Ribociclib (Ribociclib (LEE-011)) With Platinum-based Chemotherapy in Recurrent Platinum Sensitive Ovarian Cancer

NCT03056833 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 18-006CLEE011XUS28T
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 8

Brief Summary

Investigators hypothesize that concurrent ribociclib treatment and chemotherapy will enhance the response to platinum-based therapy and maintenance therapy will slow ovarian cancer tumor growth leading to prolongation in progression free survival.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose (MTD) of ribociclib (LEE-011) when given with carboplatin + paclitaxel in platinum-sensitive recurrent ovarian cancer

  Participants will be observed for the first two treatment cycles (2, 28 day cycles) and maximum tolerated dose will be determined.

  56 days

Secondary Outcomes (4)

• Number of participants that respond to treatment

  18 months post treatment

• Time from treatment until disease progression or death

  18 months post treatment

• Number of participants encountering toxicity at each dose level

  30 days post treatment

• Overall Survival (OS)

  Up to 5 years

Study Arms (1)

Ribociclib

EXPERIMENTAL

Ribociclib (LEE-011) will be used as concurrent therapy with platinum-based chemotherapy in platinum-sensitive recurrent ovarian cancer. Participants will receive 200, 400, or 600mg of ribociclib per day in combination with carboplatin + paclitaxel. Subjects will receive 6 cycles of carboplatin + paclitaxel given weekly with ribociclib.

Drug: ribociclib; Drug: Paclitaxel; Drug: Carboplatin

Interventions

ribociclib DRUG

Ribociclib (LEE-011) will be given on days 1-4, 8-11, and 15-18 of a 28 day cycle at 200, 400, or 600mg/day during the dose escalation phase. During the maintenance phase, ribociclib (LEE-011) will be given at 600mg/day, 3 weeks on, 1 week off until progression.

Ribociclib

Paclitaxel DRUG

During the escalation phase Paclitaxel will be given on days 1, 8, and 15 of a 28 day cycle.

Ribociclib

Carboplatin DRUG

During the escalation phase Carboplatin will be given on days 1, 8, and 15 of a 28 day cycle.

Ribociclib

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women ≥18 years old
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥18 years old with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer (defined as recurrent disease \>6 months after completing last platinum-based chemotherapy) eligible to receive platinum-based doublet chemotherapy.
• Must have had at least 1 prior line of platinum-based therapy
• ECOG 0-1 with life expectancy of ≥ 3 months
• Adequate organ function:
• Serum creatinine ≤1.5mg/dL or 24-hour clearance ≥50 mL/min
• AST/ALT \<2.5x ULN (or \<5x ULN if liver metastasis are present)
• Total bilirubin ≤ULN or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
• Hemoglobin ≥9 gm/dl, Platelets ≥100,000/µL, ANC ≥1500/µL
• INR ≤1.5
• Potassium, total calcium (corrected for serum albumin), magnesium, and sodium within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
• Screening ECG (defined as the mean of the triplicate ECGs) with QTcF interval at screening ≤450msec (using Fridericia's correction) and resting heart rate 50-90bpm
• Must be able to swallow ribociclib (LEE-011) tablet/capsule
• Documented disease recurrence/progression based on GCIG-RECIST
• Able to provide informed consent and comply with all study protocols
• Treated CNS metastasis allowed if treatment is complete ≥8 weeks prior to enrollment. Patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after completion of radiation therapy. CNS disease must be stable or regressed on repeat imaging performed at least 4 weeks after completion of therapy.

You may not qualify if:

• Borderline or low-malignant potential histology.
• Platinum-resistant disease (as defined as progressive disease within 6 months of completion of chemotherapy with a platinum agent)
• Grade 3 baseline neuropathy.
• Known hypersensitivity to any of the excipients of ribociclib (LEE-011), including peanuts and soy
• Prior use of CDK4/6 inhibitors.
• Congenital long QT syndrome or family history of unexpected sudden cardiac death
• 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 or per physician discretion that the previous cancer was adequately treated with curative intent and unlikely to recur (the study PI must concur with this determination).
• Impairment of gastrointestinal (GI) function or disease that may significantly alter the absorption of the study drugs
• History of HIV infection
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks and contraindicate patient's 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, including any of the following:
• a. Heart Association functional classification III-IV) b. Documented cardiomyopathy c. Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening d. Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) e. Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: i. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• ii. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication iii. Inability to determine the QT interval on screening (QTcF using Fridericia's correction) f. Systolic blood pressure (SBP) \>160 mmHg or \<90 mmHg at screening g. History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• Use of prohibited medications (see section 5.3) that cannot be changed to an alternative therapy
• Patient is 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.

Sponsors & Collaborators

• Ronald Buckanovich: lead

Study Sites (8)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

UPMC Hillman Cancer Center Upper St. Clair

Bethel Park, Pennsylvania, 15102, United States

Location

UPMC Hillman Cancer Center Arnold Palmer at Mountain View

Greensburg, Pennsylvania, 15601, United States

Location

UPMC Hillman Cancer Center Arnold Palmer Medical at Norwin

Irwin, Pennsylvania, 15642, United States

Location

UPMC Hillman Cancer Center Arnold Palmer at Mt Pleasant

Mount Pleasant, Pennsylvania, 15666, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Hillman Cancer Center Passavant (OHA)

Pittsburgh, Pennsylvania, 15237, United States

Location

UPMC Hillman Cancer Center Washington

Washington, Pennsylvania, 15301, United States

Location

Related Publications (1)

• Coffman LG, Orellana TJ, Liu T, Frisbie LG, Normolle D, Griffith K, Uppal S, McLean K, Berger J, Boisen M, Courtney-Brooks M, Edwards RP, Lesnock J, Mahdi H, Olawaiye A, Sukumvanich P, Taylor SE, Buckanovich R. Phase I trial of ribociclib with platinum chemotherapy in ovarian cancer. JCI Insight. 2022 Sep 22;7(18):e160573. doi: 10.1172/jci.insight.160573.

  PMID: 35972817 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

ribociclib; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Lan G Coffman, M.D.

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 17, 2017
• Study Start: June 10, 2017
• Primary Completion: June 1, 2020
• Study Completion: August 1, 2022
• Last Updated: September 7, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)