 IV Day -7 (1 week before the cycle 1, Day 1 cisplatin/5-FU and RT), then 250 mg/m2 IV Days 1, 8, 15, 22, 29, 36 and 43 (a minimum of 6 and a maximum of 8 doses of cetuximab will be administered, including the loading dose)
cisplatin Platinol
75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
fluorouracil 5-FU
1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
radiation therapy
Irradiation to tumor site and inguinal nodes beginning on cycle 1, Day 1 cisplatin/5-FU (minimum 45.0 Gy [5 weeks if given on schedule and without interruption], maximum 54.0 Gy [6 weeks if given on schedule and without interruption). IMRT may be used at the discretion of the treating physician.

Primary Outcomes

Measure
Local failure rate at 3 years
time frame: 3 years following treatment discontinuation

Secondary Outcomes

Measure
Progression-free survival
time frame: Up to 5 years following treatment discontinuation
Relapse-free survival
time frame: Up to 5 years after treatment discontinuation
Colostomy-free survival
time frame: Up to 5 years following treatment discontinuation
Overall survival
time frame: Up to 5 years following treatment discontinuation
Quality of life
time frame: 3 years following treatment discontinuation
Toxicity
time frame: 90 days following treatment discontinuation
Changes in viral load and CD4 counts during and for 1 year after completion of study treatment
time frame: 1 year following treatment discontinuation
Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment
time frame: 1 year following treatment discontinuation
Anogenital human papilloma virus (HPV) infection and anal cytology
time frame: 6 months following treatment discontinuation
Objective response rate (complete and partial)
time frame: 3 years following treatment discontinuation

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed stage I-IIIB invasive anal canal or perianal (anal margin) squamous cell carcinoma, including tumors with any of the following nonkeratinizing histologies: - Basaloid - Transitional cell - Cloacogenic - Documented HIV infection by 1 of the following: - Antibody detection - Culture - Quantitative assay of plasma HIV RNA PATIENT CHARACTERISTICS: - Karnofsky performance status 60-100% - Absolute neutrophil count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin ≥ 10 g/dL (transfusions, epoetin alfa, or myeloid growth factor support allowed provided blood counts are stable for ≥ 2 weeks prior to study entry) - Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 60 mL/min - AST and ALT ≤ 3 times ULN - Bilirubin ≤ 2 times ULN - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No acute active, serious, uncontrolled opportunistic infection - No other prior invasive malignancy diagnosed within the past 24 months, excluding in situ cervical cancer, anal dysplasia or carcinoma in situ, nonmelanoma skin carcinoma, or Kaposi's sarcoma that has not required systemic chemotherapy within the past 24 months - No peripheral neuropathy > grade 1 - No severe or poorly controlled diarrhea - No medical or psychiatric illness that would preclude study requirements PRIOR CONCURRENT THERAPY: - No prior chemotherapy or radiotherapy for this malignancy - Prior radiotherapy for another condition (e.g., Kaposi's sarcoma) allowed

Additional Information

Official title Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma
Principal investigator Lisa A. Kachnic, MD
Description OBJECTIVES: Primary - Determine the 2-year local failure rate in patients with HIV-associated stage I-IIIB anal carcinoma treated with cisplatin, fluorouracil, cetuximab, and radiotherapy. - Determine the objective response rate (complete and partial), progression-free survival, relapse-free survival, colostomy-free survival, overall survival, quality of life, and overall toxicity in patients treated with this regimen. Secondary - Characterize the effect of this regimen on the underlying HIV condition by describing changes in viral load, CD4 counts, and the incidence of opportunistic illnesses, including the development of AIDS during and in the first year after treatment. - Evaluate the effect of this regimen on anogenital human papilloma virus (HPV) infection and anal cytology. OUTLINE: This is an open-label, multicenter study. Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 35*, fluorouracil IV continuously on days 1-4 and 29-32, and cisplatin IV over 1 hour on days 1 and 29. Beginning on day 1, patients undergo concurrent radiotherapy to the primary tumor 5 days a week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. NOTE: *Patients receiving 7 weeks of radiotherapy also receive cetuximab on days 42 and 49. Quality of life is assessed at baseline, at the completion of study treatment, and then at months 3, 6, 12, 24, and 36. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in August 2014.
Information provided to ClinicalTrials.gov by AIDS Malignancy Clinical Trials Consortium.