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

This study is ongoing, but not recruiting participants.
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: August 17, 2015
Last verified: August 2015

May 10, 2006
August 17, 2015
September 2006
April 2014   (final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00324415 on ClinicalTrials.gov Archive Site
  • 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
Not Provided
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Anal Cancer
  • 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.
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)
Interventions:
  • Biological: cetuximab
  • Drug: cisplatin
  • Drug: fluorouracil
  • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
April 2016
April 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00324415
AMC-045, U01CA070019, CDR0000440065
No
Not Provided
Not Provided
AIDS Malignancy Consortium
AIDS Malignancy Consortium
  • National Cancer Institute (NCI)
  • The EMMES Corporation
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
AIDS Malignancy Consortium
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP