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Platinum-Refractory Fallopian Tube CarcinomaPhase 2NCT05295589

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

A Phase 2 study testing Computed Tomography, Copanlisib Hydrochloride and Magnetic Resonance Imaging in people with Platinum-Refractory Fallopian Tube Carcinoma and Platinum-Refractory Ovarian Carcinoma, run by National Cancer Institute (NCI) at 5 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Computed Tomography, Copanlisib Hydrochloride and Magnetic Resonance Imaging
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
5 sitesUnited States
Study dates
30 Jun 2022to 17 Mar 2023
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 34Show fewer
  • 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])
  • Age >= 18
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2
  • Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
  • Hemoglobin >= 10 g/dL (within 14 days prior to registration)
  • Platelets >= 100,000/mcL (within 14 days prior to registration)
  • Creatinine clearance (CrCL) >= 51 mL/min (estimated using Cockcroft-Gault equation) (within 14 days prior to registration)
  • Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN (within 14 days prior to registration)
  • Lipase =< 1.5 x ULN within 14 days of registration
  • International normalized ratio (INR) =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 times the upper limit of normal within 14 days of registration
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
  • Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that their medication dose and INR/PTT is stable. Oral anticoagulants are allowed provided there are no interactions
  • The effects of copanlisib and olaparib on the developing human fetus are unknown. For this reason and because maternal toxicity, developmental toxicity and teratogenic effects have been observed in nonclinical studies and PI3K inhibitors agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 1 month after the last dose of copanlisib and/or olaparib. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
  • Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and must be off steroids and stable at least one month
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Who cannot join

  • 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
Show all 22Show fewer
  • 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:
  • Persistent grade >= 2 adverse events due to prior anti-cancer therapy with the exception of alopecia, hypothyroidism requiring medication, vitiligo, and the laboratory values defined in the inclusion criteria.
  • Known psychiatric illness/social situations that would limit compliance with study requirements.
  • History of or current autoimmune disease
  • Non-healing wound, ulcer, or bone fracture
  • Active, clinically serious infections > grade 2 (CTCAE v5.0)
  • Women who are pregnant or unwilling to discontinue nursing
  • Patients who have a history of non-infectious pneumonitis/interstitial lung disease (ILD) that required steroids, or current non-infectious pneumonitis/ILD

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

Other trials in United States

About this study

Official title: A Randomized Phase II Trial Comparing the Combination of PI3K Inhibitor Copanlisib (BAY 80-6946) and PARP Inhibitor Olaparib (AZD2281) to Standard Chemotherapy in Patients With Recurrent Platinum Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Progressed Through Prior PARP Inhibitor Therapy

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the clinical efficacy of the combination of copanlisib/olaparib, as measured by investigator-assessed progression free survival (PFS), compared to standard chemotherapy in the setting of recurrent platinum resistant ovarian cancer that has progressed through prior PARP inhibitor therapy.

SECONDARY OBJECTIVES:

  1. To assess the clinical efficacy of the combination of copanlisib/olaparib, as measured by objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To assess the clinical efficacy of the combination of copanlisib/olaparib, as measured by overall survival (OS), compared to standard chemotherapy in the setting of recurrent platinum resistant ovarian cancer that has progressed through prior PARP inhibitor therapy.

III. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0 for each treatment arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive either paclitaxel intravenously (IV) OR pegylated liposomal doxorubicin hydrochloride IV, OR topotecan hydrochloride IV while on study.

ARM II: Patients receive copanlisib hydrochloride IV and olaparib orally (PO) while on study.

Patients undergo computed tomography (CT) scan while on study and may undergo magnetic resonance imaging (MRI) throughout the study.

Being tested
Computed Tomography, Copanlisib Hydrochloride, Magnetic Resonance Imaging, Olaparib, Paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Copanlisib HydrochlorideDrug

    Also called 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

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • OlaparibDrug

    Also called AZD 2281, AZD-2281, AZD2281, KU-0059436

    Given PO

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Pegylated Liposomal Doxorubicin HydrochlorideDrug

    Also called ATI-0918, Caelyx, Dox-SL, Doxil

    Given IV

  • Topotecan HydrochlorideDrug

    Also called Hycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl

    Given IV

Study groups in NCT05295589
Study groupRoleWhat they receive
Arm I (standard of care chemotherapy)Active comparatorPatients 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.
Receives: Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Topotecan Hydrochloride
Arm II (copanlisib, olaparib)ExperimentalPatients receive copanlisib hydrochloride IV and olaparib PO while on study. Patients undergo CT scan while on study and may undergo MRI throughout the study.
Receives: Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (3)

  1. Objective response rate (ORR)

    Defined as the binomial proportion of evaluable patients with a best overall response of complete response (CR) or partial response (PR) (by Response Evaluation Criteria in Solid Tumors 1.1). Responses reported by the treating physician will be used for these analyses. The ORR estimates by treatment arm will be supported by their 2-sided, 95% Wilson-Score confidence intervals (Wilson, 1927, Agresti, 1998). The relative odds of response in the experimental group (vs. the reference group) will be estimated using a multivariable logistic regression model specified with main effects for the treatment group and covariate adjustments for the stratification factors reported at baseline.

    Measured: Up to 5 years

  2. Overall survival (OS)

    The OS treatment hypothesis test will be based on a logrank test, stratified by the factors specified at randomization. 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 vs Arm 1) and covariate adjustment for the stratification factors used in the randomization.

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

  3. Incidence of adverse events

    The nature, frequency, and degree of toxicity will be tabulated at the System Organ Class and adverse event-specific term levels using Common Terminology Criteria for Adverse Events version 5.0. Each patient will be represented according to the maximum grade observed for each term. Tabulations will show the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2022
  2. Study start30 Jun 2022 (estimated)
  3. Primary completion17 Mar 2023 (estimated)
  4. Study completion17 Mar 2023 (estimated)

Why it stopped: Drug supply issues

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05295589
Sponsor's protocol ID
NCI-2022-02228
Other IDs
NCI-2022-02228, NRG-GY029, NRG-GY029, U10CA180868
Status last verified
Sep 2023
First submitted
23 Mar 2022
Last updated
26 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Computed Tomography, Copanlisib Hydrochloride and Magnetic Resonance Imaging in people with Platinum-Refractory Fallopian Tube Carcinoma and Platinum-Refractory Ovarian Carcinoma, run by National Cancer Institute (NCI) at 5 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?

The sponsor lists 34 inclusion and 22 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression free survival (PFS) (time frame: Time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years). 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 NCT05295589.

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 26 Sep 2023.

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