Study of Copanlisib and Ketogenic Diet

NCT04750941 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAS4953
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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 mutation in PIK3CA or loss of phosphatase and tensin homolog (PTEN).

Conditions

Follicular Lymphoma; Endometrial Cancer

Keywords

Keto diet; Copanlisib

Outcome Measures

Primary Outcomes (1)

• 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)

  Up to 58 weeks or 4 weeks after the last dose

Secondary Outcomes (4)

• Complete Response (CR) Rate

  Up to 58 weeks or 4 weeks after the last dose

• Partial Response (PR) Rate

  Up to 58 weeks or 4 weeks after the last dose

• ORR at the Simon Stage I Analysis

  Up to 58 weeks or 4 weeks after the last dose

• Patient Compliance With the Ketogenic Diet

  Up to 58 weeks or 4 weeks after the last dose

Study Arms (2)

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.

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.

Drug: Copanlisib; Other: Ketogenic Diet

Interventions

Copanlisib DRUG

Copanlisib will be infused intravenously on days 1, 8, 15 of each cycle, over 1 hour, of 28-day cycles.

Also known as: Aliqopa

Endometrial Cancer (EC); Follicular Lymphoma (FL)

Ketogenic Diet OTHER

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.

Endometrial Cancer (EC); Follicular Lymphoma (FL)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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);

Sponsors & Collaborators

• Columbia University: lead
• Bayer: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Endometrial Neoplasms

Interventions

copanlisib; Diet, Ketogenic

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Results Point of Contact

• Title: Jennifer E. Amengual, MD
• Organization: Columbia University

jea2149@cumc.columbia.edu

212-326-5720

Study Officials

• Jennifer E. Amengual, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor of Medicine

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 11, 2021
• Study Start: February 10, 2022
• Primary Completion: June 9, 2023
• Study Completion: June 9, 2023
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)