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Clinical Trial 20336

Cancer Type: Gynecological Tumor
Study Type: Treatment
NCT#: NCT03673124

Phase: Phase II
Prinicipal Investigator:

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Overview

Study Title

A Phase II Trial of Ribociclib (LEE011) plus Letrozole in Women with Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube or Peritoneum

Summary

The study evaluates the response to treatment with Ribociclib and Letrozole in patients with low grade serous cancer of the ovary, fallopian tube or peritoneum.

Objective

Primary Objective: To determine the response rate of patients receiving the combination of letrozole + Ribociclib. Secondary Objectives: To determine the clinical benefit (CR, PR, and SD) rate of patients receiving the combination of letrozole + Ribociclib. To determine the nature, frequency, and maximum degree of toxicity associated with this combination using CTCAE v5.0. To determine the progression-free survival of women receiving the combination of letrozole + Ribociclib. To determine the overall survival of women receiving the combination of letrozole + Ribociclib. Exploratory Objectives: To determine the expression of estrogen receptor (ER), progesterone receptor (PR), and proliferative index (ki-67) and their correlation with response and clinical benefit. To determine genomic signatures associated with response and clinical benefit of the combination of letrozole + Ribociclib.

Treatments

Therapies

Medications

Femara (Letrozole); LEE011 (Ribociclib); Letrozole (); Ribociclib ()

Inclusion Criteria

  • Patient has signed the Informed Consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements.
  • 18 years of age or older at time of study entry.
  • Willingness and ability to comply with study and follow-up procedures.
  • Histological confirmation of diagnosis of low-grade serous carcinoma of ovary, fallopian tube or peritoneum; Original diagnosis of de novo low-grade serous carcinoma or Original diagnosis of serous borderline tumor with subsequent diagnosis of low-grade serous carcinoma.
  • In order to prevent inclusion of patients with high-grade serous carcinoma, diagnosis of low-grade serous carcinoma will be verified as part of screening review by a gynecologic pathologist. Tissue for confirmation can be from primary tumor or recurrence.
  • Patient must have recurrent, measurable disease by RECIST v1.1.
  • There are no restrictions on number of prior therapies.
  • Patient cannot have previously received a prior cyclin dependent kinase inhibitor (CDKi). Patients who were treated with letrozole or another aromatase inhibitor for other indications must have not taken the drug for 6 months prior to initiating letrozole for this trial and may not have progressed on treatment.
  • Patients must not have remaining ovarian function to be included. In women who have at least one retained ovary, menopause must be confirmed with laboratory confirmation. Women who have ovarian function are eligible but must be placed on hormonal suppression. Menopause must be confirmed with laboratory confirmation, to include an estradiol level as this is assessed within 8 weeks of patient having been on tamoxifen.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade less than or equal to 1. 1. Patients with grade 1 taxane-induced neuropathy, any grade alopecia, amenorrhea, or other toxicities not considered a safety risk for the patient as per investigator's discretion are eligible. 1. Patient has adequate bone marrow and organ function as defined per protocol.
  • Patient with available standard 12-lead ECG with the following parameters at screening: QTcF interval at screening less than 450msec (using Fridericia's correction), Resting heart rate 50-90bpm
  • Must be able to swallow ribociclib and letrozole capsules/tablets.
  • Patients receiving tamoxifen or toremifine must have washout period of 5 half-lives prior to randomization.

  • Exclusion Criteria

    EXCLUSION CRITIERIA:

  • Known hypersensitivity to any of the excipients of ribociclib or letrozole.
  • Concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. Patients with known brain metastases are excluded.
  • Central Nervous System (CNS) involvement unless they meet ALL of the following criteria: At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment, Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Known history of HIV infection (testing not mandatory).
  • Any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, as further defined in protocol.
  • Currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug: Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges. That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5. Herbal preparations/medications, dietary supplements.
  • Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational product (whichever is longer) or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of Novartis study medical lead is required to establish eligibility.
  • Currently receiving warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed. Direct-Acting Oral Anticoagulants (DOACS) are permitted.
  • Currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment. The following uses of corticosteroids are permitted: a short duration (,5 days) of systemic corticosteriods; any durations of topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
  • Has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom greater than or equal to 25% of the bone marrow (Ellis, 1961) was irradiated.
  • Has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
  • A Child-Pugh score B or C.
  • Pregnant or breastfeeding patients
  • Women of child bearing potential unless they are using highly effective methods of contraception
  • Other exclusions apply

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