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Erlotinib and Temsirolimus for Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00770263
First received: October 8, 2008
Last updated: July 18, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Solid Tumors
Drug: Erlotinib
Drug: Temsirolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Erlotinib and Temsirolimus in Resistant Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the pharmacodynamic profile of temsirolimus in combination with erlotinib. [ Time Frame: Prior to each cycle ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To evaluate the relation between pS6K1 and p-Akt to clinical response to temsirolimus. [ Time Frame: End of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 46
Study Start Date: May 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Erlotinib
Other Name: Tarceva®
Drug: Temsirolimus
Other Name: Torisel™
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: Erlotinib
Other Name: Tarceva®
Drug: Temsirolimus
Other Name: Torisel™
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: Erlotinib
Other Name: Tarceva®
Drug: Temsirolimus
Other Name: Torisel™
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: Erlotinib
Other Name: Tarceva®
Drug: Temsirolimus
Other Name: Torisel™
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: Erlotinib
Other Name: Tarceva®
Drug: Temsirolimus
Other Name: Torisel™

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770263

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Pfizer
Investigators
Principal Investigator: Andrea Wang-Gillam, M.D., Ph.D. Washington Univerisity School of Medicine
  More Information

Additional Information:
Publications:
Hidalgo, M., Rowinsky, E, Erlichman,C, Drengler, R, Marshall, B, Marks, R, Edwards, T, Boni, J, et al., Phase I and Pharmocologic Study of CCI-779, a Cell Cycle Inhibitor. 11th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy., 2000.
Raymond, E., Alexandre, J, Depenbrock, H et al., CCI-779, a Rapamycin Analog with Antitumor Activity: A Phase I Study utilizing a Weekly Schedule. Proc Am Soc Clin Oncol, 2000.
Hidalgo, M., Rowinsky, E, Erlichman,C, et al., CCI-779, a Rapamycin Analog and Multifaceted Inhibitor of Signal Transduction: a Phase I Study. Proc Am Soc Clin Oncol, 2000. 19.
Oza, A., Elit, L, Biagi, J, Gotlieb, W, Tonkin, K, Tsao, MN, et al., A Phase II Study of Temsirolimus (CCI-779) in Patients with Metastatic and/or Recurrent Endometrial Cancer - NCI-CTG IND.160. Clin Cancer Res, 2005. 11(24): p. 9099s.
Robins, H.I., Wen, P.Y, Chang, S.M, Kuhn, K, et al., Phase I study of erlotinib and CCI-779 (temsirolimus) for patients, with recurrent malignant gliomas (MG) (NABTC 04-02). J Clin Oncol, 2007. 25(18s): p. 2057.

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00770263     History of Changes
Other Study ID Numbers: 08-1092 / 201108327
Study First Received: October 8, 2008
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
any solid tumors

Additional relevant MeSH terms:
Erlotinib
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014