Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel and a Substudy With an Insulin-Suppressing Diet in Patients With Advanced/Recurrent Endometrial Cancer

Official title

An Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel, and a Substudy Evaluating PIKTOR With Paclitaxel Plus an Insulin-Suppressing Diet, in Patients With Advanced or Recurrent Endometrial Cancer

Overview

This is a Phase 2, multicenter, open-label, single-arm study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel in participants with advanced or recurrent endometrial cancer.

Detailed description

This is a Phase 2, multicenter, open-label, single-arm study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel in participants with advanced or recurrent endometrial cancer who have failed prior systemic therapies, including a platinum-based therapy and an immune checkpoint inhibitor, either separately or together.

Interventions

• Drug Sapanisertib
  Oral
• Drug Serabelisib
  Oral
• Drug Paclitaxel
  Infusion

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: Up to 2 years]

Secondary outcome measures (6)

• Progression free survival (PFS) [Time frame: Up to 5 years.]
• Progression free survival (PFS) at 6 months [Time frame: Up to 5 years.]
• Overall survival (OS) [Time frame: Up to 5 years.]
• Clinical benefit rate (CBR) [Time frame: Up to 5 years.]
• Duration of response (DoR) [Time frame: Up to 5 years.]
• Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs) [Time frame: Up to 2 years.]

Eligibility criteria

Inclusion criteria

• Histologically confirmed diagnosis of endometrioid endometrial carcinoma.
• Documented evidence of advanced or recurrent endometrial cancer that is not amenable to surgery/radiation for curative intent.
• Participant has received at least 1 but not more than 4 prior systemic therapies. Prior therapy must include platinum-based chemotherapy and a checkpoint inhibitor, either separately or in combination. If a subject has been unable to be treated with checkpoint inhibitor in the past due to medical contraindications, consult with Medical Monitor.
• PI3K/AKT/mTOR pathway gene alteration identified.
• At least 1 measurable target lesion according to RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at Screening.
• Non-pregnant, non-lactating females who are postmenopausal, surgically sterile or who agree to use effective contraceptive methods..

Exclusion criteria

• Participants with central nervous system metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study
• Active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas \[e.g., breast, cervix, bladder\], or basal or squamous cell carcinoma of the skin) within the past 24 months prior to treatment. Fully resected localized malignancies are eligible.
• Gastric feeding tube (gastrostomy tube), gastrointestinal malabsorption, gastrointestinal anastomosis, bowel obstruction, or any other condition that might affect the absorption of study treatment.
• Clinically significant (per Investigator judgement) hemoptysis or tumor bleeding.
• Significant cardiovascular impairment.
• Active, uncontrolled (requiring systemic antimicrobial therapy) infection.
• Concurrent participation in another therapeutic clinical trial.
• Prior radiation therapy within 21 days prior to start of study treatment.
• Strong CYP3A4 inhibitors and inducers are prohibited during the study. Strong CYP1A2 inhibitors as well as CYP1A2 inducers should be administered with caution and at the discretion of the Investigator. Alternative treatments, if available, should be considered. Additionally, strong CYP3A4 inhibitors or inducers should not be taken within 7 days before the first dose of study intervention.
• Participants who require PPIs or chronic use of antacids, histamine H2 receptor blockers, or other treatments to raise gastric pH.
• Prolongation of QTc interval to >480 ms.
• HbA1c ≥ 8.0% or fasting serum glucose > 160 mg/dL or fasting triglycerides > 300 mg/dL or receiving treatment with insulin.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 18 centers

• UC San Diego Moores Cancer Center — La Jolla
• University of California, San Francisco (UCSF) — San Francisco
• Mount Sinai Comprehensive Cancer Center — Miami Beach
• Florida Cancer Specialists, North — St. Petersburg
• Florida Cancer Specialists, East — West Palm Beach
• Maryland Oncology Hematology, P.A. — Brandywine
• Minnesota Oncology Hematology, P.A. — Maple Grove
• Women's Cancer Care Associates, LLC — Albany
• … and 10 more centers

Publications

• Starks DC, Rojas-Espaillat L, Meissner T, Williams CB. Phase I dose escalation study of dual PI3K/mTOR inhibition by Sapanisertib and Serabelisib in combination with paclitaxel in patients with advanced solid tumors. Gynecol Oncol. 2022 Sep;166(3):403-409. doi: 10.1016/j.ygyno.2022.07.005. Epub 2022 Jul 15. PMID 35843739

Identifiers

NCT: NCT06463028 · FTH-PIK-201 · GOG-3111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗