Paclitaxel Plus L-778,123 in Treating Patients With Recurrent or Refractory Solid Tumors or Lymphomas

June 20, 2013 updated by: Memorial Sloan Kettering Cancer Center

A Phase I and Pharmacokinetic Study Evaluating the Safety, Tolerability, and Maximally Tolerated Dose of Combination Therapy With Paclitaxel and L-778,123 in Patients With Recurrent or Refractory Solid Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining paclitaxel and L-778,123 in treating patients who have recurrent or refractory solid tumors or lymphomas.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated dose of L-778,123 when combined with paclitaxel in patients with recurrent or refractory solid tumors or lymphomas. II. Evaluate the safety, tolerability, and dose limiting toxicity of this regimen in these patients. III. Assess steady state plasma concentrations of various doses of L-778,123 combined with paclitaxel in these patients. IV. Evaluate radiologic or tumor marker responses to this regimen in these patients. V. Evaluate the relationship between ras mutations and response to this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study of L-778,123. Patients receive paclitaxel IV over 3 hours followed within 24 hours by L-778,123 IV over 7 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response receive 2 courses after documentation of response. Cohorts of 1-3 patients receive escalating doses of L-778,123 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity. Patients are followed at about 2 weeks.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

40

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
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

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

DISEASE CHARACTERISTICS: Histologically proven solid tumor or lymphoma that is recurrent or refractory to standard first line therapy Measurable or evaluable disease No active or inactive primary CNS malignancy No untreated active metastatic CNS malignancy No leukemia or plasma cell dyscrasias

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 times normal ALT or AST no greater than 2.5 times normal Alkaline phosphatase no greater than 4 times normal (no greater than 2 times normal if an increase of greater than 25% over past 2 weeks) PT, INR, or aPTT no greater than 1.2 times normal Renal: Creatinine no greater than 1.5 times normal Electrolytes within 10% of normal range Cardiovascular: No prior grade 3 or 4 cardiac arrhythmias except atrial fibrillation No QTc interval of 440 milliseconds or greater on electrocardiogram No other QTc abnormalities No myocardial infarction, unstable angina, or congestive heart failure within the past 12 months Psychiatric: No mental or legal incapacitation No concurrent significant emotional problems No prior psychiatric disorder Neurologic: No grade 2 or higher peripheral neuropathy No prior seizure disorder Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double barrier contraception or practice abstinence for at least 14 days before, during, and for at least 14 days after therapy No allergy to latex, Cremophor (found in formulations of cyclosporine or vitamin K), or paclitaxel HIV negative No HIV related malignancy No active infection No prior significant retinal disorder or disease At least 5 years since prior drug or alcohol abuse

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy No concurrent immunotherapy No concurrent colony stimulating factors or epoetin alfa Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) At least 4 weeks since prior paclitaxel and recovered No prior high dose chemotherapy with stem cell rescue No other concurrent chemotherapy Endocrine therapy: At least 4 weeks since prior endocrine therapy (except chronic LHRH agonist replacement therapy administered for at least 3 months) No concurrent endocrine therapy except prophylactic steroids during first course of chemotherapy Radiotherapy: At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery: At least 4 weeks since prior surgery No concurrent surgery Permanent indwelling central venous catheter required Other: At least 4 weeks since prior investigational agents (including FDA approved drugs for non-FDA approved indication) No concurrent medications that prolong QTc interval (e.g., terfenadine, astemizole, cisapride, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, tricyclic antidepressants, haloperidol, risperidone, indapamide, and dolasetron mesylate) No concurrent potent inducers of CYP3A (e.g., rifampin, phenobarbital, phenytoin, carbamazepine, troglitazone, and rifabutin) No concurrent benzodiazepines that are metabolized by CYP3A (e.g., triazolam, alprazolam, and midazolam) No concurrent HMG-CoA reductase inhibitors that are metabolized by CYP3A No other prophylactic medications during first course of chemotherapy except antihistamines and H2 antagonists (for paclitaxel) No more than 6 cups of coffee or the equivalent for other caffeinated beverages per day At least 24 hours since prior alcohol consumption No alcohol consumption while confined to the clinical research unit No more than 24 ounces of beer, 8 ounces of wine, or 3 ounces of whiskey or other equivalent hard liquor per day while not confined to the clinical research unit No concurrent illicit drugs No concurrent prochlorperazine

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

Collaborators and Investigators

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

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

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

December 1, 1998

Primary Completion (Actual)

December 1, 2000

Study Completion (Actual)

December 1, 2000

Study Registration Dates

First Submitted

December 10, 1999

First Submitted That Met QC Criteria

September 10, 2004

First Posted (Estimate)

September 13, 2004

Study Record Updates

Last Update Posted (Estimate)

June 21, 2013

Last Update Submitted That Met QC Criteria

June 20, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 98-116
  • CDR0000067254 (Registry Identifier: PDQ (Physician Data Query))
  • MERCK-003-04
  • NCI-G99-1572

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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