Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer
|ClinicalTrials.gov Identifier: NCT00324415|
Recruitment Status : Completed
First Posted : May 11, 2006
Results First Posted : September 17, 2015
Last Update Posted : March 6, 2018
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 or disease||Intervention/treatment||Phase|
|Anal Cancer||Biological: cetuximab Drug: cisplatin Drug: fluorouracil Radiation: radiation therapy||Phase 2|
- 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.
- 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 (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma|
|Study Start Date :||September 2006|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||May 2016|
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:
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: ErbituxDrug: cisplatin
75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
Other Name: PlatinolDrug: fluorouracil
1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
Other Names: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.
- 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
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00324415
|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|
|Study Chair:||Joseph A. Sparano, MD||Albert Einstein College of Medicine, Inc.|
|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|