Clinical trial NCT00324415: Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer
Official title: Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
First posted: 2006-05-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Locoregional Failure Rate at 3 Years
timeFrame: 3 years following completion of therapy
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 1 year
measure: Relapse-free Survival
timeFrame: 1 year
measure: Colostomy-free Survival at 1 Year
timeFrame: 1 year
measure: Overall Survival
timeFrame: 1 year
measure: Quality of Life EORTC Global Score at 1 Year
timeFrame: 1 year
measure: Number of Delayed Toxicities
timeFrame: 90 days following treatment discontinuation
measure: Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment
timeFrame: 1 year following treatment discontinuation
measure: Incidence of Opportunistic Illnesses
timeFrame: 1 year following treatment discontinuation
measure: Objective Response Rate (Complete and Partial)
timeFrame: 3 years following treatment discontinuation
Other outcomes:
measure: Count of Participants by Type of HPV at Baseline
timeFrame: baseline
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical AIDS Research and Education (CARE) Center
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Philadelphia
country: United States
facility: Joan Karnell Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Albert Einstein College of Medicine
name: Joseph A. Sparano, MD
role: STUDY_CHAIR
affiliation: Massachusetts General Hospital
name: Lisa A. Kachnic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
name: David M. Aboulafia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.