Paclitaxel, Folic Acid, and Lometrexol in Treating Patients With Locally Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00024310
Recruitment Status : Unknown
Verified November 2002 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : June 20, 2003
Last Update Posted : September 17, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Folic acid may protect normal cells from the side effects of chemotherapy and may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drug. Lometrexol may stop the growth of tumors by blocking one of the enzymes necessary for cancer cell growth. Combining chemotherapy with folic acid and lometrexol may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining paclitaxel, folic acid, and lometrexol in treating patients who have locally advanced or metastatic solid tumors.

Condition or disease Intervention/treatment Phase
Drug/Agent Toxicity by Tissue/Organ Unspecified Adult Solid Tumor, Protocol Specific Dietary Supplement: folic acid Drug: lometrexol Drug: paclitaxel Phase 1

Detailed Description:


  • Determine the maximum tolerated dose and recommended phase II study dose of lometrexol and paclitaxel when combined with folic acid in patients with locally advanced or metastatic solid tumors.
  • Determine the quantitative and qualitative toxic effects of this regimen in these patients.
  • Determine the plasma concentrations of lometrexol and paclitaxel and relate their pharmacokinetics to toxicity outcome in these patients.
  • Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of lometrexol and paclitaxel.

Patients receive lometrexol IV over 30-60 seconds immediately followed by paclitaxel IV over 3 hours on day 1. Patients also receive oral folic acid beginning 7 days before lometrexol/paclitaxel and continuing for 14 days. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Doses of lometrexol and paclitaxel are escalated sequentially. Cohorts of 3-6 patients receive escalating doses of lometrexol and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. Six to twelve additional patients are treated at the recommended phase II study dose (dose immediately preceding the MTD).

Patients are followed every 3 months.

PROJECTED ACCRUAL: Approximately 12-42 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Lometrexol Sodium and Paclitaxel Adminsitered Intravenously Every 21 Days in Conjunction With Oral Folic Acid in Patients With Solid Tumors
Study Start Date : September 2001

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically proven locally advanced or metastatic solid tumor that is refractory to standard therapies or for which there are no therapies of potential major benefit
  • Measurable disease
  • No hematologic malignancies, including leukemia, lymphoma, or multiple myeloma
  • No symptomatic effusions or ascites unless drained before study entry
  • No clinically apparent CNS metastases or carcinomatous meningitis



  • 18 and over

Performance status:

  • WHO 0-1

Life expectancy:

  • At least 12 weeks


  • Absolute neutrophil count at least 1,500/mm^3*
  • Platelet count at least 100,000/mm^3*
  • Hemoglobin at least 9.0 g/dL* NOTE: * Without growth factor support


  • Bilirubin no greater than 2.0 mg/dL
  • SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if tumor involvement of liver)
  • Albumin greater than 2.5 g/dL


  • Glomerular filtration rate at least 65 mL/min


  • No inflammatory bowel disease
  • No radiation enteritis
  • No malabsorption syndrome


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known hypersensitivity to study drugs or related compounds (e.g., LY309887, multi-targeted antifolate, AG-2034, methotrexate, docetaxel, or polyoxyethylated castor oil)
  • No active uncontrolled infection unless approved by the investigator
  • No other severe concurrent disease that would preclude study therapy
  • No body surface area greater than 3.0 m^2
  • No known vitamin B12 deficiency


Biologic therapy:

  • No concurrent routine or prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
  • No concurrent biologic-response modifiers


  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, carboplatin, or nitrosourea) and recovered
  • No other concurrent cytotoxic chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy


  • Recovered from prior radiotherapy
  • No prior radiotherapy to 25% or more of bone marrow (e.g., whole-pelvic irradiation)
  • No concurrent radiotherapy (including palliative radiotherapy)


  • At least 4 weeks since prior major surgery and recovered


  • At least 4 weeks since prior investigational agent
  • No more than 2 prior therapies for locally advanced or metastatic solid tumor
  • No other concurrent investigational agent
  • No concurrent trimethoprim, co-trimoxazole, proguanil, or pyrimethamine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00024310

United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Lee S. Rosen, MD Jonsson Comprehensive Cancer Center Identifier: NCT00024310     History of Changes
Other Study ID Numbers: CDR0000068917
First Posted: June 20, 2003    Key Record Dates
Last Update Posted: September 17, 2013
Last Verified: November 2002

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific
drug/agent toxicity by tissue/organ

Additional relevant MeSH terms:
Albumin-Bound Paclitaxel
Folic Acid
Vitamin B Complex
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Folic Acid Antagonists
Enzyme Inhibitors