Study of Temsirolimus, Erlotinib and Cisplatin in Solid Tumors

NCT00998036 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAD8279
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I research study designed to determine the maximum tolerated dose (MTD) of cisplatin, temsirolimus, and erlotinib in combination for treatment in triple negative breast cancer (TNBC) patients.

Conditions

Triple Negative Breast Cancer

Keywords

TNBC; Temsirolimus; Erlotinib; Cisplatin; Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of Cisplatin

  MTD of the drug as part of combination therapy will be determined.

  6 months

• MTD of Temsirolimus

  MTD of the drug as part of combination therapy will be determined.

  6 months

• MTD of Erlotinib

  MTD of the drug as part of combination therapy will be determined.

  6 months

Study Arms (1)

Temsirolimus, cisplatin, erlotinib

EXPERIMENTAL

Cisplatin and temsirolimus will be administered weekly on days one and eight of a three week cycle. Erlotinib will be taken by mouth daily.

Drug: Temsirolimus; Drug: Cisplatin; Drug: Erlotinib

Interventions

Temsirolimus DRUG

Temsirolimus will be administered intravenously weekly on days one and eight of a three week cycle. Temsirolimus will not be given on week three (usually dosed weekly) for increased tolerability given its possible plasma accumulation during week three. Temsirolimus will be given second over a 30 minute infusion during posthydration. Dose escalation will follow the standard 3 by 3 design with three set dosing levels. Dose Level 1: Temsirolimus 15mg Dose Level 2: Temsirolimus 15mg Dose Level 3: Temsirolimus 25mg

Also known as: Torisel

Temsirolimus, cisplatin, erlotinib

Cisplatin DRUG

Cisplatin at 30mg/m2 will be administered intravenously weekly on days one and eight of a three week cycle. Cisplatin will be given first over a 30 minute infusion with prehydration.

Also known as: Platinol

Temsirolimus, cisplatin, erlotinib

Erlotinib DRUG

Erlotinib will be taken by mouth daily starting at 100mg. On days of cisplatin and temsirolimus infusions, erlotinib should be taken at least two hours after the beginning of the temsirolimus infusion. Dose escalation will follow the standard 3 by 3 design with three set dosing levels. Dose Level 1: Erlotinib 100mg Dose Level 2: Erlotinib 150mg Dose Level 3: Erlotinib 150mg

Also known as: Tarceva

Temsirolimus, cisplatin, erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which the combination of cisplatin, temsirolimus, and erlotinib is a reasonable treatment.
• Patients with measurable or non-measurable disease are eligible for entry to this study. Tumor markers may be considered non-measurable disease.
• 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.
• Patients must be ≥18 years old.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1
• Life expectancy of greater than 12 weeks.
• 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.
• Required Laboratory Values: absolute neutrophil count (ANC) ≥1,500/mm3, platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL, total bilirubin ≤1.5 x upper limit of normal (ULN), aspartate transaminase (AST)/alanine transaminase (ALT) ≤3.0 x ULN, alkaline phosphatase ≤2.5 x ULN, creatinine ≤2.0 x ULN OR Patients must have either a normal serum creatinine (\<= IULN) OR estimated creatinine clearance 60 ml/min (Cockcroft-Gault formula) within 28 days prior to registration. Prothrombin time (PT)/INR ≤1.5, unless the patient is on full dose warfarin or stable dose of low-molecular-weight (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.
• Concomitant Medications: Temsirolimus and Erlotinib are primarily metabolized by CYP3A4. Patients CANNOT be receiving enzyme-inducing or enzyme inhibiting agents listed here: Inhibitors: Amiodarone, Amprenavir, Atazanavir, Chloramphenicol, Clarithromycin, Conivaptan, Cyclosporine, Darunavir, Dasatinib, Delavirdine, Diltiazem, Erythromycin, Fluconazole, Fluoxetine, Fluvoxamine, Fosamprenavir, Imatinib, Indinavir, Isoniazid, Itraconazole, Ketoconazole, Lapatinib, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Quinupristin, Saquinavir, Tamoxifen, Telithromycin, Troleandomycin, Verapamil, Voriconazole. Inducers: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort, Sulfadimidine, Sulfinpyrazone, Troglitazone, Troleandomycin. All concomitant medications must be recorded. Patients also must agree to refrain from drinking grapefruit juice while on study.
• 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.
• Patients must have signed an approved informed consent.

You may not qualify if:

• More than 3 prior chemotherapy treatments for metastatic disease.
• Patients receiving anti-retroviral therapy (HAART) for HIV infection because of possible pharmacokinetic interactions.
• Active central nervous system (CNS) disease
• Any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
• Patients pregnant or nursing.
• Patients who have used tobacco or nicotine products containing medications within the last three months given their significant effect on erlotinib drug levels.

Sponsors & Collaborators

• Columbia University: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

temsirolimus; Cisplatin; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kevin Kalinksy, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 19, 2009
• First Posted: October 20, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 13, 2017

Record last verified: 2017-12

Locations

US (1)