A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors

Theodore Laetsch3 sites in 1 country4 target enrollmentJanuary 8, 2014

ConditionsRelapsed / Recurrent Germ Cell Tumors

InterventionsErlotinib Sirolimus

DrugsErlotinib Sirolimus

Overview

Phase: Phase 2
Intervention: Erlotinib
Conditions: Relapsed / Recurrent Germ Cell Tumors
Sponsor: Theodore Laetsch
Enrollment: 4
Locations: 3
Primary Endpoint: The PFR, Defined as the Proportion of Patients With Refractory Germ Cell Tumors Free of Objective Disease Progression After 4 Cycles (16 Weeks) of Therapy With Erlotinib and Sirolimus
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to find out if the combination of an mTOR inhibitor (sirolimus) with an EGFR inhibitor (erlotinib) is effective at treating relapsed or refractory germ cell tumors, and to find out what the side-effects of this regimen are.

Registry

clinicaltrials.gov

Start Date

January 8, 2014

End Date

January 27, 2018

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Theodore Laetsch

Responsible Party

Sponsor Investigator

Principal Investigator

Theodore Laetsch

Assistant Professor of Pediatrics

University of Texas Southwestern Medical Center

Eligibility Criteria

Inclusion Criteria

•Patients must be greater than 12 months and less than 50 years of age at the time of study enrollment.
•Patients must have had histologic verification of an extracranial germ cell tumor that is not a pure mature teratoma.
•Patients must have sufficient tumor tissue available to allow assessment of EGFR and mTOR pathway activation (see Section 5.2.3 for sample requirements)
•Patients must have relapsed or refractory disease following at least two prior cisplatin containing chemotherapy regimens.
•Patients must have measurable disease, documented according to RECIST criteria, or evaluable disease with a standard tumor marker (AFP and/or HCG) greater than 10 times the upper limit of normal.
•Patients must have a Lansky or Karnofsky performance status score of ≥
•Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age.
•Patients must have a life expectancy of greater than 8 weeks.
•Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
•Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment.

Exclusion Criteria

•Patients with active brain metastases are not eligible as lethal intratumoral hemorrhages have been reported with erlotinib therapy. Patients with brain metastases that have been treated and stable for \> 30 days following treatment will be eligible.
•Patients who are pregnant or breast feeding will not be entered into the study as erlotinib is teratogenic. Pregnancy tests must be obtained in females who are post-menarchal. Post-menarchal females with HCG secreting tumors will be excluded as pregnancy can't be excluded. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of the study.
•Concomitant medications
•Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
•Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible.
•Anticonvulsants: Patients who are receiving enzyme-inducing anticonvulsants are not eligible (see Appendix 1 for a list of enzyme- inducing anticonvulsants).
•Anticoagulants: Use of warfarin is not allowed while on study. Patients already on warfarin should use alternative anticoagulants while on this study. Warfarin must not have been administered within 7 days of enrollment.
•Smoking: Smoking induces CYP3A4/5 enzymes and decreases exposure to sirolimus and erlotinib. Thus, patients must not smoke for 10 days prior to enrollment and for the duration of therapy.
•Infection: Patients who have an uncontrolled infection are not eligible.
•Drug interactions: Sirolimus and erlotinib are primarily metabolized by the CYP3A4/5 enzymes. Drug exposure is substantially effected by CYP inhibitors (increased exposure) and inducers (decreased exposure). Thus, concomitant administration of strong CYP3A4/5 inhibitors or inducers is prohibited while on therapy. See Appendix 1 for a list of these medications. Patients must not have received these medications for a minimum of 10 days prior to enrollment.

Arms & Interventions

Erlotinib + sirolimus

Intervention: Erlotinib

Erlotinib + sirolimus

Intervention: Sirolimus

Outcomes

Primary Outcomes

The PFR, Defined as the Proportion of Patients With Refractory Germ Cell Tumors Free of Objective Disease Progression After 4 Cycles (16 Weeks) of Therapy With Erlotinib and Sirolimus

Time Frame: 16 weeks

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions: Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter of target lesions or the development of any new lesions

The Toxicities of the Combination of Sirolimus and Erlotinib Administered on This Schedule.

Time Frame: 2 years

The number of patients with drug related grade III, IV, or V adverse events according to the Common Terminology Criteria for Adverse Events version 4.0.

Secondary Outcomes

The Incidence of EGFR and mTOR Pathway Activation in Banked Tumor Specimens.(3 years)
The Progression-free Interval (PFI) for Patients With Germ Cell Tumors With and Without Evidence of EGFR/mTOR Pathway Activation With This Drug Combination.(3 years)