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

Stopped early · Phase 1

Conditions studied: Advanced Solid Tumor, PIK3CA Mutation, PTEN Loss of Function Mutation

In brief

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.

Key facts

Study ID

NCT05300048

Run by

Faeth Therapeutics

People needed

34

Starts

2022-04-22

Expected to finish

2025-04-30

Last updated by the study team

2026-04-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• 1b)
• 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.
• Cohort 1b, and Cohort 4 (subjects with clear cell or endometrioid OC): Subjects must have had no more than three prior chemotherapeutic regimens for management of ovarian carcinoma. Prior hormonal therapy will not count as a systemic regimen.
• Life expectancy of at least 3 months.
• At least one measurable lesion (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
• ECOG PS of 0 to 1.
• Adequate organ function
• Absolute neutrophil count (ANC) ≥1.0 × 10\^9/L or ≥1.5 x 10\^9/L if planned to be treated with nab-paclitaxel, platelet count ≥75 × 10\^9/L, and hemoglobin ≥8.5 gm/dL (may be transfused to reach this hemoglobin level unless due to blood loss).
• Liver transaminases (AST and ALT) ≤2.5 × upper limit of normal (ULN) (<5 × ULN if liver metastases are present), and total bilirubin ≤1.5 × ULN (<3 x ULN if subject has Gilbert Syndrome).
• INR ≤1.5 x ULN unless subject is on anticoagulants that would affect the INR, then INR must be in the desired therapeutic range as judged by the Investigator.
• Albumin level ≥3.0 mg/dL or ≥ the lower limit of normal.

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.
• Pregnant (positive serum pregnancy test), planning to become pregnant during the study, or breastfeeding/planning to breastfeed during the study.
• Have taken strong CYP3A4 inducers/inhibitors within 7 days before the first administration of serabelisib or have conditions that require the concomitant use of CYP3A4 inducers/inhibitors.
• Untreated or poorly controlled, gastro-esophageal reflux disease.
• Have taken histamine-H2 receptor antagonists within 12 hours before the first administration of serabelisib.
• Have taken PPI within 7 days or 5 half-lives (whichever is the shorter duration) before the first administration of serabelisib or are anticipated to need PPI during the study.
• Have taken neutralizing antacids within 4 hours before the first administration of serabelisib or are anticipated to need frequent antacid use during the study.
• Subjects with poorly controlled human immunodeficiency virus, hepatitis B virus, and/or hepatitis C virus infections.
• Known allergies to nab-paclitaxel or excipients, serabelisib or excipients or the ISD
• Severe, uncontrolled gout.
• A BMI <18.5 kg/m2, or serious or refractive cachexia or anorexia that, in the Investigator's opinion, realistically prohibits subjects from having energy or appetite sufficient to reliably engage in a strict ISD regimen for an extended time.

Where it is running

• University of Alabama — Birmingham, Alabama, United States
• Pacific Cancer Specialists — Anaheim, California, United States
• Valkyrie Clinical Trials — Los Angeles, California, United States
• Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States
• Community Health Network, Inc. — Indianapolis, Indiana, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• New Jersey Cancer Care, PA — Belleville, New Jersey, United States
• Englewood Health — Englewood, New Jersey, United States
• Northwell Health — Lake Success, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• East Carolina University — Greenville, North Carolina, United States
• University of Pennsylvania Health System, Perelman Center for Advanced Medicine — Philadelphia, Pennsylvania, United States
• Avera Cancer Institute — Sioux Falls, South Dakota, United States
• Baptist Hospitals of Southeast Texas — Beaumont, Texas, United States
• Oncology Consultants, PA — Houston, Texas, United States
• Lumi Research — Kingwood, Texas, United States
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States

Full record on ClinicalTrials.gov

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