Back to resultsA Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Primary Purpose
Teratoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LEE011
LEE011 Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Teratoma focused on measuring Teratoma,, Germ Cell tumor,, incurable teratoma,, CDK4/6,, LEE011
Eligibility 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
Sites / Locations
- USC Kenneth Norris Comprehensive Cancer Center Oncology Dept
- New Mexico Cancer Care Alliance
- Memorial Sloan Kettering Oncology Department.
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
LEE011
Placebo Arm
Arm Description
600 mg daily dosing days 1-21 of a 28 day cycle
600 mg daily dosing days 1-21 of a 28 day cycle
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
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
Best Overall Response (BOR)
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.
Overall Response Rate
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
Disease Control Rate (DCR)
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.
Overall Survival (OS)
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
Overall Survival Rate
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.
Full Information
NCT ID
NCT02300987
First Posted
July 15, 2014
Last Updated
October 1, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02300987
Brief Title
A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Official Title
A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
February 26, 2015 (Actual)
Primary Completion Date
February 21, 2018 (Actual)
Study Completion Date
February 21, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Teratoma
Keywords
Teratoma,, Germ Cell tumor,, incurable teratoma,, CDK4/6,, LEE011
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LEE011
Arm Type
Active Comparator
Arm Description
600 mg daily dosing days 1-21 of a 28 day cycle
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
600 mg daily dosing days 1-21 of a 28 day cycle
Intervention Type
Drug
Intervention Name(s)
LEE011
Intervention Type
Drug
Intervention Name(s)
LEE011 Placebo
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
At 24 months
Secondary Outcome Measure Information:
Title
Best Overall Response (BOR)
Description
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.
Time Frame
At 24 months
Title
Overall Response Rate
Description
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
Time Frame
At 27 months
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
At 24 months
Title
Overall Survival (OS)
Description
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
Time Frame
At 27 months
Title
Overall Survival Rate
Description
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.
Time Frame
1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
USC Kenneth Norris Comprehensive Cancer Center Oncology Dept
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Memorial Sloan Kettering Oncology Department.
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94800
Country
France
Facility Name
Novartis Investigative Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing 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
Learn more about this trial
A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
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