Endometrial CancerPhase 2NCT05082025
Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations
A Phase 2 study testing Copanlisib and fulvestrant in people with Endometrial Cancer and Ovarian Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid tumors harboring alterations that activate the Phosphatidylinositol-3 kinase (PI3K) pathway. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endometrial Cancer, Ovarian Cancer
- What is being tested?
- Copanlisib and fulvestrant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Sep 2022to 12 Dec 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed ER+ and/or PR+ advanced or metastatic solid cancer including ovarian cancer (cohort 1), endometrial cancer (cohort 2), or breast cancer (cohort 3) (Figure 1). ER and/or PR positivity is defined as >10% immunohistochemical staining of any intensity. Cohort 3 will be enriched to include at least 7 patients naive to any PI3Ki in Stage 1 and also in Stage 2.
- Presence of one or more PI3K and/or PTEN alterations in tumor tissue. Genetic alterations will include PIK3CA gain of function mutations, PIK3R1 loss of function mutations, PTEN loss of function mutations, and PTEN deletions.
- Measurable disease per the RECIST 1.1.
- The patient (or legally acceptable representative, if applicable) provides written informed consent for the study.
- Female or male ≥18 years of age on the day of informed consent signing.
- Patients have no available standard therapy known to prolong survival. For cohort 3 only, prior treatment with aPI3Ki or everolimus is not required and patients with or without prior PI3Ki or everolimus will be qualified for enrollment
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- Adequate archived tumor tissue for the analysis for PI3K and PTEN alterations if available.
- Eastern Cooperative Oncology Group (ECOG) performance status of .2.
- Adequate organ and marrow function as defined below:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥1.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Total bilirubin (TB) ≤1.5 × institutional upper limit of normal (ULN); Patients with known Gilbert's disease who have TB ≤3 × ULN may be enrolled)
- Aspartate transaminase (AST)/ alanine transaminase (ALT) ≤3 × ULN. If patient has liver metastases, AST and ALT ≤5.0 × ULN.
- Creatinine ≤1.5 x ULN
- International normalized ratio ≤1.5.
- Fasting blood glucose ≤140 mg/dL and hemoglobin A1c ≤8.5% (both criteria have to be met).
- Cardiac ejection fraction ≥45%.
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 14 days prior to the initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential (WOCBP) must agree and commit to the use of 2 highly effective methods of birth control throughout the duration of the study until at least 150 days following the last dose of study drug. Acceptable methods are defined as those that result, alone or in combination, in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as surgical sterilization, an intrauterine device, or hormonal contraception in combination with a barrier method. Women using systemically acting hormonal contraceptives should add a barrier method. In certain countries (if permitted by law), WOCBP may agree to abide by heterosexual sexual abstinence during the time of participation in this study.
- Male patients and their female partners of childbearing potential must agree and commit to use a barrier contraception (eg, condom with spermicidal foam/gel/film/cream/suppository) throughout the duration of the study until at least 90 days following the last dose of study drug, in addition to their female partners using either an intrauterine device or hormonal contraception and continuing until at least 90 days following the last dose of study drug. This criterion may be waived for male patients who have had a vasectomy > 6 months before signing the ICF.
- Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
Who cannot join
- The patient has central nervous system (CNS) involvement. If the patient fulfills the following 3 criteria, she/he is eligible for the study:
- Completed prior therapy (including radiation and/or surgery) for CNS metastases, and
- CNS tumor is radiologically stable for ≥ 28 days prior to study start, and
- The patient is not receiving steroids and enzyme-inducing antiepileptic medications for brain metastases.
- Patients with HER2 positive breast cancer.
- Patients must be ≥4 weeks or at least 5 half-lives beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents at the time of treatment initiation.
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- NOTE: If the patient received major surgery, she/he must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the study treatment.
- Prior treatment with fulvestrant or any PI3Ki for cohorts 1 and 2.
- Known hypersensitivity to copanlisib or fulvestrant, or to any of the excipients of copanlisib or fulvestrant.
- Concomitant use of strong cytochrome P450 (CYP)3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) or inhibitors (e.g., ritonavir, saquinavir, nelfinavir, boceprevir, telaprevir, ketoconazole, omeprazole). Use of strong inhibitors and/or inducers of CYP3A4 is not permitted from Day -14 of Cycle 1 until the start of the study intervention.
- The patient is currently receiving warfarin or other coumarin derived anticoagulants for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin, fondaparinux, or direct oral anticoagulants such as rivaroxaban or apixaban is allowed.
- Known additional malignancy that is progressing or requires active treatment.
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient fs participation for the full duration of the study or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Known history of human immunodeficiency virus infection.
- History or current symptomatic pneumonitis.
- Has clinically significant, uncontrolled heart disease and/or recent cardiac events, including any of the following:
- History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
- History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months
- Uncontrolled hypertension defined by a systolic blood pressure (BP) ≥140 mmHg and/or diastolic BP ≥90 mmHg, with or without antihypertensive medication over the course of one clinic visit at intervals of ≥30 minutes. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
- Type 1 diabetes mellitus.
- Uncontrolled type 2 diabetes mellitus.
- Positive cytomegalovirus (CMV) polymerase chain reaction (PCR) test at baseline.
- Active hepatitis B virus (HBV; chronic or acute; defined as having a known positive hepatitis B surface antigen [HbsAg] test at the time of screening) or hepatitis C infection requiring treatment.
- Participants with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HbcAb] and absence of HbsAg) are eligible if HBV DNA is negative.
- Participants with positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid tumors harboring alterations that activate the Phosphatidylinositol-3 kinase (PI3K) pathway.
Read the detailed description
Part 1: Dose confirmation:
Primary Objective:
- To evaluate the safety, tolerability, and dose-limiting toxicities (DLT) of copanlisib 60 mg administered intravenously (IV) on Days 1, 8 and 15 in combination with fulvestrant 500 mg administered intramuscularly (IM) on Day 1 and Day 15 of Cycle 1, and then on Day 1 of each subsequent 28-day cycle to confirm the recommended phase 2 doses (RP2D) of the combination therapy.
Secondary objective:
- To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined in Part 2 by evaluating the objective response rate (ORR).
- To evaluate additional efficacy measures such as progression-free survival (PFS) and overall survival (OS) of copanlisib in combination with fulvestrant.
Exploratory Objectives:
- To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing circulating tumor DNA (ctDNA) as outlined in Part 2.
Part 2: Dose expansion:
Primary objectives:
- To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined above by evaluating the objective response rate (ORR). Patients enrolled for Part 1 will be included in this efficacy analysis.
Secondary Objectives:
- To evaluate additional efficacy measures such as PFS and OS of copanlisib in combination with fulvestrant.
- To evaluate the safety and tolerability of copanlisib in combination with fulvestrant.
Exploratory Objectives:
- To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing ctDNA.
- Conditions
- Endometrial Cancer, Ovarian Cancer
- Being tested
- Copanlisib, fulvestrant
- Medical subject headings
- Endometrial Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CopanlisibDrug
Given by IV
fulvestrantDrug
Given by IM
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose confirmation | Experimental | Up to 6 evaluable patients to confirm a single combination dose of copanlisib and fulvestrant Receives: Drug: Copanlisib; Drug: fulvestrant |
| Part 2: Dose expansion: | Experimental | The dose expansion part will enroll in 3 indication-specific cohorts with 13 to 26 patients Receives: Drug: Copanlisib; Drug: fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
A DLT is defined as an intervention-related adverse event that impedes a patient from dosing a full cycle of copanlisib (3 doses), a delay of over 1 week in intitated study intervention occurring secondary to any study related adverse event, or death not clearly attrubuted to an underlying disease or alternate cause. Six out of the seven treated patients were evaluable for DLT. One patient was not evaluable for DLT due to not completing a full cycle of treatment within the first 28-days of treatment.
Measured: Within the first cycle (28-days) of treatment.
Number of Participants With Treatment-related Adverse Events
Treatment-related adverse events that were deemed as possibly, probably, or definitely related to treatment, and were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. All treatment-related adverse events were captured from the time of signing consent through 30 days after the last dose of study drug or initation of a new anticancer therapy, whichever occurred first. The number of patients experiencing each treatment related adverse event (at least once) is reported.
Measured: Through study completion, an average of 14 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start27 Sep 2022
- Primary completion3 May 2024
- Study completion12 Dec 2025
Why it stopped: Copanlisib development was discontinued by Bayer following withdrawal of copanlisib in relapsed follicular lymphoma in November 2023.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Timothy Yap, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05082025
- Sponsor's protocol ID
- 2020-1241
- Other IDs
- NCI-2021-09936
- Status last verified
- Dec 2025
- First submitted
- 2 Sep 2021
- Last updated
- 9 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations
- ClinicalTrials.gov ID
- NCT05082025
- Acronym / sponsor ID
- 2020-1241
- Conditions
- Endometrial Cancer, Ovarian Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Copanlisib development was discontinued by Bayer following withdrawal of copanlisib in relapsed follicular lymphoma in November 2023.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 27 Sep 2022 (actual)
- Primary completion
- 3 May 2024 (actual)
- Study completion
- 12 Dec 2025 (actual)
- First posted
- 18 Oct 2021 (actual)
- Results
- Posted 11 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of copanlisib in combination with fulvestrant in advanced hormone receptor-positive (HR+) solid tumors harboring alterations that activate the Phosphatidylinositol-3 kinase (PI3K) pathway.
Detailed description
Part 1: Dose confirmation:
Primary Objective:
- To evaluate the safety, tolerability, and dose-limiting toxicities (DLT) of copanlisib 60 mg administered intravenously (IV) on Days 1, 8 and 15 in combination with fulvestrant 500 mg administered intramuscularly (IM) on Day 1 and Day 15 of Cycle 1, and then on Day 1 of each subsequent 28-day cycle to confirm the recommended phase 2 doses (RP2D) of the combination therapy.
Secondary objective:
- To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined in Part 2 by evaluating the objective response rate (ORR).
- To evaluate additional efficacy measures such as progression-free survival (PFS) and overall survival (OS) of copanlisib in combination with fulvestrant.
Exploratory Objectives:
- To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing circulating tumor DNA (ctDNA) as outlined in Part 2.
Part 2: Dose expansion:
Primary objectives:
- To assess the efficacy of copanlisib administered in combination with fulvestrant as outlined above by evaluating the objective response rate (ORR). Patients enrolled for Part 1 will be included in this efficacy analysis.
Secondary Objectives:
- To evaluate additional efficacy measures such as PFS and OS of copanlisib in combination with fulvestrant.
- To evaluate the safety and tolerability of copanlisib in combination with fulvestrant.
Exploratory Objectives:
- To investigate target engagement, clonal evolution, and mechanisms of resistance using tissue and liquid biopsies utilizing ctDNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose confirmation | Experimental | Drug: Copanlisib, Drug: fulvestrantUp to 6 evaluable patients to confirm a single combination dose of copanlisib and fulvestrant |
| Part 2: Dose expansion: | Experimental | Drug: Copanlisib, Drug: fulvestrantThe dose expansion part will enroll in 3 indication-specific cohorts with 13 to 26 patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologically confirmed ER+ and/or PR+ advanced or metastatic solid cancer including ovarian cancer (cohort 1), endometrial cancer (cohort 2), or breast cancer (cohort 3) (Figure 1). ER and/or PR positivity is defined as >10% immunohistochemical staining of any intensity. Cohort 3 will be enriched to include at least 7 patients naive to any PI3Ki in Stage 1 and also in Stage 2.
- Presence of one or more PI3K and/or PTEN alterations in tumor tissue. Genetic alterations will include PIK3CA gain of function mutations, PIK3R1 loss of function mutations, PTEN loss of function mutations, and PTEN deletions.
- Measurable disease per the RECIST 1.1.
- The patient (or legally acceptable representative, if applicable) provides written informed consent for the study.
- Female or male ≥18 years of age on the day of informed consent signing.
Key exclusion criteria (28 listed)
- The patient has central nervous system (CNS) involvement. If the patient fulfills the following 3 criteria, she/he is eligible for the study:
- Patients with HER2 positive breast cancer.
- Patients must be ≥4 weeks or at least 5 half-lives beyond treatment with any chemotherapy or other investigational therapy including hormonal, biological, or targeted agents at the time of treatment initiation.
- Prior treatment with fulvestrant or any PI3Ki for cohorts 1 and 2.
- Known hypersensitivity to copanlisib or fulvestrant, or to any of the excipients of copanlisib or fulvestrant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CopanlisibGiven by IV | Drug | Part 1: Dose confirmation, Part 2: Dose expansion: |
| fulvestrantGiven by IM | Drug | Part 1: Dose confirmation, Part 2: Dose expansion: |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: Within the first cycle (28-days) of treatment.
A DLT is defined as an intervention-related adverse event that impedes a patient from dosing a full cycle of copanlisib (3 doses), a delay of over 1 week in intitated study intervention occurring secondary to any study related adverse event, or death not clearly attrubuted to an underlying disease or alternate cause. Six out of the seven treated patients were evaluable for DLT. One patient was not evaluable for DLT due to not completing a full cycle of treatment within the first 28-days of treatment.
Number of Participants With Treatment-related Adverse Events
Time frame: Through study completion, an average of 14 weeks.
Treatment-related adverse events that were deemed as possibly, probably, or definitely related to treatment, and were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. All treatment-related adverse events were captured from the time of signing consent through 30 days after the last dose of study drug or initation of a new anticancer therapy, whichever occurred first. The number of patients experiencing each treatment related adverse event (at least once) is reported.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Yap, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Copanlisib and fulvestrant in people with Endometrial Cancer and Ovarian Cancer, run by M.D. Anderson Cancer Center at 1 site 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 21 inclusion and 28 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: stopped early, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 11 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dose Limiting Toxicity (DLT) (time frame: Within the first cycle (28-days) of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2026.