Relapsed / Recurrent Germ Cell TumorsPhase 2NCT01962896
A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors
A Phase 2 study testing Erlotinib and Sirolimus in people with Relapsed / Recurrent Germ Cell Tumors, run by Theodore Laetsch at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 months to 50 years
- Conditions the study is for
- Relapsed / Recurrent Germ Cell Tumors
- What is being tested?
- Erlotinib and Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesUnited States
- Study dates
- 8 Jan 2014to 27 Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 29Show fewer
- 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).
Who cannot join
- 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).
Show all 14Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
UT Southwestern Medical Center/Children's Medical Center
Dallas, Texas, 75390
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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.
- Conditions
- Relapsed / Recurrent Germ Cell Tumors
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + sirolimus | Experimental | Not described Receives: Drug: Erlotinib; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: 16 weeks
The Toxicities of the Combination of Sirolimus and Erlotinib Administered on This Schedule.
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.
Measured: 2 years
Secondary outcomes (2)
The Incidence of EGFR and mTOR Pathway Activation in Banked Tumor Specimens.
Measured: 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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2013 (estimated)
- Study start8 Jan 2014
- Primary completion13 Jun 2017
- Study completion27 Jan 2018
Why it stopped: Low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed / Recurrent Germ Cell TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theodore Laetsch
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Theodore Laetsch, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01962896
- Sponsor's protocol ID
- UTSW-GCT-001
- Status last verified
- Feb 2019
- First submitted
- 20 Sep 2013
- Last updated
- 26 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors
- ClinicalTrials.gov ID
- NCT01962896
- Acronym / sponsor ID
- UTSW-GCT-001
- Conditions
- Relapsed / Recurrent Germ Cell Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Theodore LaetschUniversity, hospital or other
- Study start
- 8 Jan 2014 (actual)
- Primary completion
- 13 Jun 2017 (actual)
- Study completion
- 27 Jan 2018 (actual)
- First posted
- 14 Oct 2013 (estimated)
- Results
- Posted 26 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + sirolimus | Experimental | Drug: Erlotinib, Drug: Sirolimus |
Who may qualify
- Ages
- 12 months to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (29 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erlotinib | Drug | Erlotinib + sirolimus |
| Sirolimus | Drug | Erlotinib + sirolimus |
Primary outcome
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.
2 secondary outcomes
The Incidence of EGFR and mTOR Pathway Activation in Banked Tumor Specimens.
Time frame: 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.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Relapsed / Recurrent Germ Cell Tumors
RecruitingPhase 1/2
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Recurrent Ganglioneuroblastoma, Recurrent Neuroblastoma
RecruitingPhase 1
Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
Recurrent Small Cell Lung Cancer, Extensive-Stage Small Cell Lung Cancer
Active, not recruitingPhase 2
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm
RecruitingPhase 1/2
Novel Indenoisoquinolone CMYC/TOPOISOMERASE 1 Inhibitor (LMP744) in Recurrent Glioblastoma
Recurrent Glioblastoma, Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype
Active, not recruitingPhase 2
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Advanced Malignant Solid Neoplasm, Recurrent Childhood Ependymoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erlotinib and Sirolimus in people with Relapsed / Recurrent Germ Cell Tumors, run by Theodore Laetsch at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2019.