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

Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Anal Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Los Angeles, California, United States, 90095-1793
      • UCLA Clinical AIDS Research and Education (CARE) Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Joan Karnell Cancer Center at Pennsylvania Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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)

Biological: 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); Other Names: Erbitux; Drug: cisplatin; 75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2); Other Names: Platinol; Drug: fluorouracil; 1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2); Other Names: 5-FU; Carac; Adrucil; Efudex; Fluoroplex; Radiation: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional Failure Rate at 3 Years	Patients will be classified into two groups for purposes of primary endpoint analysis: failure or no failure at 3 years (in the primary analysis, patients lost to follow-up prior to 3 years will be considered failures). For the secondary endpoint of objective response, patients will be classified as responders	3 years following completion of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival at 1 year is the percentage of patients who are alive and have not experienced progressive disease, defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, or the appearance of one or more new lesions.	1 year
Relapse-free Survival	Percentage of participants who are alive and have not experienced progressive disease and have not relapsed	1 year
Colostomy-free Survival at 1 Year	Percentage of participants who are alive and have not had a colostomy	1 year
Overall Survival	Percentage of participants who are alive at one year	1 year
Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment	Change in absolute CD4 counts from start of treatment to 1 year after completion of study treatment	1 year following treatment discontinuation
Incidence of Opportunistic Illnesses	Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment	1 year following treatment discontinuation
Objective Response Rate (Complete and Partial)	Number of participants with complete and partial responses based on the RECIST criteria	3 years following treatment discontinuation
Quality of Life EORTC Global Score at 1 Year	EORTC QLQ-C30 Global Score at 1 year. The EORTC QLQ-C30 is a validated questionnaire that evaluates quality of life. The global score is an overall score for quality of life that ranges from 0 to 100. Higher scores indicate between quality of life	1 year
Number of Delayed Toxicities	Delayed toxicities are defined as toxicities that occur over 90 days following treatment completion	90 days following treatment discontinuation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of Participants by Type of HPV at Baseline	Descriptive statistics will be used to describe the types of HPV found in baseline anal swabs and tissue biopsies. Proportion of cases with each type will be summarized	baseline

Collaborators and Investigators

• Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); The Emmes Company, LLC
• Investigators: Principal Investigator: Lisa A. Kachnic, MD, Massachusetts General Hospital; Principal Investigator: David M. Aboulafia, MD, Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center; Study Chair: Joseph A. Sparano, MD, Albert Einstein College of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 10, 2006
• First Submitted That Met QC Criteria: May 10, 2006
• First Posted (Estimated): May 11, 2006

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; squamous cell carcinoma of the anus; stage I anal cancer; cloacogenic carcinoma of the anus; basaloid carcinoma of the anus
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Anus Diseases; Rectal Neoplasms; Anus Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Cetuximab; Fluorouracil
• Other Study ID Numbers: AMC-045; U01CA070019 (U.S. NIH Grant/Contract); CDR0000440065 (Other Identifier: NCI)