Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer

NCT ID: NCT00324415

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2016-05-31

Brief 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.

Detailed 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.

Conditions

Anal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CMT with Radiation Therapy

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)

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)

fluorouracil

Intervention Type: DRUG

1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)

radiation therapy

Intervention Type: RADIATION

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.

Interventions

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)

Intervention Type: BIOLOGICAL

cisplatin

75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)

Intervention Type: DRUG

fluorouracil

1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

Erbitux; Platinol; 5-FU; Adrucil; Carac; Efudex; Fluoroplex

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

AIDS Malignancy Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph A. Sparano, MD

Role: STUDY_CHAIR

Albert Einstein College of Medicine

Lisa A. Kachnic, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

David M. Aboulafia, MD

Role: PRINCIPAL_INVESTIGATOR

Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center

Locations

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, United States

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Benaroya Research Institute at Virginia Mason Medical Center

Seattle, Washington, United States

Countries

United States

References

Sparano JA, Lee JY, Palefsky J, Henry DH, Wachsman W, Rajdev L, Aboulafia D, Ratner L, Fitzgerald TJ, Kachnic L, Mitsuyasu R. Cetuximab Plus Chemoradiotherapy for HIV-Associated Anal Carcinoma: A Phase II AIDS Malignancy Consortium Trial. J Clin Oncol. 2017 Mar;35(7):727-733. doi: 10.1200/JCO.2016.69.1642. Epub 2016 Dec 12.

Reference Type: RESULT

PMID: 27937092 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

U01CA070019

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000440065

Identifier Type: OTHER

Identifier Source: secondary_id

AMC-045

Identifier Type: -

Identifier Source: org_study_id