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

October 1, 2020 updated by: Novartis Pharmaceuticals

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Villejuif Cedex, France, 94800
        • Novartis Investigative Site
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Madrid, Spain, 28041
        • Novartis Investigative Site
    • Catalunya
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Novartis Investigative Site
    • California
      • Los Angeles, California, United States, 90033
        • USC Kenneth Norris Comprehensive Cancer Center Oncology Dept
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • New Mexico Cancer Care Alliance
    • New York
      • New York, New York, United States, 10017
        • Memorial Sloan Kettering Oncology Department.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: LEE011
600 mg daily dosing days 1-21 of a 28 day cycle
PLACEBO_COMPARATOR: Placebo Arm
600 mg daily dosing days 1-21 of a 28 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At 24 months
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

At 27 months
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.
At 24 months
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
At 27 months
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.

1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 26, 2015

Primary Completion (ACTUAL)

February 21, 2018

Study Completion (ACTUAL)

February 21, 2018

Study Registration Dates

First Submitted

July 15, 2014

First Submitted That Met QC Criteria

November 21, 2014

First Posted (ESTIMATE)

November 25, 2014

Study Record Updates

Last Update Posted (ACTUAL)

October 26, 2020

Last Update Submitted That Met QC Criteria

October 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • CLEE011X2201
  • 2014-000428-12 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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