Comparing Standard of Care Chemotherapy Treatment to the Combination of Copanlisib and Olaparib for Recurrent Platinum Resistant Ovarian Cancer That Has Progressed Through PARP Inhibitor Therapy

NCT05295589 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2022-02228NRG-GY029U10CA180868
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial compares copanlisib and olaparib to standard of care chemotherapy in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that did not respond to previous platinum-based chemotherapy (platinum resistant) and that has come back (recurrent). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving copanlisib and olaparib may extend the time that the cancer does not progress compared to standard of care chemotherapy in patients with recurrent platinum resistant ovarian, fallopian tube, or primary peritoneal cancer.

Conditions

Platinum-Refractory Fallopian Tube Carcinoma; Platinum-Refractory Ovarian Carcinoma; Platinum-Refractory Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Endometrioid Adenocarcinoma; Recurrent Fallopian Tube High Grade Serous Adenocarcinoma; Recurrent Ovarian Endometrioid Adenocarcinoma; Recurrent Ovarian High Grade Serous Adenocarcinoma; Recurrent Platinum-Resistant Fallopian Tube Carcinoma; Recurrent Platinum-Resistant Ovarian Carcinoma; Recurrent Platinum-Resistant Primary Peritoneal Carcinoma; Recurrent Primary Peritoneal Endometrioid Adenocarcinoma; Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  The interim and primary analyses of PFS will be based on a logrank test, stratified by the factors declared at randomization. These analyses will include all patients enrolled onto the study regardless of compliance to their assigned study regimen. Patients will be grouped by their randomized treatment for intention-to-treat analyses. For the purposes of the primary analyses, the documentation of disease progression will be determined by the treating physician. The treatment hazard ratios and their 95% confidence intervals will be estimated using a multivariable proportional hazards model specified with main effects for the randomized treatment assignment (Arm 2 versus \[vs\] Arm 1) and covariate adjustment for the stratification factors declared at randomization.

  Time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Secondary Outcomes (3)

• Objective response rate (ORR)

  Up to 5 years

• Overall survival (OS)

  Time from study entry to time of death or the date of last contact, assessed up to 5 years

• Incidence of adverse events

  Up to 5 years

Study Arms (2)

Arm I (standard of care chemotherapy)

ACTIVE COMPARATOR

Patients receive either paclitaxel IV OR pegylated liposomal doxorubicin hydrochloride IV, OR topotecan hydrochloride IV while on study. Patients undergo CT scan while on study and may undergo MRI throughout the study.

Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Topotecan Hydrochloride

Arm II (copanlisib, olaparib)

EXPERIMENTAL

Patients receive copanlisib hydrochloride IV and olaparib PO while on study. Patients undergo CT scan while on study and may undergo MRI throughout the study.

Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Olaparib

Interventions

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm I (standard of care chemotherapy); Arm II (copanlisib, olaparib)

Copanlisib Hydrochloride DRUG

Given IV

Also known as: 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride

Arm II (copanlisib, olaparib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Arm I (standard of care chemotherapy); Arm II (copanlisib, olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Arm II (copanlisib, olaparib)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (standard of care chemotherapy)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: ATI-0918, Caelyx, Dox-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, Liposomal Doxorubicin Hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99

Arm I (standard of care chemotherapy)

Topotecan Hydrochloride DRUG

Given IV

Also known as: Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)

Arm I (standard of care chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent ovarian cancer. Ovarian cancer = fallopian tube cancer, ovarian cancer, primary peritoneal cancer. The following histology types are eligible:
• High grade serous
• Endometrioid, grade 3
• Any histology with BRCA1 and/or BRCA2 deleterious mutation (germline or somatic)
• Histologic confirmation of the original primary tumor is required via the pathology report (upload of report required)
• Confirmation of BRCA1 and BRCA2 germline status is required for all entered patients (upload of report\[s\] required)
• Tumor/somatic genomic testing can be provided or entered as not done (upload of report\[s\] required)
• Homologous recombination deficiency (HRD) testing can be provided or entered as not done (upload of report\[s\] required)
• Genetic/genomic testing results and HRD testing results, initially entered as not done, should be uploaded if they become available anytime during conduct of the study
• Participants must have progressed by imaging while receiving PARP inhibitor therapy (irrespective of whether PARP inhibitor therapy was given as maintenance therapy or as primary recurrence therapy); rising CA125 only is not considered as evidence of progression
• Platinum-resistant disease, defined as progression within \< 6 months from completion of platinum-based therapy, and inclusive of platinum refractory disease. The date should be calculated from the last administered dose of platinum therapy
• Unlimited lines of cytotoxic therapy allowed in the platinum-sensitive setting; =\< 2 lines of cytotoxic therapy allowed in the platinum-resistant setting
• Hormonal therapy (e.g., tamoxifen, aromatase inhibitors) will not count as a previous line of therapy
• Prior use of bevacizumab in the upfront or recurrent setting is required
• Participants must have evaluable disease - defined as RECIST 1.1 measurable disease OR non-measurable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related in the setting of a CA125 \> 2 x upper limit of normal \[ULN\])

You may not qualify if:

• Prior therapy:
• No chemotherapy or radiotherapy within 4 weeks of registration
• No hormonal therapy within 2 weeks of registration. Patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions
• No investigational agents within 4 weeks of registration
• No prior PI3K-AKT-mTOR pathway inhibitor therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, copanlisib, or other agents used in this study
• Copanlisib and olaparib are primarily metabolized by CYP3A4. Therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted from 14 days prior to registration until the end of the study
• Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study. Patients may be using topical or inhaled corticosteroids
• Use of concomitant herbal medications/preparations (except for vitamins), alternative/complimentary medications, immunosuppressive therapy, or other prohibited medications
• Patients with uncontrolled type I or II diabetes mellitus; uncontrolled diabetes is defined as glycosylated hemoglobin (HbAlc) \> 8.5%
• Patients with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months before registration
• Gastrointestinal conditions that would preclude consumption (swallowing), retention, and/or absorption of oral medications
• Patients with drainage gastrostomy tube are not allowed
• Patients with dependency on IV hydration or total parenteral nutrition (TPN) are not allowed
• Patients with uncontrolled intercurrent illness, including but not limited to:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (5)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

MeSH Terms

Interventions

copanlisib; Magnetic Resonance Spectroscopy; olaparib; Paclitaxel; Taxes; liposomal doxorubicin; Doxorubicin; Topotecan

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Panagiotis A Konstantinopoulos

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: March 25, 2022
• Study Start: June 30, 2022
• Primary Completion: March 17, 2023
• Study Completion: March 17, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

US (5)