Ignite Creation Date:
2025-12-25 @ 3:29 AM
Ignite Modification Date:
2025-12-26 @ 2:10 AM
Study NCT ID:
NCT04317105
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-24
First Post:
2020-03-20
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Immunotherapy (Nivolumab With or Without Ipilimumab) in Patients With Advanced Solid Cancers That Have Changes in the Following Genes: PIK3CA and PTEN
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12
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 I/II trial studies the side effects and best dose of copanlisib when given together with nivolumab and ipilimumab and to see how well they work in treating patients with solid cancers that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and have changes in PIK3CA and PTEN genes. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. The addition of copanlisib to usual immunotherapy may work better in treating patients with solid cancers compared to usual immunotherapy alone.
Detailed Description:
PRIMARY OBJECTIVE:
I. To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors.
SECONDARY OBJECTIVES:
I. To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response (OR) = complete response (CR) + partial response (PR).
III. To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
IV. To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
V. To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumor deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; Ib. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.
TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or computed tomography (CT) scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo echocardiography (ECHO) during screening and as clinically indicated on study.
TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
I. To evaluate safety and confirm the combination recommended phase 2 dose (RP2D) of the combination of copanlisib, nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors.
SECONDARY OBJECTIVES:
I. To observe and record antitumor activity. II. To assess clinical benefit of copanlisib in combination with nivolumab (and ipilimumab) in patients with molecularly-selected advanced solid tumors, as measured by objective response (OR) = complete response (CR) + partial response (PR).
III. To assess overall duration of response (DoR), progression free survival (PFS), and overall survival (OS).
IV. To assess immune-modulatory changes associated with copanlisib-induced PI3K inhibition and combination of copanlisib and nivolumab (and ipilimumab).
V. To correlate molecular alterations in the PI3K-AKT pathway and treatment induced immune-modulatory changes with objective response (OR).
EXPLORATORY OBJECTIVES:
I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES), ribonucleic acid (RNA) sequencing, reverse phase protein array (RPPA), circulating tumor deoxyribonucleic acid (DNA) analysis, and immune profiling in order to:
Ia. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned; Ib. Identify resistance mechanisms using genomic DNA- and RNA-based assessment platforms.
II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research.
III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.
OUTLINE: This is a phase I, dose-escalation study of copanlisib followed by a phase II study. Patients are assigned to 1 of 2 trials.
TRIAL I: Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or computed tomography (CT) scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo echocardiography (ECHO) during screening and as clinically indicated on study.
TRIAL II: Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 of cycle 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 1 and ipilimumab IV over 90 minutes every 8 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and/or CT scan during screening and every 8 weeks, as well as a tumor biopsy at baseline, cycle 1 day 15, cycle 2 day 15, and every 3 weeks thereafter, and at disease progression. Patients also undergo blood sample collection at baseline, cycle 1 days 8 and 15, cycle 2 day 15, cycle 4 day 1 and disease progression. Patients undergo ECHO during screening and as clinically indicated on study.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 2 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: