Erlotinib and Temsirolimus for Solid Tumors

June 2, 2015 updated by: Washington University School of Medicine

Phase I Study of Erlotinib and Temsirolimus in Resistant Solid Malignancies

Define the maximum tolerated dose and dose limiting side-effects of temsirolimus in combination wtih erlotinib in patients with resistant solid tumors

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Temsirolimus
Other Names:
  • Torisel™
Drug: Erlotinib
Other Names:
  • Tarceva®
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.
Drug: Temsirolimus
Other Names:
  • Torisel™
Drug: Erlotinib
Other Names:
  • Tarceva®
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.
Drug: Temsirolimus
Other Names:
  • Torisel™
Drug: Erlotinib
Other Names:
  • Tarceva®
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.
Drug: Temsirolimus
Other Names:
  • Torisel™
Drug: Erlotinib
Other Names:
  • Tarceva®
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.
Drug: Temsirolimus
Other Names:
  • Torisel™
Drug: Erlotinib
Other Names:
  • Tarceva®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
30 days after end of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the pharmacodynamic profile of temsirolimus in combination with erlotinib.
Time Frame: Prior to each cycle
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
End of treatment
To evaluate the relation between pS6K1 and p-Akt to clinical response to temsirolimus.
Time Frame: End of treatment
End of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Pfizer

Investigators

  • Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D., Washington Univerisity School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

October 8, 2008

First Submitted That Met QC Criteria

October 8, 2008

First Posted (Estimate)

October 9, 2008

Study Record Updates

Last Update Posted (Estimate)

June 3, 2015

Last Update Submitted That Met QC Criteria

June 2, 2015

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-1092 / 201108327

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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