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

Primary Purpose

Anal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cetuximab
cisplatin
fluorouracil
radiation therapy
Sponsored by
AIDS Malignancy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anal Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rebecca and John Moores UCSD Cancer Center
  • UCLA Clinical AIDS Research and Education (CARE) Center
  • Beth Israel Deaconess Medical Center
  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Albert Einstein Cancer Center at Albert Einstein College of Medicine
  • Joan Karnell Cancer Center at Pennsylvania Hospital
  • Benaroya Research Institute at Virginia Mason Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CMT with Radiation Therapy

Arm Description

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)

Outcomes

Primary Outcome Measures

Local Failure Rate at 3 Years
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
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
Percentage of participants who are alive and have not experienced progressive disease and have not relapsed
Colostomy-free Survival at 1 Year
Percentage of participants who are alive and have not had a colostomy
Overall Survival
Percentage of participants who are alive at one year
Quality of Life
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
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
Change in absolute CD4 counts from start of treatment to 1 year after completion of study treatment
Incidence of Opportunistic Illnesses
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
Objective Response Rate (Complete and Partial)
Number of participants with complete and partial responses based on the RECIST criteria

Full Information

First Posted
May 10, 2006
Last Updated
May 3, 2018
Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00324415
Brief Title
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

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Malignancy Consortium
Collaborators
National Cancer Institute (NCI), The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CMT with Radiation Therapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
Platinol
Intervention Description
75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-FU, Adrucil, Carac, Efudex, Fluoroplex
Intervention Description
1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Local Failure Rate at 3 Years
Description
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
Time Frame
3 years following treatment discontinuation
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
Time Frame
1 year
Title
Relapse-free Survival
Description
Percentage of participants who are alive and have not experienced progressive disease and have not relapsed
Time Frame
1 year
Title
Colostomy-free Survival at 1 Year
Description
Percentage of participants who are alive and have not had a colostomy
Time Frame
1 year
Title
Overall Survival
Description
Percentage of participants who are alive at one year
Time Frame
1 year
Title
Quality of Life
Description
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
Time Frame
1 year
Title
Toxicity
Description
Delayed toxicities are defined as toxicities that occur over 90 days following treatment completion
Time Frame
90 days following treatment discontinuation
Title
Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment
Description
Change in absolute CD4 counts from start of treatment to 1 year after completion of study treatment
Time Frame
1 year following treatment discontinuation
Title
Incidence of Opportunistic Illnesses
Description
Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment
Time Frame
1 year following treatment discontinuation
Title
Anogenital Human Papilloma Virus (HPV) Infection and Anal Cytology
Time Frame
6 months following treatment discontinuation
Title
Objective Response Rate (Complete and Partial)
Description
Number of participants with complete and partial responses based on the RECIST criteria
Time Frame
3 years following treatment discontinuation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph A. Sparano, MD
Organizational Affiliation
Albert Einstein College of Medicine
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Lisa A. Kachnic, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David M. Aboulafia, MD
Organizational Affiliation
Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rebecca and John Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0658
Country
United States
Facility Name
UCLA Clinical AIDS Research and Education (CARE) Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1793
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Albert Einstein Cancer Center at Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Joan Karnell Cancer Center at Pennsylvania Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19106
Country
United States
Facility Name
Benaroya Research Institute at Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27937092
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.
Results Reference
result

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

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