Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT01172028
• Recruitment Status: Completed
• First Posted: July 29, 2010
• Last Update Posted: December 3, 2015
• Sponsor: University of Arizona
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Arizona

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Esophageal Cancer; Gastric Cancer; Head and Neck Cancer; Lung Cancer; Ovarian Cancer; Prostate Cancer	Drug: Taxotere (Docetaxel); Drug: Alimta (Pemetrexed)	Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Dose Escalation Trial of Biweekly Alimta (With Vitamin Supplementation) in Combination With Taxotere in Advanced Solid Tumor Patients
• Study Start Date: September 2005
• Actual Primary Completion Date: July 2014
• Actual Study Completion Date: July 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: Alimta and Taxotere; Alimta and Taxotere given in combination with dose modifications.

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.; Other Name: Docetaxel; Drug: 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.; Other Name: Pemetrexed

Outcome Measures

Primary Outcome Measures :

1. Maximum-tolerated dose (MTD) of combination ALIMTA and Taxotere [ Time Frame: From first dose of the study drug until 30 days after the last administration of study medication ]

Secondary Outcome Measures :

1. Toxicity [ Time Frame: From first dose of the study drug until 30 days after the last administration of study medication ]
2. Antitumor activity [ Time Frame: From first dose of the study drug until 30 days after the last administration of study medication ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States, 85724-5024

Sponsors and Collaborators

University of Arizona

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lee Cranmer, MD, PhD; University of Arizona

More Information

• Responsible Party: University of Arizona
• ClinicalTrials.gov Identifier: NCT01172028
• Other Study ID Numbers: 05-0108-04; P30CA023074 ( U.S. NIH Grant/Contract ); UARIZ-05-0108-01 ( Other Identifier: University of Arizona ); UARIZ-HSC0529 ( Other Identifier: University of Arizona ); UARIZ-SRC17855 ( Other Identifier: University of Arizona ); LILLY-UARIZ-05-0108-01 ( Other Identifier: University of Arizona )
• First Posted: July 29, 2010
• Last Update Posted: December 3, 2015
• Last Verified: February 2014

Keywords provided by University of Arizona:

stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; male breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; recurrent breast cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer; stage III esophageal cancer; stage IV esophageal cancer; recurrent esophageal cancer; recurrent adenoid cystic carcinoma of the oral cavity; recurrent mucoepidermoid carcinoma of the oral cavity; stage III adenoid cystic carcinoma of the oral cavity; stage III mucoepidermoid carcinoma of the oral cavity; stage IV adenoid cystic carcinoma of the oral cavity; stage IV mucoepidermoid carcinoma of the oral cavity; recurrent basal cell carcinoma of the lip; stage III basal cell carcinoma of the lip; stage IV basal cell carcinoma of the lip; recurrent lymphoepithelioma of the nasopharynx; stage III lymphoepithelioma of the nasopharynx; stage IV lymphoepithelioma of the nasopharynx; recurrent lymphoepithelioma of the oropharynx; stage III lymphoepithelioma of the oropharynx

Additional relevant MeSH terms:

Breast Neoplasms; Lung Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Prostatic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Docetaxel; Pemetrexed; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action