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

NCT00324415 | Completed Phase 2 Results

• 3 other identifiers: AMC-045U01CA070019CDR0000440065
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

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.

Conditions

Anal Cancer

Keywords

stage I anal cancer; stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; squamous cell carcinoma of the anus; basaloid carcinoma of the anus; cloacogenic carcinoma of the anus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Progression-free Survival

  1 year

• Relapse-free Survival

  1 year

• Colostomy-free Survival at 1 Year

  1 year

• Overall Survival

  1 year

• Quality of Life EORTC Global Score at 1 Year

  1 year

Other Outcomes (1)

• Count of Participants by Type of HPV at Baseline

  baseline

Study Arms (1)

CMT with Radiation Therapy

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)

Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiation therapy

Interventions

cetuximab 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)

Also known as: Erbitux

CMT with Radiation Therapy

cisplatin DRUG

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

Also known as: Platinol

CMT with Radiation Therapy

fluorouracil DRUG

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

Also known as: 5-FU, Adrucil, Carac, Efudex, Fluoroplex

CMT with Radiation Therapy

radiation therapy 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.

CMT with Radiation Therapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• AIDS Malignancy Consortium: lead
• National Cancer Institute (NCI): collaborator
• The Emmes Company, LLC: collaborator

Study Sites (7)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

UCLA Clinical AIDS Research and Education (CARE) Center

Los Angeles, California, 90095-1793, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Joan Karnell Cancer Center at Pennsylvania Hospital

Philadelphia, Pennsylvania, 19106, United States

Location

Benaroya Research Institute at Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• 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.

  PMID: 27937092 RESULT

MeSH Terms

Conditions

Anus Neoplasms; Anal Canal Carcinoma

Interventions

Cetuximab; Cisplatin; Fluorouracil; Radiotherapy

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Director, AMC Statistical Center
• Organization: AMC

jylee@uams.edu

501-526-6712

Study Officials

• Joseph A. Sparano, MD

  Albert Einstein College of Medicine

  STUDY CHAIR

• Lisa A. Kachnic, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• David M. Aboulafia, MD

  Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2006
• First Posted: May 11, 2006
• Study Start: September 1, 2006
• Primary Completion: April 1, 2014
• Study Completion: May 1, 2016
• Last Updated: May 30, 2025
• Results First Posted: September 17, 2015

Record last verified: 2025-05

Locations

US (7)