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Ovarian CancerPhase 1NCT03056833

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

A Phase 1 study testing ribociclib, Paclitaxel and Carboplatin in people with Ovarian Cancer and Fallopian Tube Cancer, run by Ronald Buckanovich at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
ribociclib, Paclitaxel and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
8 sitesUnited States
Study dates
10 Jun 2017to 1 Aug 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • 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.
  • 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.

Who cannot join

  • 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
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  • 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:
  • 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.
  • 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.
  • 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)
  • 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.
  • Use of herbal supplements unless discontinued ≥7 days prior to initiation of study drug
  • Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to be discontinued 7 days prior to initiation of study drug
  • Pregnancy or lactation
  • Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
  • 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.
  • 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).
  • 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).
  • Patient with a Child-Pugh score B or C.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • UPMC Hillman Cancer Center Upper St. Clair

    Bethel Park, Pennsylvania, 15102

  • UPMC Hillman Cancer Center Arnold Palmer at Mountain View

    Greensburg, Pennsylvania, 15601

  • UPMC Hillman Cancer Center Arnold Palmer Medical at Norwin

    Irwin, Pennsylvania, 15642

  • UPMC Hillman Cancer Center Arnold Palmer at Mt Pleasant

    Mount Pleasant, Pennsylvania, 15666

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • UPMC Hillman Cancer Center Passavant (OHA)

    Pittsburgh, Pennsylvania, 15237

  • UPMC Hillman Cancer Center Washington

    Washington, Pennsylvania, 15301

Other trials in United States

About this study

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

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.

Being tested
ribociclib, Paclitaxel, Carboplatin
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ribociclibDrug

    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.

  • PaclitaxelDrug

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

  • CarboplatinDrug

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

Study groups in NCT03056833
Study groupRoleWhat they receive
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.
Receives: Drug: ribociclib; Drug: Paclitaxel; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 56 days

Secondary outcomes (4)

  1. Number of participants that respond to treatment

    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.

    Measured: 18 months post treatment

  2. Time from treatment until disease progression or death

    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

    Measured: 18 months post treatment

  3. Number of participants encountering toxicity at each dose level

    Patients will potentially be treated with 3 different dose levels of ribociclib in combination with platinum-based chemotherapy.

    Measured: 30 days post treatment

  4. Overall Survival (OS)

    The (median) length of time from start of treatment patients are still alive.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2017
  2. Study start10 Jun 2017
  3. Primary completion1 Jun 2020
  4. Study completion1 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03056833
Sponsor's protocol ID
18-006
Other IDs
CLEE011XUS28T
Status last verified
Aug 2022
First submitted
14 Feb 2017
Last updated
7 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35972817

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ribociclib, Paclitaxel and Carboplatin in people with Ovarian Cancer and Fallopian Tube Cancer, run by Ronald Buckanovich at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximal tolerated dose (MTD) of ribociclib (LEE-011) when given with carboplatin + paclitaxel in platinum-sensitive recurrent ovarian cancer (time frame: 56 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03056833, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2022.

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