TeratomaPhase 2NCT02300987
A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
A Phase 2 study testing LEE011 in people with Teratoma, run by Novartis Pharmaceuticals at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Teratoma
- What is being tested?
- LEE011
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 26 Feb 2015to 21 Feb 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States3 sites
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, 87106
USC Kenneth Norris Comprehensive Cancer Center Oncology Dept
Los Angeles, California, 90033
Memorial Sloan Kettering Oncology Department.
New York, New York, 10017
Spain2 sites
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28041
About this study
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.
Read the 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.
- Conditions
- Teratoma
- Being tested
- LEE011, LEE011 Placebo
- Keywords
- Teratoma,, Germ Cell tumor,, incurable teratoma,, CDK4/6,, LEE011
- Medical subject headings
- Teratoma, Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011Drug
LEE011 PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| LEE011 | Active comparator | 600 mg daily dosing days 1-21 of a 28 day cycle Receives: Drug: LEE011 |
| Placebo Arm | Placebo comparator | 600 mg daily dosing days 1-21 of a 28 day cycle Receives: Drug: LEE011 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 24 months
Secondary outcomes (5)
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.
Measured: At 24 months
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
Measured: At 27 months
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.
Measured: At 24 months
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
Measured: At 27 months
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.
Measured: 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2014 (estimated)
- Study start26 Feb 2015
- Primary completion21 Feb 2018
- Study completion21 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for TeratomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02300987
- Sponsor's protocol ID
- CLEE011X2201
- Other IDs
- 2014-000428-12, 2014
- Status last verified
- Sep 2020
- First submitted
- 15 Jul 2014
- Last updated
- 26 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
- ClinicalTrials.gov ID
- NCT02300987
- Acronym / sponsor ID
- CLEE011X2201
- Conditions
- Teratoma
- Keywords
- Teratoma,, Germ Cell tumor,, incurable teratoma,, CDK4/6,, LEE011
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Feb 2015 (actual)
- Primary completion
- 21 Feb 2018 (actual)
- Study completion
- 21 Feb 2018 (actual)
- First posted
- 25 Nov 2014 (estimated)
- Results
- Posted 26 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LEE011 | Active comparator | Drug: LEE011600 mg daily dosing days 1-21 of a 28 day cycle |
| Placebo Arm | Placebo comparator | Drug: LEE011 Placebo600 mg daily dosing days 1-21 of a 28 day cycle |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEE011 | Drug | LEE011 |
| LEE011 Placebo | Drug | Placebo Arm |
Primary outcome
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.
5 secondary outcomes
Best Overall Response (BOR)
Time frame: At 24 months
Overall Response Rate
Time frame: At 27 months
Disease Control Rate (DCR)
Time frame: At 24 months
Overall Survival (OS)
Time frame: At 27 months
Overall Survival Rate
Time frame: 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LEE011 in people with Teratoma, run by Novartis Pharmaceuticals at 7 sites in 4 countries.
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 5 inclusion and 7 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 26 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Spain, France, Netherlands. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression Free Survival (PFS) (time frame: At 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Oct 2020.