Anal CancerPhase 2NCT00324415
Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer
A Phase 2 study testing cetuximab, cisplatin and fluorouracil in people with Anal Cancer, run by AIDS Malignancy Consortium at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Anal Cancer
- What is being tested?
- cetuximab, cisplatin and fluorouracil
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2006to May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093-0658
UCLA Clinical AIDS Research and Education (CARE) Center
Los Angeles, California, 90095-1793
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, 19106
Benaroya Research Institute at Virginia Mason Medical Center
Seattle, Washington, 98101
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: 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.
Read the 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.
- Conditions
- Anal Cancer
- Being tested
- cetuximab, cisplatin, fluorouracil, radiation therapy
- 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
- Medical subject headings
- Anus Neoplasms, Anal Canal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Also called Erbitux
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)
cisplatinDrug
Also called Platinol
75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2)
fluorouracilDrug
Also called 5-FU, Adrucil, Carac, Efudex
1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2)
radiation therapyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| CMT with Radiation Therapy | Experimental | 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) Receives: Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Locoregional 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
Measured: 3 years following completion of therapy
Secondary outcomes (9)
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.
Measured: 1 year
Relapse-free Survival
Percentage of participants who are alive and have not experienced progressive disease and have not relapsed
Measured: 1 year
Colostomy-free Survival at 1 Year
Percentage of participants who are alive and have not had a colostomy
Measured: 1 year
Overall Survival
Percentage of participants who are alive at one year
Measured: 1 year
Quality of Life EORTC Global Score at 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
Measured: 1 year
Number of Delayed Toxicities
Delayed toxicities are defined as toxicities that occur over 90 days following treatment completion
Measured: 90 days following treatment discontinuation
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
Measured: 1 year following treatment discontinuation
Incidence of Opportunistic Illnesses
Incidence of opportunistic illnesses, including the development of AIDS during and for 1 year after completion of study treatment
Measured: 1 year following treatment discontinuation
Objective Response Rate (Complete and Partial)
Number of participants with complete and partial responses based on the RECIST criteria
Measured: 3 years following treatment discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2006 (estimated)
- Study startSep 2006
- Primary completionApr 2014
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIDS Malignancy Consortium
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC
- Responsible party
- Sponsor
- Investigators
- Joseph A. Sparano, MD, Study chair, Albert Einstein College of MedicineLisa A. Kachnic, MD, Principal investigator, Massachusetts General HospitalDavid M. Aboulafia, MD, Principal investigator, Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00324415
- Sponsor's protocol ID
- AMC-045
- Other IDs
- U01CA070019, CDR0000440065
- Status last verified
- May 2025
- First submitted
- 10 May 2006
- Last updated
- 30 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 27937092
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Combined Modality Therapy Plus Cetuximab in HIV-Associated Anal Carcinoma
- ClinicalTrials.gov ID
- NCT00324415
- Acronym / sponsor ID
- AMC-045
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- AIDS Malignancy ConsortiumResearch network
- Collaborators
- National Cancer Institute (NCI), The Emmes Company, LLC
- Study start
- Sep 2006
- Primary completion
- Apr 2014 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 11 May 2006 (estimated)
- Results
- Posted 17 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CMT with Radiation Therapy | Experimental | Biological: cetuximab, Drug: cisplatin, Drug: fluorouracil, Radiation: radiation therapyAll 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) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximabAlso: Erbitux400 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) | Biological | CMT with Radiation Therapy |
| cisplatinAlso: Platinol75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2) | Drug | CMT with Radiation Therapy |
| fluorouracilAlso: 5-FU, Adrucil, Carac, Efudex1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2) | Drug | CMT with Radiation Therapy |
| radiation therapyIrradiation 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. | Radiation | CMT with Radiation Therapy |
Primary outcome
Locoregional Failure Rate at 3 Years
Time frame: 3 years following completion of therapy
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
9 secondary outcomes
Progression-free Survival
Time frame: 1 year
Relapse-free Survival
Time frame: 1 year
Colostomy-free Survival at 1 Year
Time frame: 1 year
Overall Survival
Time frame: 1 year
Quality of Life EORTC Global Score at 1 Year
Time frame: 1 year
Number of Delayed Toxicities
Time frame: 90 days following treatment discontinuation
Changes in CD4 Counts During and for 1 Year After Completion of Study Treatment
Time frame: 1 year following treatment discontinuation
Incidence of Opportunistic Illnesses
Time frame: 1 year following treatment discontinuation
Objective Response Rate (Complete and Partial)
Time frame: 3 years following treatment discontinuation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27937092Sparano 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.
Related trials for Anal Cancer
Active, not recruitingPhase 3
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 3
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 2
Intratreatment FDG-PET During Radiation Therapy for Gynecologic and Gastrointestinal Cancers
Cancer of the Cervix, Vulvar Cancer
Active, not recruitingObservational study
Anal Cancer Radiotherapy Study
Anal Cancer
Active, not recruitingPhase 1
A Study of Safety and Efficacy of KFA115 Alone and in Combo With Pembrolizumab in Patients With Select Advanced Cancers
Carcinoma, Non-Small-Cell Lung, Cutaneous Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab, cisplatin and fluorouracil in people with Anal Cancer, run by AIDS Malignancy Consortium at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Locoregional Failure Rate at 3 Years (time frame: 3 years following completion of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00324415, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2025; AzTrials last refreshed its copy on 26 Oct 2026.