Know Cancer

or
forgot password

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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Drug/Agent Toxicity by Tissue/Organ, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

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


OBJECTIVES:

- 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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- WHO 0-1

Life expectancy:

- At least 12 weeks

Hematopoietic:

- 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

Hepatic:

- 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

Renal:

- Glomerular filtration rate at least 65 mL/min

Gastrointestinal:

- No inflammatory bowel disease

- No radiation enteritis

- No malabsorption syndrome

Other:

- 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

- No concurrent biologic-response modifiers

Chemotherapy:

- 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

Radiotherapy:

- 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)

Surgery:

- At least 4 weeks since prior major surgery and recovered

Other:

- 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Lee S. Rosen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000068917

NCT ID:

NCT00024310

Start Date:

September 2001

Completion Date:

Related Keywords:

  • Drug/Agent Toxicity by Tissue/Organ
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • drug/agent toxicity by tissue/organ
  • Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781