Phase II Study of ELacestrant in Combination With Abemaciclib or Elacestrant Alone In p53 Wild Type, Estrogen Receptor-positive Advanced or recurrenT Endometrial Cancer (ELITE)
The researchers are doing this study to find out whether elacestrant is an effective and safe treatment alone or in combination with abemaciclib for people with advanced or recurrent ER+ endometrial cancer.
• Age ≥18 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have received previous platinum-based chemotherapy and treatment with a PD-1 inhibitor, together or separately, prior to enrolling on this trial.
• Patients may have received no more than 1 prior line of chemotherapy for management of endometrial carcinoma. This includes platinum-based chemotherapy alone or combined with a PD-1 inhibitor, small molecule agents, and chemotherapy in combination with radiation therapy. A washout period of 14 days is required for chemotherapy
• °Adjuvant chemotherapy completed ≥ 12 months prior will not be counted toward prior therapy
• Patients may have received ≤ one prior line of endocrine therapy for management of endometrial carcinoma.
• No prior treatment with a CDK4/6 inhibitor
• Measurable disease per RECIST v 1.1 criteria
• °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 of tumor ≥ 90 days following completion of radiation therapy.
• Advanced or recurrent endometrial carcinoma that is refractory to curative therapy.
• Patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, de-differentiated, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma.
• Patient must have ER-positive tumor status either from the most recent sample of advanced/recurrent disease or from an archival tissue.
• °Documentation of ER-positive tumor with ≥ 1% staining by IHC as defined in the 2010 or 2020 American Society for Clinical Oncology recommendations for ER testing (Hammond 2010, Allison 2020)
• p53 wt by IHC or TP53 wt by next generation sequencing platform either from the most recent sample of advanced/recurrent disease or from an archival tissue.
• No known dMMR or POLE mutation
• If MSK IMPACT mutational profiling or mutational profiling performed in a CLIA laboratory is not already performed, must have tissue available for MSK IMPACT molecular profiling to be performed clinically
• Female patients may be either postmenopausal or premenopausal or perimenopausal. Postmenopausal status is defined by:
‣ Age ≥ 60 years
⁃ Age \< 60 years and amenorrhea for ≥12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) or a follicle-stimulating hormone value \>40 mIU/mL and an estradiol value \<40 pg/mL or in postmenopausal ranges per local reference ranges
⁃ Documentation of prior bilateral oophorectomy, at least 1 month before first dose of trial therapy.
⁃ Premenopausal or perimenopausal patients must be concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist for ovarian suppression starting at least 4 weeks before the start of trial therapy and continue LHRH agonist during the study.
• The effects of elacestrant and abemaciclib on the developing human fetus are unknown. For this reason and because SERDs and CDK4/6 inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) within 28 days of the first dose of study therapy, during study therapy, and for 120 days following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately
• °Highly effective and low user dependency, non-hormonal contraception methods include: i. Intrauterine device (non-hormonal). ii. Total abstinence iii. Bilateral tubal occlusion/ligation. iv. Have a vasectomized partner (sole sexual partner) with confirmed azoospermia
• Any prior radiotherapy directed at the malignant tumor must be discontinued prior to first study treatment. 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 the end of radiotherapy and randomization.
• Have adequate laboratory values as defined below:
• °Hematologic
• Absolute neutrophil count ≥1500/mm3 (≥1.5 × 10\^3/μL)
• Platelets ≥100,000/μL
• Hemoglobin ≥9.0 g/dL
• °Renal
• Creatinine clearance (CrCL) Creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula
• Urinalysis Urine protein \< 2+ (or 24 hour urine protein quantification \< 1.0 g)
• °Hepatic
• Total bilirubin ≤1.5 ×ULN (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
• AST and ALT ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• TSH TSH within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required.
• Coagulation Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy or due to prophylactic coagulation)
• Serum Albumin Serum albumin ≥3.0 g/dL (≥30 g/L)