Clinical Trials /

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

NCT03056833

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ribociclib (Ribociclib (LEE-011)) With Platinum-based Chemotherapy in Recurrent Platinum Sensitive Ovarian Cancer
  • Official Title: Phase I Trial of Ribociclib (Ribociclib (LEE-011)) With Platinum-based Chemotherapy in Recurrent Platinum Sensitive Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-006
  • SECONDARY ID: CLEE011XUS28T
  • NCT ID: NCT03056833

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Carcinoma

Interventions

DrugSynonymsArms
ribociclibRibociclib
PaclitaxelRibociclib
CarboplatinRibociclib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
RibociclibExperimentalRibociclib (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.
  • ribociclib
  • Paclitaxel
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Must have had at least 1 prior line of platinum-based therapy

          3. ECOG 0-1 with life expectancy of ≥ 3 months

          4. 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

          5. 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

          6. Must be able to swallow ribociclib (LEE-011) tablet/capsule

          7. Documented disease recurrence/progression based on GCIG-RECIST

          8. Able to provide informed consent and comply with all study protocols

          9. 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.

         10. Women of child-bearing potential (those who have had a menstrual cycle within the last
             year and have not had a tubal ligation or surgical removal of both ovaries and/or
             hysterectomy) must agree to abstain from vaginal intercourse or use and continue
             highly effective methods of contraception for 3 weeks after discontinuation of study
             treatment.

         11. Patients must have histologically confirmed malignancy that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective.

        Exclusion Criteria:

          1. Borderline or low-malignant potential histology.

          2. Platinum-resistant disease (as defined as progressive disease within 6 months of
             completion of chemotherapy with a platinum agent)

          3. Grade 3 baseline neuropathy.

          4. Known hypersensitivity to any of the excipients of ribociclib (LEE-011), including
             peanuts and soy

          5. Prior use of CDK4/6 inhibitors.

          6. Congenital long QT syndrome or family history of unexpected sudden cardiac death

          7. 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).

          8. Impairment of gastrointestinal (GI) function or disease that may significantly alter
             the absorption of the study drugs

          9. History of HIV infection

         10. 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.).

         11. 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

         12. Use of prohibited medications (see section 5.3) that cannot be changed to an
             alternative therapy

         13. 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.

             a. The following uses of corticosteroids are permitted: single doses, topical
             applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
             diseases), eye drops or local injections (e.g., intra-articular)

         14. Patient is 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.

         15. Use of herbal supplements unless discontinued ≥7 days prior to initiation of study
             drug

         16. Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to be
             discontinued 7 days prior to initiation of study drug

         17. Pregnancy or lactation

         18. Participation in a prior investigational study within 30 days prior to enrollment or
             within 5 half-lives of the investigational product, whichever is longer

         19. Patient who 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 ≥25% of the bone marrow (Ellis, 1961) was irradiated.

         20. Patient 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).

         21. Patient has not recovered from all toxicities related to prior anticancer therapies to
             NCI-CTCAE version 5 Grade ≤1 (Exception to this criterion: patients with any grade of
             alopecia and/or neuropathy ≤ grade 2 are allowed to enter the study).

         22. Patient with a Child-Pugh score B or C.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximal tolerated dose (MTD) of ribociclib (LEE-011) when given with carboplatin + paclitaxel in platinum-sensitive recurrent ovarian cancer
Time Frame:56 days
Safety Issue:
Description:Participants will be observed for the first two treatment cycles (2, 28 day cycles) and maximum tolerated dose will be determined.

Secondary Outcome Measures

Measure:Number of participants that respond to treatment
Time Frame:18 months post treatment
Safety Issue:
Description:Overall response rate (ORR) will be analyzed. The number of patients that respond to treatment (exhibit Partial Response (PR) or Complete Response (CR)) will be recorded. PR is defined as at least a 50% reduction in CA 125 levels (response must be confirmed and maintained for at least 28 days) and/or at least 30% decrease in the sum diameters of target lesions. CR is defined as normalization of CA125 levels ((response must be confirmed and maintained for at least 28 days) and disappearance of all target lesions.
Measure:Time from treatment until disease progression or death
Time Frame:18 months post treatment
Safety Issue:
Description:Progression is defined as one of the following: Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart or Patients with elevated CA-125 before treatment, which never normalizes, must show evidence of CA-125 greater than, or equal to, 2 times the nadir value on 2 occasions at least 1 week apart or Patients with CA-125 in the reference range before treatment must show evidence of CA-125 greater than, or equal to, 2 times the upper limit of the reference range on 2 occasions at least 1 week apart Increase in at least 20% in sum of diameters of target lesions or any new lesions or unequivocal increase in non-target lesions. Response determined via measurable disease (measurement of target and non-target lesions) takes precedence over CA125 criteria Stable Disease (SD): CA
Measure:Number of participants encountering toxicity at each dose level
Time Frame:30 days post treatment
Safety Issue:
Description:Patients will potentially be treated with 3 different dose levels of ribociclib in combination with platinum-based chemotherapy.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ronald Buckanovich

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