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

Primary Purpose

Lymphoma, Solid Tumor

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
oxaliplatin
pemetrexed disodium
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring adult solid tumor, unspecified adult solid tumor, protocol specific, stage IV adult Hodgkin lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous B-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, adult nasal type extranodal NK/T-cell lymphoma, adult grade III lymphomatoid granulomatosis, Waldenstrom macroglobulinemia, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, nodal marginal zone B-cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, splenic marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic Intervention

Arm Description

Outcomes

Primary Outcome Measures

Maximum tolerated dose
Recommended phase II dose

Secondary Outcome Measures

Toxicity
Efficacy

Full Information

First Posted
May 3, 2007
Last Updated
April 14, 2011
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00470405
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
May 2007 (Actual)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Solid Tumor
Keywords
adult solid tumor, unspecified adult solid tumor, protocol specific, stage IV adult Hodgkin lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous B-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, adult nasal type extranodal NK/T-cell lymphoma, adult grade III lymphomatoid granulomatosis, Waldenstrom macroglobulinemia, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, nodal marginal zone B-cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, splenic marginal zone lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic Intervention
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
Elaxtin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Intervention Description
a novel antifolate with multiple targets.
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Title
Recommended phase II dose
Secondary Outcome Measure Information:
Title
Toxicity
Title
Efficacy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mace L. Rothenberg, MD, FACP
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18463792
Citation
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.
Results Reference
result

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

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