Endometrial Cancer
Conditions
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
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.
Interventions
Sponsors
GOG Foundation
Faeth Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 2 years | Defined as the proportion of participants with measurable disease at baseline who have confirmed complete response (CR) or partial response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) at 6 months | Up to 5 years. | Defined as PFS rate at 6 months. |
| Overall survival (OS) | Up to 5 years. | Defined as the time from first dose to death. |
| Progression free survival (PFS) | Up to 5 years. | Defined as the time from first dose until the date of disease progression or death. |
| Duration of response (DoR) | Up to 5 years. | Defined for participants with confirmed CR or PR as the time from response until date of documented disease progression or death. |
| Safety and tolerability of drugs by assessment of adverse events (AEs) / serious adverse events (SAEs) | Up to 2 years. | Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V5.0). |
| Clinical benefit rate (CBR) | Up to 5 years. | Defined as the percentage of participants who achieve complete response (CR), partial response (PR), or have stable disease (SD) of at least 16 or 24 weeks. |
Countries
United States
Contacts
Primary ContactMedical Monitor
Outcome results
None listed