A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Condition: Teratoma
MeSH terms: Teratoma
Intervention: LEE011; LEE011 Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Teratoma,; Germ Cell tumor,; incurable teratoma,; CDK4/6,; LEE011

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.
    

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