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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01962896
Recruitment Status : Terminated (Low accrual)
First Posted : October 14, 2013
Results First Posted : February 26, 2019
Last Update Posted : February 26, 2019
Information provided by (Responsible Party):
Theodore Laetsch, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Relapsed / Recurrent Germ Cell Tumors Drug: Erlotinib Drug: Sirolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors
Actual Study Start Date : January 8, 2014
Actual Primary Completion Date : June 13, 2017
Actual Study Completion Date : January 27, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Erlotinib + sirolimus Drug: Erlotinib
Drug: Sirolimus

Primary Outcome Measures :
  1. 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

  2. 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 Outcome Measures :
  1. The Incidence of EGFR and mTOR Pathway Activation in Banked Tumor Specimens. [ Time Frame: 3 years ]
  2. The Progression-free Interval (PFI) for Patients With Germ Cell Tumors With and Without Evidence of EGFR/mTOR Pathway Activation With This Drug Combination. [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 ≥ 50. 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.
    • Patients must be > 7 days since treatment with hematopoetic growth factors (>14 days for Neulasta).
    • Patients must be >7 days since therapy with a biologic agent and beyond the period for which adverse events of the biologic agent are known to occur if longer.
    • Patients must be >3 half-lives since therapy with a monoclonal antibody.
    • Patients must be >42 days since completion of any immunotherapy (i.e. tumor vaccines).
    • Patients must be greater than 2 weeks since most recent palliative XRT and greater than 6 weeks since substantial bone marrow irradiation.
    • Patients must be greater than 8 weeks since prior stem cell transplant or infusion and without evidence of active graft vs. host disease.
  • Adequate bone marrow function defined as:

    • Peripheral absolute neutrophil count (ANC) of at least 1,000/ L
    • Platelet count of at least 100,000/ L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)
    • Hemoglobin 8.0 g/dL (may receive RBC transfusions).
  • Adequate renal function defined as:

    • Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or
    • Maximum serum creatinine (mg/dL) based on age/gender
  • Adequate liver function defined as:

    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
    • SGPT (ALT) ≤ 2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)
    • Serum albumin ≥ 2 g/dL.
  • Adequate central nervous system function defined as:

    o Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled.

  • Serum cholesterol levels must be less than Grade 2 (< 300 mg/dL), and serum triglyceride levels must be less than Grade 2 (< 2.5 x ULN).

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.
  • Patients who have received prior therapy targeting EGFR with small molecule tyrosine kinase inhibitors or monoclonal antibodies are NOT eligible.
  • Prior treatment with mTOR or TORC1/2 inhibitors (eg, rapamycin, temsirolimus, everolimus, sirolimus) is NOT allowed.
  • Patients who have had major surgery within 3 weeks prior to enrollment are not eligible. Procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01962896

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United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
UT Southwestern Medical Center/Children's Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Theodore Laetsch
  Study Documents (Full-Text)

Documents provided by Theodore Laetsch, University of Texas Southwestern Medical Center:

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Responsible Party: Theodore Laetsch, Assistant Professor of Pediatrics, University of Texas Southwestern Medical Center Identifier: NCT01962896     History of Changes
Other Study ID Numbers: UTSW-GCT-001
First Posted: October 14, 2013    Key Record Dates
Results First Posted: February 26, 2019
Last Update Posted: February 26, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs