PrimaryTo assess the efficacy of LEE011 compared to placebo in patients with relapsed/refractory teratoma with recent progressionSecondaryTo assess other measures of efficacy of LEE011 compared with placebo To assess safety and tolerability of…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free Survival (PFS) as per RECIST v1.1
Secondary outcome
Best Overall Response (BOR),
Overall response rate (ORR)
Disease Control Rate (DCR) at 4 months as per RECIST v1.1,
Overall Survival (OS), and OS rate at 12 months.
Incidence and severity of adverse events, serious adverse events, changes in
laboratory values, electrocardiograms, and vital signs to assess the safety as
per CTCAE v.4.03.
Dose interruptions and changes will be used to assess the tolerability.
Background summary
Teratomas consist of cell types derived from one or more of the germ layers and
arise most commonly in the gonads or midline structures Teratoma
classification is dichotomized into benign and malignant. Benign teratomas are
distinguished as mature or immature based on the proportion of differentiated
tissue observed. Malignant teratomas include mature/immature teratomas that
have metastasized or contain non-germinal malignant patterns (malignant
transformation) Teratomas may also arise within other germ cell tumor (GCT)
types, most commonly non-seminomatous germ cell tumors (NSGCT).
Malignant teratoma is rare in both the pediatric and adult populations with an
incidence of 0.14/100,000 women-years . The frequency is higher in males.
Malignant transformation (MT) of teratomatous elements arises in 3-6% of
testicular NSGCT and progressive localized growth of teratoma. The US incidence
of testicular GCT is 5.7/100,000 males, The incidence of testicular cancer is
similar in Western Europe and Australia
Unlike NSGCTs which are sensitive to cytotoxic chemotherapy, teratomas are
highly chemo-resistant and optimally treated by complete surgical resection.
More than 80% of cases of GTS are successfully managed by surgical resection.
Evidence of teratoma with malignant transformation at initial presentation of
NSGCT may also be successfully managed with intensive chemotherapy and
extensive resection. However, no standard therapy exists for progressive,
unresectable teratoma Given the known deregulation of the RB tumor suppressor
pathway in GCTs and that nearly all malignant teratomas stain positively for
nuclear pRB, treatment of non-resectable malignant teratoma with a CDK 4/6
inhibitor such as LEE011 is a rational approach.
Study objective
Primary
To assess the efficacy of LEE011 compared to placebo in patients with
relapsed/refractory teratoma with recent progression
Secondary
To assess other measures of efficacy of LEE011 compared with placebo
To assess safety and tolerability of LEE011 compared with placebo
Study design
multi-center, randomized, double blind, placebo controlled phase II study
randomized at a 2:1 ratio to LEE011 or placebo
Intervention
600mg LEE011 Capsule for oral use Daily (21 days followed by one week break)
Placebo Capsule for oral use Daily (21 days followed by one
week break)
Study burden and risks
Risks: toxicities due to the study drug: LEE011
Burden: cycles of 28 days, with 2 visites per cycle.
Blooddraws as specified in section J, inclusive PK sampling
ECGs
MUGA scan and CT scan (see section J)
optional Tumor biopsies
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
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 or newly obtained tumor sample accompanying pathology report.
* Patients without a 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. 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.
6. Measurable or evaluable extra-cranial disease as defined by RECIST v.1.1.
7. Patients must have ECOG performance status of 0-1.
8. Written informed consent/assent before any study-specific screening procedures.
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 2 months demonstrates stable disease.
2. Malignant germ cell tumors other than that being treated in this study
3. Concurrent malignancy other than teratoma within 3 years of randomization
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
6. Patients who have not recovered to * CTCAE grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000428-12-NL |
| ClinicalTrials.gov | NCT02300987 |
| CCMO | NL50782.042.14 |