Pemetrexed and Oxaliplatin in Treating Patients With Metastatic Solid Tumors or Lymphoma

Vanderbilt University Medical Center

Status and phase

Completed

Phase 1

Conditions

Solid Tumor

Lymphoma

Treatments

Drug: pemetrexed disodium

Drug: oxaliplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00470405

VU-VICC-PHI-0367

VICC PHI0367

VU-IRB-031027

LILLY-H3E-US-S053A

Details and patient eligibility

About

RATIONALE: Pemetrexed may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with oxaliplatin may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of pemetrexed given together with oxaliplatin in treating patients with metastatic solid tumors or lymphoma.

Full description

OBJECTIVES:

Primary

Determine the maximum tolerated dose and the recommended phase II dose of pemetrexed disodium in combination with oxaliplatin in patients with metastatic solid tumors or lymphoma.

Secondary

Determine the quantitative and qualitative toxicities of this regimen in these patients.
Determine, preliminarily, the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive pemetrexed disodium IV over 10 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of pemetrexed disodium and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, the recommended phase II dose will be identified.

After completion of study treatment, patients are followed at 30 days and then periodically thereafter.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pathologic or cytologic diagnosis of solid tumors or lymphoma
Metastatic disease
- No curative or effective therapy exists
Measurable or nonmeasurable disease
No clinically relevant third-space fluid collections
- Fluid collections must be drained before study enrollment
No leukemia
No CNS metastases

Exclusion criteria

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 9 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 3.0 times ULN (5 times ULN if liver has tumor involvement)
Creatinine clearance ≥ 45 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study therapy
No active infection or other serious illness that would preclude study participation
No weight loss ≥ 10% within the past 6 weeks
No peripheral neuropathy (e.g., diabetic neuropathy) ≥ CTC grade 1
Must be able to take concurrent vitamin B12 and folic acid

PRIOR CONCURRENT THERAPY:

No more than 1 prior chemotherapy regimen for metastatic disease
More than 12 months since prior adjuvant therapy
More than 30 days since prior drug that has not received regulatory approval
More than 30 days since prior radiation therapy and recovered (alopecia allowed)
Prior standard postoperative adjuvant radiation therapy for rectal cancer allowed
No prior radiation therapy to ≥ 25% of bone marrow
No prior oxaliplatin or pemetrexed disodium
No NSAIDs or acetylsalicylic acid 2 days before (5 days for long-acting agents [e.g., piroxicam]), during, and for 2 days after each dose of pemetrexed disodium
No concurrent nonpalliative radiation therapy or surgery for cancer
No concurrent hormonal cancer therapy (except medroxyprogesterone)
No other concurrent experimental medications (except thymidine)
No other concurrent chemotherapy or immunotherapy
No other concurrent anticancer therapy
Concurrent palliative radiation therapy allowed for small areas of painful metastasis that cannot be managed adequately by systemic or local analgesics