LY231514 in Treating Patients With Locally Advanced or Metastatic Solid Tumors and Varying Degrees of Kidney Function

• ClinicalTrials.gov Identifier: NCT00003706
• Recruitment Status: Completed
• First Posted: March 15, 2004
• Last Update Posted: June 28, 2012
• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Lily Research Laboratories; National Cancer Institute (NCI)
• Information provided by (Responsible Party): The University of Texas Health Science Center at San Antonio

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: March 15, 2004
• Last Update Posted Date: June 28, 2012
• Study Start Date: April 1998
• Actual Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: LY231514 in Treating Patients With Locally Advanced or Metastatic Solid Tumors and Varying Degrees of Kidney Function
• Official Title: A Phase I Pharmacokinetic Trial of LY231514 Administered Intravenously Every 3 Weeks in Advanced Cancer Patients With Varying Degrees of Renal Function

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemotherapy drugs may have different effects in patients with different degrees of kidney function.

PURPOSE: Phase I trial to study the effectiveness of LY231514 in treating patients who have locally advanced or metastatic solid tumors and varying degrees of kidney function.

Detailed Description

OBJECTIVES: I. Determine the toxic effects and maximum tolerated dose (MTD) of LY231514 in patients with metastatic or locally advanced solid tumors and varying degrees of renal function. II. Determine the recommended dose for LY231514 in this patient population. III. Examine the effects of renal dysfunction on the pharmacokinetics of LY231514 in this patient population. IV. Examine the relationship between impaired renal function, drug exposure, and drug effects in these patients. V. Gather data for development of a LY231514 dosing nomogram based on renal function. VI. Collect preliminary data regarding antitumor effects of LY231514 in this patient population.

OUTLINE: This is an open label, dose escalation study. Patients are stratified according to renal function. Group 1 consists of patients with normal renal function, and groups 2, 3, and 4 consist of patients with mild, moderate, and severe renal impairment. All patients receive LY231514 IV over 10 minutes every 3 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients are treated with escalating doses of LY231514 within each treatment group. If dose limiting toxicity (DLT) is observed in 1 of 3 patients at a given dose level, then 3 additional patients are studied. The maximum tolerated dose is defined as the dose level at which less than 2 of 6 patients experience DLT. Patients are followed until death.

PROJECTED ACCRUAL: Up to 50 patients will be accrued for this study.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention: Drug: pemetrexed disodium
• Study Arms: Not Provided
• Publications *: Mita AC, Sweeney CJ, Baker SD, Goetz A, Hammond LA, Patnaik A, Tolcher AW, Villalona-Calero M, Sandler A, Chaudhuri T, Molpus K, Latz JE, Simms L, Chaudhary AK, Johnson RD, Rowinsky EK, Takimoto CH. Phase I and pharmacokinetic study of pemetrexed administered every 3 weeks to advanced cancer patients with normal and impaired renal function. J Clin Oncol. 2006 Feb 1;24(4):552-62. Epub 2006 Jan 3.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 9, 2007): 50
• Original Enrollment: Not Provided
• Actual Study Completion Date: June 2002
• Actual Primary Completion Date: June 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic or locally advanced solid tumors that have failed standard therapy or for which no standard therapy exists Measurable or evaluable disease No active, symptomatic brain metastases No leukemia, lymphoma, or multiple myeloma No significant pleural or peritoneal effusions

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks 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 upper limit of normal (ULN) AST and ALT no greater than 3 times ULN (no greater than 5 times ULN if due to liver disease) Albumin at least 2.0 g/dL Renal: Not specified Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study No active infection or serious concurrent systemic disorders No second primary malignancy in the past 5 years except carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin No body surface area greater than 3 m2

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy No concurrent routine use of filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) and recovered No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy (except contraceptives and corticosteroids) Radiotherapy: At least 4 weeks since prior radiotherapy (including wide field pelvic radiation) No concurrent radiotherapy Surgery: Not specified Other: At least 4 weeks since prior investigational agents Concurrent warfarin and heparin allowed No aspirin and other nonsteroidal antiinflammatory 2 days before, the day of, and 2 days after LY231514 administration (5 days for long-acting agents) No concurrent nonsteroidal antiinflammatory drugs or salicylates with a long half-life e.g., naproxen, piroxicam, diflunisal, or nabumetone) No other concurrent experimental medications No concurrent dialysis

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00003706
• Other Study ID Numbers: CDR0000066814; P30CA054174 ( U.S. NIH Grant/Contract ); UTHSC-9785011141 ( Other Identifier: UTHSCSA IRB ); LILLY-H3E-MC-JMAW(a) ( Other Identifier: Eli Lilly ); SACI-IDD-97-29 ( Other Identifier: San Antonio Cancer Institute ); NCI-V98-1500 ( Other Identifier: NCI )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: The University of Texas Health Science Center at San Antonio
• Study Sponsor: The University of Texas Health Science Center at San Antonio

Collaborators

• Lily Research Laboratories
• National Cancer Institute (NCI)

Investigators

• Study Chair: Eric K. Rowinsky, MD; San Antonio Cancer Institute

• PRS Account: The University of Texas Health Science Center at San Antonio
• Verification Date: June 2012