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NCT02300987

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

Completed Phase 2 Results posted Last updated 26 October 2020
What this trial tests

Phase 2 trial testing LEE011 in Teratoma in 10 participants. Completed in 21 February 2018.

Timeline
26 February 2015
Primary endpoint
21 February 2018
21 February 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingtriple
Primary purposetreatment
Enrollment10
Start date26 February 2015
Primary completion21 February 2018
Estimated completion21 February 2018
Sites7 locations across France, Netherlands, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

15 and older, any sex, with Teratoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · 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 antineopla

GroupValue95% CI
LEE01171.433.9 – 90.1
Placebo Arm0.00.0 – 0.0
Best Overall Response (BOR) Secondary · 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.

Stable Disease (SD)
GroupValue95% CI
LEE0118
Placebo Arm1
Progressive Disease (PD)
GroupValue95% CI
LEE0110
Placebo Arm1
Overall Response Rate Secondary · 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

GroupValue95% CI
LEE01100.0 – 36.9
Placebo Arm00.0 – 84.2
Disease Control Rate (DCR) Secondary · 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.

GroupValue95% CI
LEE01110063.1 – 100.0
Placebo Arm501.3 – 98.7
Overall Survival (OS) Secondary · 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

GroupValue95% CI
LEE011627.6 – 92.5
Placebo Arm10.6 – 91.0
Overall Survival Rate Secondary · 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

1 month
GroupValue95% CI
LEE011100NA – NA
Placebo Arm100NA – NA
2 months
GroupValue95% CI
LEE011100NA – NA
Placebo Arm100NA – NA
3 months
GroupValue95% CI
LEE011100NA – NA
Placebo Arm100NA – NA
6 months
GroupValue95% CI
LEE011100NA – NA
Placebo Arm100NA – NA
9 months
GroupValue95% CI
LEE011100NA – NA
Placebo Arm100NA – NA
12 months
GroupValue95% CI
LEE01187.538.7 – 98.1
Placebo Arm100NA – NA
15 months
GroupValue95% CI
LEE01187.538.7 – 98.1
Placebo Arm100NA – NA
18 months
GroupValue95% CI
LEE01187.538.7 – 98.1
Placebo Arm100NA – NA
All Collected Deaths Secondary · 12 months, 27 months

On treatment deaths are collected from first patient first visit up to 30 days after study treatment discontinuation (approximately 12 months, median duration of exposure). Patients with cancer are also followed up for overall survival until the end of the trial. During overall survival (up to 27 months after the first patient first visit), additional deaths were recorded, including deaths due to the cancer disease (having occurred more than 30 days after study drug discontinuation)

Total deaths
GroupValue95% CI
LEE0112
Placebo Arm1
Deaths on treatment
GroupValue95% CI
LEE0110
Placebo Arm0
Deaths post treatment survival follow up
GroupValue95% CI
LEE0112
Placebo Arm1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LEE011
Serious: 3/8 (38%)
Deaths: 0/8
Placebo
Serious: 0/2 (0%)
Deaths: 0/2
All Patients
Serious: 3/10 (30%)
Deaths: 0/10

Serious adverse events (10 terms)

ReactionSystemLEE011PlaceboAll Patients
VomitingGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Meningitis bacterialInfections and infestations
PneumoniaInfections and infestations
Blood creatinine increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HeadacheNervous system disorders
Acute kidney injuryRenal and urinary disorders
HypotensionVascular disorders
Other adverse events (74 terms — click to expand)

ReactionSystemLEE011PlaceboAll Patients
HeadacheNervous system disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
AnaemiaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Blood creatinine increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Night sweatsSkin and subcutaneous tissue disorders
LeukopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
PalpitationsCardiac disorders
Dermoid cystCongenital, familial and genetic disorders
Ear painEar and labyrinth disorders
TinnitusEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
StomatitisGastrointestinal disorders
Breakthrough painGeneral disorders
Chest painGeneral disorders
Impaired healingGeneral disorders
MalaiseGeneral disorders
PainGeneral disorders
Anal infectionInfections and infestations
Fungal infectionInfections and infestations
LaryngitisInfections and infestations
NasopharyngitisInfections and infestations
RhinitisInfections and infestations
Urinary tract infectionInfections and infestations

Most-reported serious reactions: Vomiting, Fatigue, Pyrexia, Meningitis bacterial, Pneumonia, Blood creatinine increased, Decreased appetite, Headache.

Data from ClinicalTrials.gov NCT02300987 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cyclin D1, cancer progression, and opportunities in cancer treatment.
    Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
  2. CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors.
    Schettini F, De Santo I, Rea CG, De Placido P, et al · · 2018 · cited 150× · PMID 30631751 · DOI 10.3389/fonc.2018.00608
  3. CDK4/6 inhibition presents as a therapeutic option for paediatric and adult germ cell tumours and induces cell cycle arrest and apoptosis via canonical and non-canonical mechanisms.
    Skowron MA, Vermeulen M, Winkelhausen A, Becker TK, et al · · 2020 · cited 36× · PMID 32418994 · DOI 10.1038/s41416-020-0891-x
  4. Recent advances of cyclin-dependent kinases as potential therapeutic targets in HR+/HER2- metastatic breast cancer: a focus on ribociclib.
    Edessa D, Sisay M. · · 2017 · cited 11× · PMID 29263697 · DOI 10.2147/bctt.s150540
  5. Recent advances in testicular germ cell tumours.
    Mele T, Reid A, Huddart R. · · 2021 · cited 10× · PMID 34557871 · DOI 10.12703/r/10-67

Verify or expand the search:

Other trials of LEE011

Trials testing the same drug.

Other recruiting trials for Teratoma

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing