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

NCT02300987 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLEE011X22012014-000428-12
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 7

Brief 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.

Conditions

Teratoma

Keywords

Teratoma,; Germ Cell tumor,; incurable teratoma,; CDK4/6,; LEE011

Outcome Measures

Primary Outcomes (1)

• 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.

  At 24 months

Secondary Outcomes (5)

• Best Overall Response (BOR)

  At 24 months

• Overall Response Rate

  At 27 months

• Disease Control Rate (DCR)

  At 24 months

• Overall Survival (OS)

  At 27 months

• Overall Survival Rate

  1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months

Study Arms (2)

LEE011

ACTIVE COMPARATOR

600 mg daily dosing days 1-21 of a 28 day cycle

Drug: LEE011

Placebo Arm

PLACEBO COMPARATOR

600 mg daily dosing days 1-21 of a 28 day cycle

Drug: LEE011 Placebo

Interventions

LEE011 DRUG

LEE011

LEE011 Placebo DRUG

Placebo Arm

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

USC Kenneth Norris Comprehensive Cancer Center Oncology Dept

Los Angeles, California, 90033, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Memorial Sloan Kettering Oncology Department.

New York, New York, 10017, United States

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Teratoma; Neoplasms, Germ Cell and Embryonal

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

After 10 patients were included the recruitment was halted for business reasons not for safety concerns. Overall Survival presents all deaths up to 27 months while the all-cause mortality presents deaths up to 30 days after treatment discontinuation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

1-888-669-6682

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2014
• First Posted: November 25, 2014
• Study Start: February 26, 2015
• Primary Completion: February 21, 2018
• Study Completion: February 21, 2018
• Last Updated: October 26, 2020
• Results First Posted: October 26, 2020

Record last verified: 2020-09

Locations

NL (1); US (3); ES (2); FR (1)