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A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE2

A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer

Phase 2 Study of Alpelisib and Fulvestrant for PIK3CA-mutated Estrogen Receptor (ER)-Positive Endometrioid Endometrial Cancers

NCT05154487•GOG Foundation

View on ClinicalTrials.gov

Summary

This is a 2 stage multi-center study designed to evaluate the efficacy of the combination of alpelisib and fulvestrant in patients with PIK3CA-mutated ER-positive endometrioid endometrial cancers by estimating the objective response rate (ORR). Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.

Eligibility

Age

18 - No limit years

Sex

FEMALE

Healthy Volunteers

Inclusion Criteria

•1. Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy. Histologic confirmation of recurrent disease is required. For cases of persistent disease, histologic confirmation of the primary disease with radiologic evidence of progression is required.
•2. Patients must have endometrioid histology (all grades allowed) based on hysterectomy or biopsy specimen and have positive expression of ER and oncogenic PIK3CA mutation per criteria below.
•a. PIK3CA mutations considered oncogenic or likely oncogenic. i. Oncogenic/likely oncogenic PIK3CA mutations identified on tests performed by the labs listed on https://ecog-acrin.org/nci-match-eay131-designated-labs will be considered confirmed for the purposes of this study.
•ii. Oncogenic/likely oncogenic PIK3CA mutations identified by other tests will need to be confirmed by the study prior to enrollment.
•b. Estrogen receptor (ER) status will be considered positive if ≥1% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. Pathology report documenting ER status must be provided at enrollment.
•Sites are required to report results of previous MMR and/or MSI status testing in the EDC if available.
•3. All patients must have measurable disease. Measurable disease is defined by RECIST version 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured by CT or MRI.
•Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
•4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III or metastatic/recurrent/Stage IV is permitted. Prior chemoradiotherapy for a pelvic recurrence is permitted.
•Prior immunotherapy and/or targeted therapy is allowed in addition to, in combination with, in lieu of, or subsequent to prior chemotherapy.
+31 more criteria

Exclusion Criteria

•1. Patients who have previously received fulvestrant or any PIK3CA, PI3K, mTOR, or AKT inhibitor.
•2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers, or uterine sarcomas.
•3. Patients with known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their excipients.
•4. Patient has had major surgery within 14 days prior to study treatment start and/or has not recovered from major side effects.
•5. Patients with an established diagnosis of diabetes mellitus type I or uncontrolled type II (based on fasting blood glucose \[FBG\] and HemoglobinA1c \[HbA1c\], see inclusion criterion 67).
•6. Patients with history of osteonecrosis of the jaw.
•7. Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol.
•8. Patients with active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection (such as known human immunodeficiency virus (HIV) positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]). Screening is not required for enrollment.
•9. Patients with a serious pre-existing medical condition(s) that would preclude participation in this study (for example: interstitial lung disease or pneumonitis, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e. estimated creatinine clearance \<30ml/min), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea).
•10. Patients with a known history of cardiac disease. This includes:
+21 more criteria

Locations (18)

City of Hope

Duarte, California, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

AdventHealth Gynecologic Oncology

Orlando, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Moffit Cancer Center at International Plaza

Tampa, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Moffit Cancer Center at Wesley Chapel

Wesley Chapel, Florida, United States

Ascension St. Vincent

Indianapolis, Indiana, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Johns Hopkins Medicine

Baltimore, Maryland, United States

Key Dates

Start Date

September 11, 2024

Primary Completion Date

May 1, 2028

Completion Date

November 1, 2028

Last Updated

March 3, 2026

Enrollment

ESTIMATED participants

Conditions

Endometroid Endometrial Cancer

Interventions

Alpelisib Pill

DRUG

Fulvestrant injection

DRUG