Combination of Serabelisib and Insulin Suppressing Diet With or Without Nab-paclitaxel in Subjects With Advanced Solid Tumors With PIK3CA Mutations

NCT05300048 | Terminated Phase 1 FDA Drug

• 1 other identifier: SER-ISD1-001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 17

Brief Summary

This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib (an investigational PI3K inhibitor) when combined with an ISD and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

Conditions

Advanced Solid Tumor; PIK3CA Mutation; PTEN Loss of Function Mutation

Keywords

PIK3CA Mutation; PTEN Loss of Function Mutation

Outcome Measures

Primary Outcomes (6)

• Cohorts 1a/1b: Evaluate safety

  Incidence of related AEs

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Evaluate compliance

  Compliance of Study intervention

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring Cmax.

  Standard pharmacokinetic parameters (Cmax)

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring Tmax.

  Standard pharmacokinetic parameters (Tmax).

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Evaluate the pharmacokinetic impact by measuring AUC.

  Standard pharmacokinetic parameters (AUC).

  Through study completion, up to 12 months.

• Cohorts 2, 3, 4: Use the Objective Response Rate (ORR) to assess the antitumor efficacy of serabelisib in combination with a Study ISD.

  Proportion of subjects who have best overall response of either complete response (CR) or partial response (PR)

  Through study completion, an average of 8 months.

Secondary Outcomes (15)

• Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring ORR.

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring PFS.

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring OS.

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring DoR.

  Through study completion, up to 12 months.

• Cohorts 1a/1b: Antitumor efficacy of study intervention by measuring DCR.

  Through study completion, up to 12 months.

Other Outcomes (7)

• Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention.

  Through study completion, up to 12 months.

• Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention.

  Through study completion, up to 12 months.

• Cohorts 1a/1b, 2, 3, 4: Assessment of PD of study intervention.

  Through study completion, up to 12 months.

Study Arms (5)

Cohort 1a - Dose Modification without nab-paclitaxel

EXPERIMENTAL

Subjects with any solid tumor will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months

Drug: Serabelisib; Other: Insulin Suppressing Diet

Cohort 1b - Dose Modification with Nab-Paclitaxel

EXPERIMENTAL

Subjects with endometrial cancer, ovarian clear cell or ovarian endometriod carcinoma will receive multiple doses of serabelisib administered orally and will consume Insulin Suppressing Diet for up to 12 months. In addition, these subjects will receive nab-paclitaxel intravenously weekly.

Drug: Serabelisib; Other: Insulin Suppressing Diet; Drug: Nab paclitaxel

Cohort 2 - Expansion Colorectal Cancer

EXPERIMENTAL

Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months

Drug: Serabelisib; Other: Insulin Suppressing Diet

Cohort 3 - Expansion Endometrial Cancer

EXPERIMENTAL

Subjects will receive dose of serabelisib as determined from Cohort 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.

Drug: Serabelisib; Other: Insulin Suppressing Diet; Drug: Nab paclitaxel

Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma

EXPERIMENTAL

Subjects will receive dose of serabelisib as determined from Cohorts 1a and 1b, and will consume Insulin Suppressing Diet for up to 12 months. If results from Cohort 1b show a favorable risk-benefit ratio, nab-paclitaxel will be administered intravenously weekly.

Drug: Serabelisib; Other: Insulin Suppressing Diet; Drug: Nab paclitaxel

Interventions

Serabelisib DRUG

serabelisib administered orally

Cohort 1a - Dose Modification without nab-paclitaxel; Cohort 1b - Dose Modification with Nab-Paclitaxel; Cohort 2 - Expansion Colorectal Cancer; Cohort 3 - Expansion Endometrial Cancer; Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma

Insulin Suppressing Diet OTHER

3 meals consumed daily (i.e., breakfast, lunch, dinner) and optional snacks provided dependent on caloric needs

Cohort 1a - Dose Modification without nab-paclitaxel; Cohort 1b - Dose Modification with Nab-Paclitaxel; Cohort 2 - Expansion Colorectal Cancer; Cohort 3 - Expansion Endometrial Cancer; Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma

Nab paclitaxel DRUG

nab-paclitaxel administered intravenously weekly

Cohort 1b - Dose Modification with Nab-Paclitaxel; Cohort 3 - Expansion Endometrial Cancer; Cohort 4 - Expansion Ovarian Clear Cell or Ovarian Endometrioid Carcinoma

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent.
• Age ≥18 at Visit -1 (screening).
• Histologically or cytologically confirmed recurrent solid tumors.
• Cohort 1a: any extracranial solid tumor (may include EC, ovarian clear cell, or ovarian endometrioid carcinoma if subject is not eligible for nab-paclitaxel in Cohort
• Cohort 1b: either recurrent or persistent endometrial adenocarcinoma (EC) with the following histologic epithelial cell types: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, transitional cell carcinoma, and carcinosarcoma or; ovarian cancer (OC) with the primary tumor having ≥ 50% clear cell histomorphology or ovarian clear cell or ovarian endometrioid carcinoma.
• Cohort 2: adenocarcinoma of the colon or rectum.
• Cohort 3: recurrent or persistent endometrial adenocarcinoma with the following histologic epithelial cell types as described for Cohort 1b
• Cohort 4: OC primary tumor carcinomas as described for Cohort 1b
• Tumor must harbor an activating mutation in the PIK3CA gene with or without PTEN loss, either previously documented or determined during screening.
• Fresh or archival tumor biopsy with sufficient material to be sent to the designated laboratory for PD analyses. For subjects who consent to future research, an additional 5 slides from a surgical specimen or biopsy is required.
• Cohort 1a - Dose Modification (subjects with any solid tumor): failed, were intolerant of, or ineligible for no more than three prior lines of therapy (LOT) for advanced/metastatic disease or refused SOC therapy.
• For all cohorts, in the unlikely scenario that a subject refused all available SOC they may proceed with trial. These subjects would be regarded as having 0 prior LOT.
• Cohorts 1b, 2, 3, and 4 - failed, were intolerant of, ineligible for, or have refused SOC therapy for advanced/metastatic disease (AJCC stage III and IV) and:
• Cohort 2 (subjects with colorectal cancer): Have failed no more than two prior LOT for metastatic CRC.
• Cohort 1b, and Cohort 3 (subjects with EC): Have no more than three prior chemotherapeutic regimens for management of endometrial carcinoma (neo-adjuvant and/or adjuvant chemotherapy will be counted as one prior LOT). Prior hormonal therapy will not count as a systemic regimen.

You may not qualify if:

• Diagnosis of primary malignant brain tumor.
• Has had serabelisib, alpelisib, or other PI3K inhibitor.
• Leptomeningeal disease and symptomatic or untreated brain metastases.
• Diagnosis of, or requiring treatment for, another malignancy within the past 2 years (excluding a history of carcinoma in situ of the cervix, superficial non-melanoma skin cancer, or superficial bladder cancer that has been adequately treated, or stage 1 prostate cancer that does not require treatment or requires only treatment with luteinizing hormone-releasing hormone agonists or antagonists if initiated at least 90 days prior to the first dose of Study Drug).
• Is less than 21 days from therapeutic radiation or chemotherapy prior to the first day of dosing with Study Drug and has not recovered to Grade ≤ 1 from all clinically significant toxicities related to prior therapies.
• For subjects receiving nitrosoureas or mitomycin C, the subject is \< 6 weeks from last dose. For monoclonal antibody therapy, the subject is \< 1 half-life or \<4 weeks from the last dose.
• Chronic, systemically administered glucocorticoids in doses equivalent to \>5 mg prednisone daily. Replacement corticosteroids for adrenal insufficiency are permitted.
• Diabetes mellitus requiring insulin or insulin secretagogue therapy.
• Poorly controlled diabetes mellitus defined as glycosylated hemoglobin A1c (HbA1c) \>7.5% or fasting blood sugar \>160 mg/ dL.
• Known impaired cardiac function or clinically significant cardiac disease.
• QTcF interval \>470 msec found at screening.
• Myocardial infarction, cardiac stent placement, or unstable angina within 6 months before the first administration of Study Drug.
• Have clinically significant peripheral vascular disease.
• Manifestations of malabsorption
• Other clinically significant comorbidities.

Sponsors & Collaborators

• Faeth Therapeutics: lead

Study Sites (17)

University of Alabama

Birmingham, Alabama, 35429, United States

Location

Pacific Cancer Specialists

Anaheim, California, 92801, United States

Location

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Community Health Network, Inc.

Indianapolis, Indiana, 46250, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55902, United States

Location

New Jersey Cancer Care, PA

Belleville, New Jersey, 07109, United States

Location

Englewood Health

Englewood, New Jersey, 07631, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

East Carolina University

Greenville, North Carolina, 27858, United States

Location

University of Pennsylvania Health System, Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Baptist Hospitals of Southeast Texas

Beaumont, Texas, 77701, United States

Location

Oncology Consultants, PA

Houston, Texas, 77030, United States

Location

Lumi Research

Kingwood, Texas, 77339, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Interventions

serabelisib; Taxes

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Officials

• Vicky Makker

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2022
• First Posted: March 29, 2022
• Study Start: April 22, 2022
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)