Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors

University of Arizona

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Gastric Cancer

Esophageal Cancer

Lung Cancer

Ovarian Cancer

Head and Neck Cancer

Prostate Cancer

Treatments

Drug: Taxotere (Docetaxel)

Drug: Alimta (Pemetrexed)

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01172028

05-0108-04

P30CA023074 (U.S. NIH Grant/Contract)

LILLY-UARIZ-05-0108-01 (Other Identifier)

UARIZ-HSC0529 (Other Identifier)

UARIZ-SRC17855 (Other Identifier)

UARIZ-05-0108-01 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells of by stopping them from dividing. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of giving pemetrexed disodium and docetaxel together in treating patients with advanced solid tumors.

Full description

OBJECTIVES:

Primary

To determine the maximum-tolerated dose of the combination of pemetrexed disodium and docetaxel when administered on a day 1 and day 15 dosing schedule.

Secondary

To specifically characterize the toxicity profile for the combination of biweekly pemetrexed disodium and docetaxel.
To investigate the antitumor activity in patients with advanced solid tumors as measured by RECIST criteria for patients with measurable disease or tumor markers for patients with non-measurable disease.
To determine the recommended phase II dose of the combination of pemetrexed disodium and docetaxel on a biweekly dosing schedule.

OUTLINE: This is a dose-escalation study.

Patients receive pemetrexed disodium IV over 10 minutes and docetaxel IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Enrollment

33 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of advanced or recurrent solid tumors
- Patients for whom docetaxel is considered appropriate anticancer therapy; docetaxel is currently approved for use in patients with the following solid tumors:
  - Non-small cell lung (NSCLC)
  - Breast
  - Prostate
  - Esophageal
  - Head and neck
  - Ovarian
  - Gastric
Measurable or non-measurable disease
No squamous cell NSCLC
Controlled brain metastases allowed
- Clinically stable with no signs of progression by MRI or CAT scan ≥ 60 days after treatment
- Patients must be asymptomatic with no steroid requirements

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy ≥ 12 weeks
WBC ≥ 3,000/mm^3*
ANC ≥ 1,500/mm^3*
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/mm^3
Total bilirubin normal
AST, ALT, and alkaline phosphatase (AP) must meet one of the following criteria:
- AST or ALT ≤ 3** times upper limit of normal (ULN) AND AP normal
- AST or ALT ≤ 1.5 times ULN AND AP ≤ 2.5 times ULN
- AST or ALT normal AND AP ≤ 5 times ULN
Calculated creatinine clearance ≥ 45 mL/min OR GFR measured by Tc99m-DPTA serum clearance method
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
Able to interrupt aspirin or other NSAIDs pre- and post- twice-monthly drug dosing
Able to take folic acid, vitamin B12, or corticosteroids
No uncontrolled serious active infections
No pre-existing peripheral neuropathy > grade 1
No significant cardiac disease (i.e., uncontrolled high blood pressure, unstable angina, congestive heart failure within the past 6 months, LVEF < normal, myocardial infarction within the past year, or serious cardiac arrhythmias requiring medication)
No known severe hypersensitivity reaction to docetaxel or other drugs formulated in polysorbate 80 NOTE: *No concurrent colony-stimulating factors to maintain these values

NOTE: **For patients with liver metastases, AST or ALT ≤ 5 times ULN AND AP normal

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Have received 0-1 prior systemic therapy regimens (prior adjuvant chemotherapy will be considered a prior systemic therapy regimen)
At least 4 weeks since prior systemic anticancer therapy (6 weeks for mitomycin C and nitrosoureas)
At least 2 weeks since prior radiotherapy and recovered from the side effects to ≤ grade 1
At least 2 weeks since prior pleurodesis
No concurrent radiotherapy