Clinical trial NCT06463028: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: Serabelisib
Sapanisertib
Paclitaxel
Taxol
Antineoplastic Agents
PI3K
AKT
mTOR
Dual PI3K/mTOR inhibition
Genetic mutation
Cisplatin
Carboplatin
Genital Diseases
Endometrial Neoplasms
Advanced Endometrial Carcinoma
Recurrent Endometrial Carcinoma
Metastatic Endometrial Carcinoma
Endometrial Cancer
Endometrioid Carcinoma
Cancer of Endometrium
Cancer of the Endometrium
Carcinoma of Endometrium
Endometrial Carcinoma
Endometrium Cancer
Neoplasms, Endometrial
Metabolism
Synthetic Lethality
Metabolism Programming
PIK3CA
PIK3CA Mutation
PI3K Gene Mutation
PI3K/AKT/mTOR Pathway Mutation
AKT Gene Mutation
mTOR Gene Mutation
Lead sponsor: Faeth Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: GOG Foundation
First posted: 2024-06-17
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 5 years.
measure: Progression free survival (PFS) at 6 months
timeFrame: Up to 5 years.
measure: Overall survival (OS)
timeFrame: Up to 5 years.
measure: Clinical benefit rate (CBR)
timeFrame: Up to 5 years.
measure: Duration of response (DoR)
timeFrame: Up to 5 years.
measure: Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs)
timeFrame: Up to 2 years.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists, North
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists, East
state: Florida
city: Brandywine
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Maple Grove
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Albany
country: United States
facility: Women's Cancer Care Associates, LLC
state: New York
city: Eugene
country: United States
facility: Oncology Associates of Oregon, P.C.
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Doylestown
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: The Woodlands
country: United States
facility: Texas Oncology - Gulf Coast
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, P.C.
state: Virginia
Study officials:
References:
citation: 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.