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

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
The EMMES Corporation
Information provided by (Responsible Party):
AIDS Malignancy Consortium
ClinicalTrials.gov Identifier:
NCT00324415
First received: May 10, 2006
Last updated: June 14, 2016
Last verified: June 2016
  Purpose

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.


Condition Intervention Phase
Anal Cancer
Biological: cetuximab
Drug: cisplatin
Drug: fluorouracil
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Consortium:

Primary Outcome Measures:
  • Local Failure Rate at 3 Years [ Time Frame: 3 years following treatment discontinuation ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.

  • Relapse-free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of participants who are alive and have not experienced progressive disease and have not relapsed

  • Colostomy-free Survival at 1 Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of participants who are alive and have not had a colostomy

  • Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of participants who are alive at one year

  • Quality of Life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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

  • Toxicity [ Time Frame: 90 days following treatment discontinuation ] [ Designated as safety issue: Yes ]
    Delayed toxicities are defined as toxicities that occur over 90 days following treatment completion

  • Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment [ Time Frame: 1 year following treatment discontinuation ] [ Designated as safety issue: No ]
    Change in absolute CD4 counts from start of treatment to 1 year after completion of study treatment

  • Incidence of Opportunistic Illnesses [ Time Frame: 1 year following treatment discontinuation ] [ Designated as safety issue: No ]
    Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment

  • Anogenital Human Papilloma Virus (HPV) Infection and Anal Cytology [ Time Frame: 6 months following treatment discontinuation ] [ Designated as safety issue: No ]
  • Objective Response Rate (Complete and Partial) [ Time Frame: 3 years following treatment discontinuation ] [ Designated as safety issue: No ]
    Number of participants with complete and partial responses based on the RECIST criteria


Enrollment: 45
Study Start Date: September 2006
Study Completion Date: May 2016
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Erbitux
Drug: cisplatin
75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
Other Name: 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
  • Adrucil
  • Carac
  • 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324415

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, United States, 90095-1793
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
United States, Pennsylvania
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19106
United States, Washington
Benaroya Research Institute at Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Sponsors and Collaborators
AIDS Malignancy Consortium
National Cancer Institute (NCI)
The EMMES Corporation
Investigators
Study Chair: Joseph A. Sparano, MD Albert Einstein College of Medicine of Yeshiva University
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
  More Information

Responsible Party: AIDS Malignancy Consortium
ClinicalTrials.gov Identifier: NCT00324415     History of Changes
Other Study ID Numbers: AMC-045  U01CA070019  CDR0000440065 
Study First Received: May 10, 2006
Results First Received: July 22, 2015
Last Updated: June 14, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
United States: Federal Government

Keywords provided by AIDS Malignancy Consortium:
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

Additional relevant MeSH terms:
Anus Neoplasms
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
Cisplatin
Cetuximab
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 08, 2016