Ignite Creation Date:
2025-12-24 @ 10:56 PM
Ignite Modification Date:
2025-12-25 @ 8:24 PM
Study NCT ID:
NCT02314169
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-04-29
First Post:
2014-12-10
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Nivolumab With or Without Ipilimumab in Treating Patients With Refractory Metastatic Anal Canal Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Multi-Institutional Phase 2 Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Refractory Metastatic Squamous Cell Carcinoma of the Anal Canal
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with anal canal cancer that has not responded to previous treatment (refractory) and that has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate overall response rate (ORR) with nivolumab in patients with previously treated metastatic squamous cell carcinoma (SCCA) of the anal canal. (Part A) II. To determine an improvement in progression-free survival (PFS) when nivolumab is combined with ipilimumab versus (vs.) nivolumab alone in patients with previously treated metastatic SCCA (Part B).
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) of nivolumab in patients with previously treated metastatic SCCA of the anal canal. (Part A) II. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of the anal canal treated with nivolumab. (Part A) III. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated metastatic SCCA of the anal canal when treated with nivolumab. (Part A) IV. To evaluate the overall response rate (ORR) of nivolumab plus or minus ipilimumab in patients with previously treated metastatic SCCA of the anal canal. (Part B) V. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of the anal canal treated with nivolumab plus or minus ipilimumab. (Part B) VI. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated metastatic SCCA of the anal canal when treated with nivolumab plus or minus ipilimumab. (Part B)
EXPLORATORY OBJECTIVES:
I. To evaluate ORR, PFS, and OS based on expression of programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 (PD-1), peritumoral cluster of differentiation (CD)8+ tumor infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal when treated with nivolumab. (Part A) II. To evaluate radiographic responses according to relative changes in proportions of anti-human papillomavirus (HPV) specific CD8+ and CD4+ TILs and regulatory T cells in patients with previously treated metastatic SCCA of the anal canal following treatment with nivolumab, analyzed from serial peripheral blood samples. (Part A) III. To evaluate ORR, PFS, and OS based on expression of PD-L1, PD-1, peritumoral CD8+ tumor infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal when treated with nivolumab plus or minus ipilimumab. (Part B) IV. To evaluate radiographic responses according to relative changes in proportions of anti-HPV specific CD8+ and CD4+ TILs and regulatory T cells in patients with previously treated metastatic SCCA of the anal canal following treatment with nivolumab plus or minus ipilimumab. (Part B)
OUTLINE:
PART A: Patients receive nivolumab intravenously (IV) over 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.
PART B: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab IV over 30 minutes once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
ARM II: Patients receive nivolumab as in Arm I. Patients also receive ipilimumab IV over 30 minutes once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
After completion of study treatment, patients are followed up for 100 days and then every 3 months for 2 years.
I. To evaluate overall response rate (ORR) with nivolumab in patients with previously treated metastatic squamous cell carcinoma (SCCA) of the anal canal. (Part A) II. To determine an improvement in progression-free survival (PFS) when nivolumab is combined with ipilimumab versus (vs.) nivolumab alone in patients with previously treated metastatic SCCA (Part B).
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) of nivolumab in patients with previously treated metastatic SCCA of the anal canal. (Part A) II. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of the anal canal treated with nivolumab. (Part A) III. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated metastatic SCCA of the anal canal when treated with nivolumab. (Part A) IV. To evaluate the overall response rate (ORR) of nivolumab plus or minus ipilimumab in patients with previously treated metastatic SCCA of the anal canal. (Part B) V. To evaluate overall survival (OS) in patients with previously treated metastatic SCCA of the anal canal treated with nivolumab plus or minus ipilimumab. (Part B) VI. To evaluate the grade 3 and 4 toxicity rate in patients with previously treated metastatic SCCA of the anal canal when treated with nivolumab plus or minus ipilimumab. (Part B)
EXPLORATORY OBJECTIVES:
I. To evaluate ORR, PFS, and OS based on expression of programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 (PD-1), peritumoral cluster of differentiation (CD)8+ tumor infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal when treated with nivolumab. (Part A) II. To evaluate radiographic responses according to relative changes in proportions of anti-human papillomavirus (HPV) specific CD8+ and CD4+ TILs and regulatory T cells in patients with previously treated metastatic SCCA of the anal canal following treatment with nivolumab, analyzed from serial peripheral blood samples. (Part A) III. To evaluate ORR, PFS, and OS based on expression of PD-L1, PD-1, peritumoral CD8+ tumor infiltrating lymphocytes (TILs), peritumoral CD4+ TILs, and regulatory T cells as analyzed from tumor biopsies in previously treated patients with metastatic SCCA of the anal canal when treated with nivolumab plus or minus ipilimumab. (Part B) IV. To evaluate radiographic responses according to relative changes in proportions of anti-HPV specific CD8+ and CD4+ TILs and regulatory T cells in patients with previously treated metastatic SCCA of the anal canal following treatment with nivolumab plus or minus ipilimumab. (Part B)
OUTLINE:
PART A: Patients receive nivolumab intravenously (IV) over 60 minutes once every two weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.
PART B: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive nivolumab IV over 30 minutes once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
ARM II: Patients receive nivolumab as in Arm I. Patients also receive ipilimumab IV over 30 minutes once every 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood sample collection throughout the study.
After completion of study treatment, patients are followed up for 100 days and then every 3 months for 2 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2014-02420 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| NCI9673 | None | None | View | |
| P9673_R03PAPPHOLD01 | None | None | View | |
| 9673 | OTHER | Yale University Cancer Center LAO | View | |
| 9673 | OTHER | CTEP | View | |
| N01CM00032 | NIH | None | https://reporter.nih.gov/quic… | View |
| N01CM00038 | NIH | None | https://reporter.nih.gov/quic… | View |
| N01CM00039 | NIH | None | https://reporter.nih.gov/quic… | View |
| N01CM00071 | NIH | None | https://reporter.nih.gov/quic… | View |
| N01CM00099 | NIH | None | https://reporter.nih.gov/quic… | View |
| N01CM00100 | NIH | None | https://reporter.nih.gov/quic… | View |
| P30CA016359 | NIH | None | https://reporter.nih.gov/quic… | View |
| U10CA180821 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186704 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186712 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186716 | NIH | None | https://reporter.nih.gov/quic… | View |