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
A Phase I/II Biomarker Driven Combination Trial of Copanlisib and Immune Checkpoint Inhibitors in Patients With Advanced Solid Tumors
4 other identifiers
interventional
54
2 countries
6
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2020
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 20, 2020
CompletedFirst Posted
Study publicly available on registry
March 23, 2020
CompletedStudy Start
First participant enrolled
July 17, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 6, 2027
ExpectedMay 13, 2026
May 1, 2026
5.2 years
March 20, 2020
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events and serious adverse events
Adverse events and serious adverse events will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
At 30 days after last dose of study drug and every 3-6 months for up to 2 years
Incidence of dose limiting toxicities (DLTs)
Toxicities will be graded using NCI CTCAE version 5.0.
Up to first 2 cycles (each cycle is 28 days)
Secondary Outcomes (4)
Objective response (OR) rate (complete response [CR] + partial response [PR])
Up to 2 years post-treatment
Clinical benefit rate (OR + stable disease [SD] > 6 months)
Up to 2 years post-treatment
Progression free survival (PFS)
Until disease progression, start of a new cancer therapy, or up to 2 years after the last dose of study drugs, whichever comes first
Overall survival (OS)
Until disease progression, start of a new cancer therapy, or up to 2 years after the last dose of study drugs, whichever comes first
Other Outcomes (6)
Change in tumor immune microenvironment with copanlisib alone and with combination of copanlisib, nivolumab and ipilimumab
Baseline up to 2 years post-treatment
Change in circulating cytokines with copanlisib alone and with combination of copanlisib, nivolumab and ipilimumab
Baseline up to 2 years post-treatment
Correlation of immuno-modulatory changes with presence or absence of OR to the triplet combination
Up to 2 years post-treatment
- +3 more other outcomes
Study Arms (2)
Trial I (copanlisib, nivolumab)
EXPERIMENTALPatients 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. 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.
Trial II (copanlisib, nivolumab, ipilimumab)
EXPERIMENTALPatients 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.
Interventions
Undergo a tumor biopsy
Undergo blood sample collection
Undergo a CT scan
Given IV
Undergo ECHO
Given IV
Given IV
Undergo an x-ray
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective
- Patients must be \>= 4 weeks beyond treatment with any chemotherapy or other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of copanlisib in combination with nivolumab (and ipilimumab) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- Absolute neutrophil count (ANC) \>= 1,500 /mcL
- Platelets \>= 100,000 / mcL
- Hemoglobin \>= 9 g/dL
- Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (creatinine clearance should be calculated per institutional standard)
- Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases
- International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Patients must have a glycosylated hemoglobin (HbA1c) =\< 8.5% at screening and a fasting glucose of =\< 160 mg/dL
- Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test within 24 hours of study enrollment unless prior tubal ligation (\>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study. Sexually active patients must agree to use dual contraception for the duration of study participation and for 7 months after the last dose of study treatment for women of childbearing potential and 5 months for men with partners that are women of childbearing potential
- +4 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents
- Pregnant or breastfeeding women will be excluded from participation in this trial, as there is no significant clinical information regarding the effects of copanlisib, nivolumab, and ipilimumab on a fetus or newborn infant
- Known active hepatitis B or hepatitis C infection. All patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to study drug start using the routine hepatitis virus lab panel. Patients positive for hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus core antibody (HBcAb) will be eligible if they are negative for HBV DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV RNA
- Human immunodeficiency virus (HIV)-infected (HIV1/2 antibody-positive) patients may participate IF they meet all the following eligibility requirements:
- They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on this same regimen; the most recent undetectable viral load must be within the past 12 weeks
- They must have a CD4 count \>= 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/ mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy-induced bone marrow suppression
- For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy
- They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of enrollment
- They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
- Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization
- Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. Exceptions include vitiligo, type I diabetes mellitus, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids, Sjogren's syndrome
- Inability to comply with the study and follow-up procedures
- History of cerebrovascular accident (CVA), myocardial infarction, or unstable angina within the previous 6 months before starting therapy
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone curative therapy, or in situ cervical cancer
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Texas at Austin
Austin, Texas, 78712, United States
University of Texas Medical Branch
Galveston, Texas, 77555-0565, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy A Yap
University of Texas MD Anderson Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 20, 2020
First Posted
March 23, 2020
Study Start
July 17, 2020
Primary Completion
October 1, 2025
Study Completion (Estimated)
May 6, 2027
Last Updated
May 13, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.