Study for patients with relapsed, refractory, incurable teratoma with recent progression. The study is randomized (the patient may receive the investigational drug or placebo) and it is blinded (the patient and the study doctor will not know what drug the patient receives).

Phase 1

• Conditions: relapsed, refractory, incurable teratoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000428-12-FR
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-08
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1.Age = 15 years old at time of informed consent.
2.Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
3.Availability of an archival tumor biopsy specimen (collected at diagnosis or progression) with accompanying pathology report
•Patients without an archival tumor sample may be permitted to participate after discussion between Novartis and the investigator
4.Patients must have completed at least 1 prior line of chemotherapy for germ cell tumor
5.If malignant transformation is present then chemotherapy appropriate for malignant transformation histology must have been given
6. 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.
7.Measurable or evaluable extra-cranial disease as defined by RECIST v.1.1
8.Patients must have ECOG performance status of 0-1

Other criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation by CT (with contrast enhancement) or MRI over a minimum of 3 months demonstrates stable disease. Patient must be asymptomatic and without need for treatment with systemic corticosteroids or anti-epileptic medications
2.Malignant germ cell tumors other than that being treated in this study, including tumors with elements of mixed histology such as embryonal carcinoma, choriocarcinoma, yolk sac tumor or seminoma
3.Concurrent malignancy other than teratoma or malignancy within 3 years of randomization, with the exception of adequately treated basal or squamous cell carcinoma of the skin, curatively resected cervical cancer or curatively resected carcinoma in situ of any type
4.Prior treatment with any CDK4/6 inhibitor therapy
5.Any concurrent severe and/or uncontrolled medical condition that, in the investigator’s judgment serves as a contraindication to patient participation (e.g., chronic pancreatitis, active hepatitis, viral hepatitis or known HIV positivity. Baseline HIV screening is not required
6.Patients who have not recovered to = CTCAE grade 1 from the acute toxic effects (except for alopecia) of all prior chemotherapy, immunotherapy, or radiotherapy
7.Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
8.Impaired cardiac function or any clinically significant cardiac disease, including any of the following
•Left ventricular ejection fraction (LVEF) < 45% or less than the institution’s lower limit of normal as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO)
•Congenital long QT syndrome or family history of unexpected sudden cardiac death
•QT corrected with Fredericia’s (QTcF) QTcF >450 msec for males and >470 msec for females on screening ECG
•Clinically significant heart disease such as CHF requiring treatment (NYH grade = 2), unstable angina pectoris or myocardial infarction within the past 3 months. Any other clinically significant heart disease such as unstable arrhythmia, resting bradycardia, right bundle branch block, bifascicular block, or any heart disease that requires the use of a cardiac pacemaker = 3 months prior to starting study drug
•Patients who are currently receiving medications with known risk of prolonging the QT interval or inducing Torsades de Pointes and are unable to discontinue or switch to an alternate medication
9.Concomitant therapy that precludes enrollment
•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)
•Systemic corticosteroids within 2 weeks prior to starting study drug. Note: Corticosteroids are permitted for use as single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
10.Major surgery within 2 weeks prior to planned start of study drug or patient has not recovered from major side effects of the surgery
11.Received radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to randomization, or patient has not recovered to = CTCAE grade 1 related toxicity
12.Requirement for treatment with any of the prohibited medications in

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of LEE011 compared to placebo in patients with relapsed/refractory teratoma with recent progression;Secondary Objective: 1.To assess other measures of efficacy of LEE011 compared with placebo<br>2.To assess safety and tolerability of LEE011 compared with placebo<br>;Primary end point(s): Progression Free Survival (PFS) as per RECIST v1.1 (by local investigator assessment);Timepoint(s) of evaluation of this end point: -Evaluated after at least 25 and approximately 62 PFS events have been documented for the interim analysis and primary CSR, respectively.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Best Overall Response (BOR),Overall response rate (ORR) and Disease Control Rate (DCR) as per RECIST v1.1, Overall Survival (OS) and OS rate <br><br>2. Incidence and severity of adverse events and serious adverse events, changes in laboratory values, and electrocardiograms will be used to assess the safety as per CTCAE v.4.03. Dose interruptions and changes will be used to assess the tolerability.<br><br>;Timepoint(s) of evaluation of this end point: -All secondary endpoints will be evaluated after at least 25 and approximately 62 PFS events have been documented for the interim analysis and primary CSR, respectively.