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

Overview

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.

Full Title of Study: “Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2014

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.

Interventions

  • 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)
  • Drug: cisplatin
    • 75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
  • Drug: fluorouracil
    • 1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
  • 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.

Arms, Groups and Cohorts

  • 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)

Clinical Trial Outcome Measures

Primary Measures

  • Local Failure Rate at 3 Years
    • Time Frame: 3 years following treatment discontinuation
    • 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 Measures

  • Progression-free Survival
    • Time Frame: 1 year
    • 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
    • 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
    • Percentage of participants who are alive and have not had a colostomy
  • Overall Survival
    • Time Frame: 1 year
    • Percentage of participants who are alive at one year
  • Quality of Life
    • Time Frame: 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
  • Toxicity
    • Time Frame: 90 days following treatment discontinuation
    • 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
    • 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
    • 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
  • Objective Response Rate (Complete and Partial)
    • Time Frame: 3 years following treatment discontinuation
    • Number of participants with complete and partial responses based on the RECIST criteria

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 120 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • AIDS Malignancy Consortium
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Joseph A. Sparano, MD, Study Chair, Albert Einstein College of Medicine
    • Lisa A. Kachnic, MD, Principal Investigator, Massachusetts General Hospital
    • David M. Aboulafia, MD, Principal Investigator, Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center

Citations Reporting on Results

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.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.