Pemetrexed, Cisplatin, and Radiation Therapy in Treating Patients With Esophageal or Gastroesophageal Junction Cancer

University of Arizona

Status and phase

Completed

Phase 1

Conditions

Esophageal Cancer

Treatments

Radiation: radiation therapy

Drug: Pemetrexed

Drug: cisplatin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00701857

LILLY-UARIZ-07-0612-04 (Other Grant/Funding Number)

UARIZ-BIO07067 (Other Identifier)

P30CA023074 (U.S. NIH Grant/Contract)

UARIZ-SRC18084 (Other Identifier)

UARIZ-07-0612-04 (Other Identifier)

07-0612-04

Details and patient eligibility

About

RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cisplatin may make tumor cells more sensitive to radiation therapy. Giving pemetrexed together with cisplatin and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of pemetrexed when given together with cisplatin and radiation therapy in treating patients with stage III or stage IV esophageal cancer or gastroesophageal junction cancer.

Full description

OBJECTIVES:

Primary

To establish the maximum tolerated dose of pemetrexed disodium in combination with cisplatin and standard-dose radiotherapy in patients with stage III or IV esophageal or gastroesophageal junction carcinoma.

Secondary

To specifically characterize the toxicity profile of this regimen.
To investigate, preliminarily, the anti-tumor activity of this regimen, as measured by standard response criteria (RECIST criteria), in patients with measurable disease.

OUTLINE: This is a dose-escalation study of pemetrexed disodium.

Patients receive pemetrexed disodium IV over 10 minutes on days 1, 15, and 29 and cisplatin IV over 10 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external beam radiotherapy once daily, 5 days a week, for up to 6 weeks.

After completion of study therapy, patients are followed for 30 days and then every 3 months for 1 year.

Enrollment

10 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of esophageal or gastroesophageal junction carcinoma
- Stage III or IV disease
Treatment with chemoradiotherapy is considered appropriate
Measurable or evaluable disease
Clinically significant pleural or pericardial effusions or ascites allowed provided they were drained prior to study entry
- No pleurodesis within the past 2 weeks
Controlled brain metastasis allowed provided patient is clinically stable with no signs of progression by MRI or CT scan of the brain ≥ 60 days after completion of treatment AND is asymptomatic and does not require steroids

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
WBC ≥ 2,500/mm^3
ANC ≥ 1,500/mm^3
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 100,000/mm^3
Total bilirubin normal
Alkaline phosphatase AND AST and ALT meeting the following criteria:
- Alkaline phosphatase normal AND AST or ALT ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastases)
- Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal
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
Able to take folic acid, vitamin B_12, or corticosteroids
No known severe hypersensitivity reaction to study drugs
No uncontrolled serious active infection
No pre-existing peripheral neuropathy > grade 1
No significant cardiac disease, including any of the following:
- Uncontrolled high blood pressure
- Unstable angina
- Congestive heart failure within the past 6 months
- Left ventricular ejection fraction below the lower limit of normal
- Myocardial infarction within the past year
- Serious cardiac arrhythmias requiring medication

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior systemic therapy regimens
No prior radiotherapy to gastric/esophageal fields
No aspirin or other NSAID before and after pemetrexed disodium administration
No concurrent colony-stimulating factors (CSF) to maintain WBC and ANC eligibility values