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Erlotinib and Temsirolimus for Solid 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.
 
ClinicalTrials.gov Identifier: NCT00770263
Recruitment Status : Completed
First Posted : October 9, 2008
Last Update Posted : June 3, 2015
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE October 8, 2008
First Posted Date  ICMJE October 9, 2008
Last Update Posted Date June 3, 2015
Study Start Date  ICMJE May 2009
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2013)
  • To define the maximum tolerated dose and dose-limiting toxicities of temsirolimus in combination with erlotinib in patients with resistant solid malignancies. [ Time Frame: 3 years for MTD to be determined, DLT occurs in 1st cycle only ]
  • To determine the incidence and severity of other toxicities of temsirolimus in combination with erlotinib in patients with resistant solid malignancies. [ Time Frame: 30 days after end of treatment ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
  • To define the maximum tolerated dose and dose-limiting toxicities of temsirolimus in combination with erlotinib in patients with resistant solid malignancies. [ Time Frame: 3 years ]
  • To determine the incidence and severity of other toxicities of temsirolimus in combination with erlotinib in patients with resistant solid malignancies. [ Time Frame: 3 years ]
Change History Complete list of historical versions of study NCT00770263 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2013)
  • To assess the pharmacodynamic profile of temsirolimus in combination with erlotinib. [ Time Frame: Prior to each cycle ]
  • To determine any anti-tumor activity and response to the combination of temsirolimus and erlotinib in treatment of patients with resistant solid malignancies. [ Time Frame: End of treatment ]
  • To evaluate the relation between pS6K1 and p-Akt to clinical response to temsirolimus. [ Time Frame: End of treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 8, 2008)
  • To assess the pharmacokinetic profile of temsirolimus in combination with erlotinib. [ Time Frame: 3 years ]
  • To determine any anti-tumor activity and response to the combination of temsirolimus and erlotinib in treatment of patients with resistant solid malignancies. [ Time Frame: 3 years ]
  • To evaluate the relation between pS6K1 and p-Akt to clinical response to temsirolimus. [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erlotinib and Temsirolimus for Solid Tumors
Official Title  ICMJE Phase I Study of Erlotinib and Temsirolimus in Resistant Solid Malignancies
Brief Summary Define the maximum tolerated dose and dose limiting side-effects of temsirolimus in combination wtih erlotinib in patients with resistant solid tumors
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors
Intervention  ICMJE
  • Drug: Erlotinib
    Other Name: Tarceva®
  • Drug: Temsirolimus
    Other Name: Torisel™
Study Arms  ICMJE
  • Experimental: Dose Level 1A

    Erlotinib 100 mg administered orally on a once daily schedule for 35 days for the first cycle.

    Erlotinib 100 mg administered orally on a once daily schedule for 28 days for subsequent cycles.

    Temsirolimus 10 mg IV on days 8, 15, 22, and 29 during the first cycle.

    Temsirolimus 10 mg IV on days 8, 15, and 22 during subsequent cycles.

    Interventions:
    • Drug: Erlotinib
    • Drug: Temsirolimus
  • Experimental: Dose Level 1

    Erlotinib 100 mg administered orally on a once daily schedule for 35 days for the first cycle.

    Erlotinib 100 mg administered orally on a once daily schedule for 28 days for subsequent cycles.

    Temsirolimus 15 mg IV on days 8, 15, 22, and 29 during the first cycle.

    Temsirolimus 15 mg IV on days 8, 15, and 22 during subsequent cycles.

    Interventions:
    • Drug: Erlotinib
    • Drug: Temsirolimus
  • Experimental: Dose Level 2

    Erlotinib 100 mg administered orally on a once daily schedule for 35 days for the first cycle.

    Erlotinib 100 mg administered orally on a once daily schedule for 28 days for subsequent cycles.

    Temsirolimus 20 mg IV on days 8, 15, 22, and 29 during the first cycle.

    Temsirolimus 20 mg IV on days 8, 15, and 22 during subsequent cycles.

    Interventions:
    • Drug: Erlotinib
    • Drug: Temsirolimus
  • Experimental: Dose Level 3

    Erlotinib 100 mg administered orally on a once daily schedule for 35 days for the first cycle.

    Erlotinib 100 mg administered orally on a once daily schedule for 28 days for subsequent cycles.

    Temsirolimus 25 mg IV on days 8, 15, 22, and 29 during the first cycle.

    Temsirolimus 25 mg IV on days 8, 15, and 22 during subsequent cycles.

    Interventions:
    • Drug: Erlotinib
    • Drug: Temsirolimus
  • Experimental: Dose Expansion Phase

    Erlotinib 100 mg administered orally on a once daily schedule for 35 days for the first cycle.

    Erlotinib 100 mg administered orally on a once daily schedule for 28 days for subsequent cycles.

    Temsirolimus 25 mg IV on days 8, 15, 22, and 29 during the first cycle.

    Temsirolimus 25 mg IV on days 8, 15, and 22 during subsequent cycles.

    Interventions:
    • Drug: Erlotinib
    • Drug: Temsirolimus
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2014)
46
Original Estimated Enrollment  ICMJE
 (submitted: October 8, 2008)
25
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologic Diagnosis: Patients must have a histologically or cytologically proven solid malignancy which is resistant to conventional therapy or for which no effective therapy is known.
  • Dose Expansion Phase ONLY: Patients must have archived tumor tissue available (paraffin blocks, unstained tissue sections, tissue cores).
  • Tumor Mutational Status (Dose Expansion Phase ONLY): Patients must have tumor harboring PTEN loss, PIK3CA mutation, , and/or EGFR mutation. Patients cannot have KRAS or BRAF mutations. Patients must have mutational status determined by Genomic and Pathology Services at Washington University (GPS@WU) or other CLIA-certified laboratories.
  • Dose Expansion Phase ONLY: Patients with squamous carcinoma histology, papillary thyroid carcinoma, and adenoid cystic carcinoma are eligible for the expansion cohort regardless of genetic alterations..
  • Measurable or Non-Measurable Disease: Patients with measurable or non-measurable disease are eligible for entry to this study. In addition, patients without measurable or non-measurable disease are also eligible.
  • Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques (PET, CT, MRI, x-ray) or as ≥10 mm with spiral CT scan. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters).
  • Tumor markers may be considered non-measurable disease.
  • A positive bone scan, osteoblastic metastases, and pleural or peritoneal effusions are not considered measurable or non-measurable. Patients with only these lesions are eligible for entry to the study.
  • Dose Expansion Phase ONLY: Patients must have a tumor that is easily accessible for biopsy determined by the treating physician or the study PI. Patients must agree to a mandatory biopsy at the end of cycle 1 treatment.
  • Recovery from Prior Therapy: Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. No chemotherapy or radiotherapy may be given within 3 weeks prior to the start of protocol treatment. No prior therapy with erlotinib or temsirolimus allowed.
  • Age: Patients must be ≥18 years old. Because no dosing or toxicity data are currently available on the use of temsirolimus in combination with erlotinib in patients <18 years of age, children are excluded from this study, but will be eligible for the pediatric phase I single-agent trials, when available.
  • Performance Status: ECOG 0-1 at study entry.
  • Life Expectancy: Patients must have a life expectancy of greater than 12 weeks.
  • Required Laboratory Values:
  • absolute neutrophil count ≥1,500/mm3
  • platelets ≥100,000/mm3
  • hemoglobin ≥9.0 g/dL
  • total bilirubin ≤1.5 x ULN
  • AST/ALT ≤3.0 x ULN
  • alkaline phosphatase ≤2.5 x ULN
  • creatinine ≤2.0 x ULN OR
  • creatinine clearance ≥60 mL/min/1.732 for patients with creatinine levels above 2.0 mg/dl
  • serum cholesterol ≤350 mg/dL /9.0 mmol/L (fasting)
  • triglycerides ≤300 mg/dL (fasting)*
  • PT/INR ≤1.5, unless the patient is on full dose warfarin or stable dose of LMW heparin with a therapeutic INR of >1.5 - ≤3

    *Patients with triglyceride levels >400 mg/dL can be started on lipid lowering agents and reevaluated within 1 week. If levels go to ≤400 mg/dL, they can be considered for the trial and continue the lipid lowering agents.

  • Temsirolimus is primarily metabolized by CYP3A4. Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels. A partial list of agents which interact with cytochrome P450 (CYP3A) is found in Appendix AB. Use of agents that potently inhibit CYP3A (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited. Temsirolimus can inhibit CYP2D6, and may decrease metabolism (and increase drug levels) of drugs that are substrates for CYP2D6, such as codeine. The appropriateness of use of such agents is left to physician discretion. A list of drugs that may have potential interactions with CYP2D6 is found in Appendix A. If there is any doubt about eligibility based on concomitant medication, the Principal Investigator, Dr. Andrea Wang-Gillam, should be contacted. All concomitant medications must be recorded.
  • Known Allergies: Patients with known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin) are not eligible for this trial.
  • Sexually Active Patients: For all sexually active patients, the use of adequate contraception (hormonal or barrier method of birth control) will be required prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential. Pregnant and nursing women are not eligible.
  • HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV infection are excluded from the study because of possible pharmacokinetic interactions. Appropriate studies will be undertaken in patients receiving HAART therapy, when indicated.
  • Neurologic Status: Patients must not have active CNS disease.
  • Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
  • Informed Consent: Patients must have signed a Washington University Human Research Protection Office (HRPO) approved informed consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
  • Inclusion of Women and Minorities: Entry to this study is open to both men and women and to all racial and ethnic subgroups.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00770263
Other Study ID Numbers  ICMJE 08-1092 / 201108327
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D. Washington Univerisity School of Medicine
PRS Account Washington University School of Medicine
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP