Follicular LymphomaPhase 2NCT04750941
Study of Copanlisib and Ketogenic Diet
A Phase 2 study testing Copanlisib and Ketogenic Diet in people with Follicular Lymphoma and Endometrial Cancer, run by Columbia University at 1 site in United States.
Trial summary
This is a multicenter, open label, pilot phase II study of the PI3K inhibitor copanlisib in combination with a ketogenic diet in the treatment of patients with one of the following malignancies: (a) relapsed or refractory (R/R) follicular lymphoma (FL), (b) R/R endometrial cancer (EC) with a documented activating… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma, Endometrial Cancer
- What is being tested?
- Copanlisib and Ketogenic Diet
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2022to 9 Jun 2023
- 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
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age or older on day of signing informed consent.
- For lymphoma, patients should have measurable disease based on the Lugano Criteria.
- For FL patients must have received at least two lines of prior therapy. There is no upper limit for the number of prior therapies. Tumor tissues of all patients are encouraged to be submitted (optional) prospectively for whole or targeted exome sequencing of key cancer related genes, using the Columbia Combined Cancer Panel (CCCP) or a comparable sequencing platform, such as the MSK-IMPACT 468-gene oncopanel.
- For EC the patients must have recurrent/advanced tumor for which surgical or the systemic curative treatments, or standard therapeutic approaches are not available. The following histologic subtypes are eligible: endometrioid, serous, clear cell, undifferentiated /dedifferentiated, mucinous, squamous, transitional, not-otherwise specified, and mixed celltype.
- Fresh and or archived tumor tissues must be available to (a) establish the diagnosis of the respective malignancies as described in Inclusion Criteria, and (b) be investigated for biomarkers. Patients without historical material or fresh tissue biopsy that is adequate for both diagnosis and correlative studies will not be eligible for the clinical trial.
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- Left Ventricular Ejection Fraction (LVEF) > 50%.
- A performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Demonstrate adequate organ function. All screening labs should be performed within 14 days of treatment initiation.
- HIV positive patients will be eligible as long as the viral load by polymerase chain reaction (PCR) testing is undetectable.
- Female patients of childbearing potential must have a negative pregnancy test within 7 days prior to treatment start.
- Adequate contraception.
Who cannot join
- The following treatments are prohibited: (a) Chemotherapy (including PI3K inhibitors and other approved or investigational drugs) and monoclonal antibody within 3 weeks; (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids that have not been stabilized (≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
- Patients that have not recovered from adverse events due to chemotherapy agents administered more than 3 weeks earlier.
- Hypersensitivity to copanlisib or any of its excipients.
- Type I diabetes
- Uncontrolled Type II diabetes mellitus (HbA1c> 7.5%).
- Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin.
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- Patients that received major surgery and have not recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Patients with active, clinically serious infections > CTCAE version 5 Grade 2.
- Patients with known active concurrent malignancy with the following exception: nonmelanoma skin cancer, prostatic intraepithelial neoplasia, or carcinoma in situ of the cervix, prostate cancer that responds to androgen deprivation therapy and has no progression of disease for at least 12 months. If there is a history of prior malignancy, the patient must be disease-free for ≥ 3 years.
- Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 150/90; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria.
- Concomitant use of strong CYP3A4 inhibitors (defined in the protocol).
- Uncontrolled moderate to severe hypertriglyceridemia (TG>300 mg/dL).
- Myocardial infarction within 6 months of cycle 1, day 1.
- Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see Appendix 5).
- An ECG recorded at screening showing evidence of cardiac ischemia.
- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 6 months before the start of study medication.
- Patients who are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through at least 30 days after the last dose of trial treatment.
- History of nephrolithiasis or nephrolithiasis incidentally discovered during CT screening. *Known selenium deficiency.
- Body mass index (BMI) less than 20.
- An allergy or intolerance to egg, gluten or milk protein.
- History of serious or uncontrolled gout or hyperuricemia.
- Pregnancy, lactation, or breastfeeding.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigators' opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
- Major surgical procedure or significant traumatic injury within 28 days prior to Day 1 or anticipation of the need for major surgery during the course of study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Pilot Phase II Study of the PI3K Inhibitor Copanlisib in Combination With a Ketogenic Diet in the Treatment of Patients With Relapsed or Refractory Follicular Lymphoma or Endometrial Cancer
This is a multicenter, open label, pilot phase II study of the PI3K inhibitor copanlisib in combination with a ketogenic diet in the treatment of patients with one of the following malignancies: (a) relapsed or refractory (R/R) follicular lymphoma (FL), (b) R/R endometrial cancer (EC) with a documented activating mutation in PIK3CA or loss of phosphatase and tensin homolog (PTEN).
Read the detailed description
As the investigators recently reported ketogenic diet can suppress hyperinsulinemia associated with PI3K inhibitors, leading to potentiation of the anti-tumor effects of PI3K inhibitors. Copanlisib potently inhibits PI3Kα and PI3Kδ. It has been approved for the treatment of relapsed follicular lymphoma, based on ORR of 59% (84 of 142 patients). The CR rate in FL was 14%, and the median progression-free survival was 11.2 months. Copanlisib demonstrated encouraging clinical activity in marginal zone lymphoma (ORR 70% including 9% CR). While these results are clinically meaningful, FL and MZL inevitably develop resistance to copanlisib with time, even in those patients who initially respond to the therapy. Novel strategies to improve the efficacy of copanlisib in FL and MZL, by improving CR and PFS, may transform how to manage these incurable malignancies.
- Conditions
- Follicular Lymphoma, Endometrial Cancer
- Being tested
- Copanlisib, Ketogenic Diet
- Keywords
- Keto diet, Copanlisib
- Medical subject headings
- Lymphoma, Follicular, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CopanlisibDrug
Also called Aliqopa
Copanlisib will be infused intravenously on days 1, 8, 15 of each cycle, over 1 hour, of 28-day cycles.
Ketogenic DietOther
In cycle 1, patients will first start the ketogenic diet for 7 days (Day -6 to Day 0).
Only the patients who demonstrate compliance and tolerance with the ketogenic diet, as confirmed by pertinent blood and urine tests and a diary of diet, will be allowed to continue the study and start copanlisib on Day 1. The ketogenic diet will continue daily throughout the treatment days.
In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1.
The ketogenic diet will then continue daily throughout the treatment days.
| Study group | Role | What they receive |
|---|---|---|
| Follicular Lymphoma (FL) | Experimental | The lymphoma study group will enroll 23 patients with FL.
In cycle 1, patients will first start ketogenic diet for 7 days (Day -6 to Day 0). Only patients who demonstrate compliance and tolerance with the ketogenic diet for all 7 days, as confirmed by pertinent blood and urine tests, will be allowed to continue the study and treatment using copanlisib and the ketogenic diet starting on Day 1. In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1. Receives: Drug: Copanlisib; Other: Ketogenic Diet |
| Endometrial Cancer (EC) | Experimental | The solid tumor group will enroll 19 patients with EC.
In cycle 1, patients will first start ketogenic diet for 7 days (Day -6 to Day 0). Only patients who demonstrate compliance and tolerance with the ketogenic diet for all 7 days, as confirmed by pertinent blood and urine tests, will be allowed to continue the study and treatment using copanlisib and the ketogenic diet starting on Day 1. In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1. Receives: Drug: Copanlisib; Other: Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR will be determined from the number of individuals with a complete response (CR) and number of individuals with a partial response (PR)
Measured: Up to 58 weeks or 4 weeks after the last dose
Secondary outcomes (4)
Complete Response (CR) Rate
Total number of participants with a CR.
Measured: Up to 58 weeks or 4 weeks after the last dose
Partial Response (PR) Rate
Total number of participants with a PR.
Measured: Up to 58 weeks or 4 weeks after the last dose
ORR at the Simon Stage I Analysis
ORR will be determined from the number of individuals with a complete response (CR) and number of individuals with a partial response (PR).
Measured: Up to 58 weeks or 4 weeks after the last dose
Patient Compliance With the Ketogenic Diet
Total # of patients who are compliant with the ketogenic diet.
Measured: Up to 58 weeks or 4 weeks after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2021
- Study start10 Feb 2022
- Primary completion9 Jun 2023
- Study completion9 Jun 2023
Why it stopped: Enrollment challenges
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 Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Jennifer Amengual, Columbia University
- Investigators
- Jennifer E. Amengual, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04750941
- Sponsor's protocol ID
- AAAS4953
- Status last verified
- Feb 2025
- First submitted
- 8 Feb 2021
- Last updated
- 4 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase II Study of the PI3K Inhibitor Copanlisib in Combination With a Ketogenic Diet in the Treatment of Patients With Relapsed or Refractory Follicular Lymphoma or Endometrial Cancer
- ClinicalTrials.gov ID
- NCT04750941
- Acronym / sponsor ID
- AAAS4953
- Conditions
- Follicular Lymphoma, Endometrial Cancer
- Keywords
- Keto diet, Copanlisib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment challenges
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 10 Feb 2022 (actual)
- Primary completion
- 9 Jun 2023 (actual)
- Study completion
- 9 Jun 2023 (actual)
- First posted
- 11 Feb 2021 (actual)
- Results
- Posted 4 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, open label, pilot phase II study of the PI3K inhibitor copanlisib in combination with a ketogenic diet in the treatment of patients with one of the following malignancies: (a) relapsed or refractory (R/R) follicular lymphoma (FL), (b) R/R endometrial cancer (EC) with a documented activating mutation in PIK3CA or loss of phosphatase and tensin homolog (PTEN).
Detailed description
As the investigators recently reported ketogenic diet can suppress hyperinsulinemia associated with PI3K inhibitors, leading to potentiation of the anti-tumor effects of PI3K inhibitors. Copanlisib potently inhibits PI3Kα and PI3Kδ. It has been approved for the treatment of relapsed follicular lymphoma, based on ORR of 59% (84 of 142 patients). The CR rate in FL was 14%, and the median progression-free survival was 11.2 months. Copanlisib demonstrated encouraging clinical activity in marginal zone lymphoma (ORR 70% including 9% CR). While these results are clinically meaningful, FL and MZL inevitably develop resistance to copanlisib with time, even in those patients who initially respond to the therapy. Novel strategies to improve the efficacy of copanlisib in FL and MZL, by improving CR and PFS, may transform how to manage these incurable malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Follicular Lymphoma (FL) | Experimental | Drug: Copanlisib, Other: Ketogenic DietThe lymphoma study group will enroll 23 patients with FL. In cycle 1, patients will first start ketogenic diet for 7 days (Day -6 to Day 0). Only patients who demonstrate compliance and tolerance with the ketogenic diet for all 7 days, as confirmed by pertinent blood and urine tests, will be allowed to continue the study and treatment using copanlisib and the ketogenic diet starting on Day 1. In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1. |
| Endometrial Cancer (EC) | Experimental | Drug: Copanlisib, Other: Ketogenic DietThe solid tumor group will enroll 19 patients with EC. In cycle 1, patients will first start ketogenic diet for 7 days (Day -6 to Day 0). Only patients who demonstrate compliance and tolerance with the ketogenic diet for all 7 days, as confirmed by pertinent blood and urine tests, will be allowed to continue the study and treatment using copanlisib and the ketogenic diet starting on Day 1. In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be willing and able to provide written informed consent for the trial.
- Be 18 years of age or older on day of signing informed consent.
- For lymphoma, patients should have measurable disease based on the Lugano Criteria.
- For FL patients must have received at least two lines of prior therapy. There is no upper limit for the number of prior therapies. Tumor tissues of all patients are encouraged to be submitted (optional) prospectively for whole or targeted exome sequencing of key cancer related genes, using the Columbia Combined Cancer Panel (CCCP) or a comparable sequencing platform, such as the MSK-IMPACT 468-gene oncopanel.
- For EC the patients must have recurrent/advanced tumor for which surgical or the systemic curative treatments, or standard therapeutic approaches are not available. The following histologic subtypes are eligible: endometrioid, serous, clear cell, undifferentiated /dedifferentiated, mucinous, squamous, transitional, not-otherwise specified, and mixed celltype.
Key exclusion criteria (25 listed)
- The following treatments are prohibited: (a) Chemotherapy (including PI3K inhibitors and other approved or investigational drugs) and monoclonal antibody within 3 weeks; (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids that have not been stabilized (≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs.
- Patients that have not recovered from adverse events due to chemotherapy agents administered more than 3 weeks earlier.
- Hypersensitivity to copanlisib or any of its excipients.
- Type I diabetes
- Uncontrolled Type II diabetes mellitus (HbA1c> 7.5%).
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 |
|---|---|---|
| CopanlisibAlso: AliqopaCopanlisib will be infused intravenously on days 1, 8, 15 of each cycle, over 1 hour, of 28-day cycles. | Drug | Endometrial Cancer (EC), Follicular Lymphoma (FL) |
| Ketogenic DietIn cycle 1, patients will first start the ketogenic diet for 7 days (Day -6 to Day 0). Only the patients who demonstrate compliance and tolerance with the ketogenic diet, as confirmed by pertinent blood and urine tests and a diary of diet, will be allowed to continue the study and start copanlisib on Day 1. The ketogenic diet will continue daily throughout the treatment days. In cycle 2 and beyond, patients will start the ketogenic diet and copanlisib on day 1. The ketogenic diet will then continue daily throughout the treatment days. | Other | Endometrial Cancer (EC), Follicular Lymphoma (FL) |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 58 weeks or 4 weeks after the last dose
ORR will be determined from the number of individuals with a complete response (CR) and number of individuals with a partial response (PR)
4 secondary outcomes
Complete Response (CR) Rate
Time frame: Up to 58 weeks or 4 weeks after the last dose
Partial Response (PR) Rate
Time frame: Up to 58 weeks or 4 weeks after the last dose
ORR at the Simon Stage I Analysis
Time frame: Up to 58 weeks or 4 weeks after the last dose
Patient Compliance With the Ketogenic Diet
Time frame: Up to 58 weeks or 4 weeks after the last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Jennifer E. Amengual, MD principal investigator
Columbia University
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 Ketogenic Diet in people with Follicular Lymphoma and Endometrial Cancer, run by Columbia University 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 12 inclusion and 25 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 4 Mar 2025. 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 4 Mar 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?
Objective Response Rate (ORR) (time frame: Up to 58 weeks or 4 weeks after the last dose). 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 4 Mar 2025.