Clinical trial NCT00470405: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-05-07
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose
measure: Recommended phase II dose
Secondary outcomes:
measure: Toxicity
measure: Efficacy
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Mace L. Rothenberg, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References:
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.