A Study of Alpelisib and Fulvestrant to Treat Endometrial Cancer

NCT05154487 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: GOG-3069
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 18

Brief 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.

Conditions

Endometroid Endometrial Cancer

Keywords

advanced; persistent; recurrent; PIK3CA-mutated; ER-postive

Outcome Measures

Primary Outcomes (1)

• Response rate

  To determine the objective response rate of the combination of alpelisib and fulvestrant in patients with advanced, persistent or recurrent PIK3CA-mutated ER-positive endometrioid endometrial cancer. Respnse criteria based on RECIST Version 1.1 (complete or partial response).

  Response to treatment is assessed by RECIST Version 1.1 criteria every 8 weeks with CT scan or MRI through completion of treatment (complete or partial response). Patients receive treatment until disease progression and are followed for 5 years.

Secondary Outcomes (1)

• Drug Toxicity (Side Effects)

  Side effects are monitor from the start of treatment to discontinuation of treatment assessed every 4 weeks. Patients are treated until disease progression and are followed for 5 years.

Study Arms (1)

Apelisib and Fulvestrant

EXPERIMENTAL

alpelisib 300mg orally daily of each 28-day cycle fulvestrant 500mg IM on Day 1 and Day 15 of Cycle 1, then 500mg IM on Day 1 of each 28-day cycle.

Drug: Alpelisib Pill; Drug: Fulvestrant injection

Interventions

Alpelisib Pill DRUG

Kinase inhibitor

Also known as: Piqray

Apelisib and Fulvestrant

Fulvestrant injection DRUG

estrogen receptor agonist

Also known as: Faslodex

Apelisib and Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• Prior hormone therapy (progesterone, tamoxifen, aromatase inhibitor) is allowed and not considered a prior line of therapy. Prior treatment with fulvestrant not allowed.
• There are no limits on the number of prior lines of chemotherapy. Patients who received prior chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade less than or equal to 1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 21 days is required between last chemotherapy dose and initiation of therapy.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and initiation of therapy.
• Patient must be able to swallow oral medications.
• Patient must have an ECOG performance status of 0 to 2.

You may not qualify if:

• Patients who have previously received fulvestrant or any PIK3CA, PI3K, mTOR, or AKT inhibitor.
• Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers, or uterine sarcomas.
• Patients with known intolerance or hypersensitivity to alpelisib or fulvestrant, or any of their excipients.
• Patient has had major surgery within 14 days prior to study treatment start and/or has not recovered from major side effects.
• Patients with history of osteonecrosis of the jaw.
• 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.
• 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.
• 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).
• Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction, unstable angina, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of clinically significant cardiac arrhythmias (i.e. ventricular tachycardia or ventricular fibrillation, complete left bundle branch block, high grade AV block (e.g. bifascicular block, Mobitz type II and third degree AV block without pacemaker in place) or serious cardiac arrhythmia requiring medication. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
• Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or Fridericia QT correction formula (QTcF) \> 470 msec at screening.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months prior to the first date of study therapy.

Sponsors & Collaborators

• GOG Foundation: lead
• Novartis: collaborator

Study Sites (18)

City of Hope

Duarte, California, 91010, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

AdventHealth Gynecologic Oncology

Orlando, Florida, 32804, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Moffit Cancer Center at International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Moffit Cancer Center at Wesley Chapel

Wesley Chapel, Florida, 33544, United States

Location

Ascension St. Vincent

Indianapolis, Indiana, 46260, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40241, United States

Location

Johns Hopkins Medicine

Baltimore, Maryland, 21287, United States

Location

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

Location

QCC- Northwell Health Physicians Partners Medical

Rego Park, New York, 11374, United States

Location

Kettering Health Cancer Center

Kettering, Ohio, 45429, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC

Tulsa, Oklahoma, 74146, United States

Location

Legacy Good Samaritan Medical Center

Portland, Oregon, 97210, United States

Location

Legacy Meridian Park Medical Center

Tualatin, Oregon, 97062, United States

Location

Legacy Salmon Creek Medical Center

Vancouver, Washington, 98686, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Recurrence

Interventions

Alpelisib; Fulvestrant

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Stephanie Gaillard, MD

  GOG Foundation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 13, 2021
• Study Start: September 11, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

US (18)