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

• ClinicalTrials.gov Identifier: NCT00470405
• Recruitment Status: Completed
• First Posted: May 7, 2007
• Last Update Posted: April 18, 2011
• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Vanderbilt-Ingram Cancer Center

Tracking Information

• First Submitted Date: May 3, 2007
• First Posted Date: May 7, 2007
• Last Update Posted Date: April 18, 2011
• Study Start Date: May 2004
• Actual Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2007)

• Maximum tolerated dose
• Recommended phase II dose

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 3, 2007)

• Toxicity
• Efficacy

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pemetrexed and Oxaliplatin in Treating Patients With Metastatic Solid Tumors or Lymphoma
• Official Title: A Phase I Study of ALIMTA Plus Oxaliplatin Administered Every Other Week in the Treatment of Patients With Metastatic Cancer

Brief Summary

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.

Detailed 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.

• 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

• Lymphoma
• Solid Tumor

Intervention

• Drug: oxaliplatin
  75-100 mg/m2 iv infusion Approximately 2 hours beginning approximately 30 minutes after the end of ALIMTA infusion on Day 1 of a 14-days cycle
  Other Name: Elaxtin
• Drug: pemetrexed disodium
  a novel antifolate with multiple targets.

Study Arms

Experimental: Therapeutic Intervention

Interventions:

• Drug: oxaliplatin
• Drug: pemetrexed disodium

• Publications *: Stover DG, Lockhart AC, Berlin JD, Chan E, Sandler AB, Sosman JA, Middlebrook V, Nicol S, Rothenberg ML. Phase I trial of pemetrexed plus oxaliplatin administered every other week in patients with metastatic cancer. Invest New Drugs. 2008 Aug;26(4):339-45. doi: 10.1007/s10637-008-9133-4. Epub 2008 May 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 13, 2010): 25
• Original Enrollment (submitted: May 3, 2007): 36
• Actual Study Completion Date: November 2007
• Actual Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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: NCT00470405
• Other Study ID Numbers: VICC PHI0367; VU-VICC-PHI-0367; LILLY-H3E-US-S053A; VU-IRB-031027
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mace Rothenberg, Vanderbilt-Ingram Cancer Center
• Study Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mace L. Rothenberg, MD, FACP; Vanderbilt-Ingram Cancer Center

• PRS Account: Vanderbilt-Ingram Cancer Center
• Verification Date: April 2011