Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02300987
Recruitment Status : Completed
First Posted : November 25, 2014
Results First Posted : October 26, 2020
Last Update Posted : October 26, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

This was a multi-center, randomized, double blind (investigator and subject), placebo controlled Phase II study to determine the efficacy and safety of treatment with ribociclib versus placebo in subjects with progressive relapsed, refractory incurable teratoma. Eligible subjects were randomized in a 2:1 ratio to ribociclib or placebo.

After discontinuation of study treatment, patients were followed up for safety, disease progression and overall survival.


Condition or disease Intervention/treatment Phase
Teratoma Drug: LEE011 Drug: LEE011 Placebo Phase 2

Detailed Description:

Safety follow-up: After discontinuation of study treatment, all subjects were followed for safety for 30 days except in the case of death, loss to follow up, withdrawal of consent, or discontinuation of study treatment to enroll in the ribociclib rollover clinical trial (CLEE011X2X01B).

Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.

Survival follow-up: All subjects were followed for survival via a phone call (or during a clinic visit) every 12 weeks and up to one additional time per quarter if a survival update was required to meet safety or regulatory needs. The safety follow-up was carried out until any of the following occurred (whichever occurred first): death, withdrawal of consent, loss to follow-up, at least 18 months had elapsed from when the last subject had started treatment, or when 80% of subjects had died or were lost to follow-up, or early study termination.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Actual Study Start Date : February 26, 2015
Actual Primary Completion Date : February 21, 2018
Actual Study Completion Date : February 21, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ribociclib

Arm Intervention/treatment
Active Comparator: LEE011
600 mg daily dosing days 1-21 of a 28 day cycle
Drug: LEE011
Placebo Comparator: Placebo Arm
600 mg daily dosing days 1-21 of a 28 day cycle
Drug: LEE011 Placebo



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: At 24 months ]
    Date of randomization to the date of the first documented progression or death due to any causeas per RECIST v1.1 (by local investigator assessment). Only includes data prior to cross over. Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.


Secondary Outcome Measures :
  1. Best Overall Response (BOR) [ Time Frame: At 24 months ]
    as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the subject who experienced SD as best overall response entered the secondary phase and was treated with LEE011 after he experienced progressive disease, following his best Stable Disease response. In this outcome measure 2, only the best overall response is indicated.

  2. Overall Response Rate [ Time Frame: At 27 months ]

    Overall response rate (ORR) = complete response (CR) or partial response (PR).

    ORR was zero, as there were no CRs or PRs in either of the groups


  3. Disease Control Rate (DCR) [ Time Frame: At 24 months ]
    as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the disease control rate is based on the best overall response described in the outcome measure 2.

  4. Overall Survival (OS) [ Time Frame: At 27 months ]
    Only includes data prior to cross over. OS defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut off, OS was censored at the date of last known date patient alive

  5. Overall Survival Rate [ Time Frame: 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months ]

    as per RECIST v1.1. Only includes data prior to cross over. Kaplan-Meier estimates (%) OS rate [95% CI] at different timepoints. The overall survival rate at 27 month is 72.9% by Kaplan-Meyer (K-M) estimator; the reason that it is not 75% (1-25%) (Overall survival) is because of censoring. When the other 6 patients were censored would impact the survival rate with K-M method as the number of patients at risk after each censor was changed.

    NA for the 95% CI is indicated when no patient died at the time of assessment, as the CI could not be calculated as per definition. Results are presented as a % calculated on the total number of participants.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
  • Patients must have completed at least 1 prior line of chemotherapy for germ cell tumor (except patients who present with primary pure teratoma who need not have received any previous chemotherapy)
  • Radiographic progression, defined by RECIST v.1.1, after the last cancer treatment and within 12 weeks prior to enrollment, compared with scans within 1 year of enrollment.
  • Availability of an archival or newly obtained tumor sample (collected at diagnosis or progression) with accompanying pathology report
  • Meaurable or evaluable extra-cranial disease as defined by RECIST v 1.1

Key Exclusion Criteria:

  • Malignant germ cell tumors with mixed histology such as embryonal carcinoma, choriocarcinoma, yolk sac tumor or seminoma. Note - this refers to the histology at the time of enrollment, not the histolgy at the time of initial presentation.
  • Pathologic evidence of malignant transformation
  • CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease
  • Prior treatment with any CDK4/6 inhibitor therapy
  • Systemic antineoplastic therapy or any experimental therapy within 3 weeks before the first dose of study drug (6 weeks for prior nitrosoureas, bevacizumab, or mitomycin C)
  • Major surgery ≤ 2 weeks or radiotherapy ≤ 4 weeks prior to planned start of study drug or patient has not recovered from major side effects.
  • Requirement for treatment with any of the prohibited medications including strong CYP3A inhibitors, strong CYP3A inducers, CYP3A substrates with a narrow therapeutic index, and medications with strong risk of QT prolongation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02300987


Locations
Layout table for location information
United States, California
USC Kenneth Norris Comprehensive Cancer Center Oncology Dept
Los Angeles, California, United States, 90033
United States, New Mexico
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, United States, 87106
United States, New York
Memorial Sloan Kettering Oncology Department.
New York, New York, United States, 10017
France
Novartis Investigative Site
Villejuif Cedex, France, 94800
Netherlands
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Spain
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Madrid, Spain, 28041
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] August 18, 2017
Statistical Analysis Plan  [PDF] December 7, 2016

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02300987    
Other Study ID Numbers: CLEE011X2201
2014-000428-12 ( EudraCT Number )
First Posted: November 25, 2014    Key Record Dates
Results First Posted: October 26, 2020
Last Update Posted: October 26, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Teratoma,
Germ Cell tumor,
incurable teratoma,
CDK4/6,
LEE011
Additional relevant MeSH terms:
Layout table for MeSH terms
Teratoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms