Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

Phase I Dose Escalation Trial of Biweekly Alimta (With Vitamin Supplementation) in Combination With Taxotere in Advanced Solid Tumor Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172028
• Other study ID #: 05-0108-04
• Secondary ID: P30CA023074UARIZ
• Status: Completed
• Phase: Phase 1
• First received: July 28, 2010
• Last updated: December 2, 2015
• Start date: September 2005
• Est. completion date: July 2014

Study information

• Verified date: February 2014
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Esophageal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer
• Ovarian Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• Taxotere (Docetaxel)
Taxotere is a third generation cytotoxic chemotherapy agent which is a semisynthetic taxane that inhibits cell division by promoting the rate of microtubule assembly and preventing microtubule depolymerization. It has broad antitumor activity in a range of solid tumors, and has been studied on a weekly as well as a biweekly dosing schedule.
• Alimta (Pemetrexed)
ALIMTA is a novel antifolate drug with three enzyme targets in the purine and pyrimidine synthetic pathway. It has broad activity in solid tumors and has been combined with a number of other chemotherapy agents. Its toxicity is modified by the use of continuous vitamin supplementation.

Locations

Country	Name	City	State
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
University of Arizona	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose (MTD) of combination ALIMTA and Taxotere		From first dose of the study drug until 30 days after the last administration of study medication	Yes
Secondary	Toxicity		From first dose of the study drug until 30 days after the last administration of study medication	Yes
Secondary	Antitumor activity		From first dose of the study drug until 30 days after the last administration of study medication	No