Clinical trial NCT01172028: Pemetrexed Disodium and Docetaxel in Treating Patients With Advanced Solid Tumors
Official title: Phase I Dose Escalation Trial of Biweekly Alimta (With Vitamin Supplementation) in Combination With Taxotere in Advanced Solid Tumor Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Esophageal Cancer
Gastric Cancer
Head and Neck Cancer
Lung Cancer
Ovarian Cancer
Prostate Cancer
Keywords: 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
stage IV lymphoepithelioma of the oropharynx
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
stage III esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage III inverted papilloma of the paranasal sinus and nasal cavity
stage III midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
stage III salivary gland cancer
stage IV salivary gland cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent ovarian germ cell tumor
stage III gastric cancer
stage IV gastric cancer
recurrent gastric cancer
recurrent hypopharyngeal cancer
stage III hypopharyngeal cancer
stage IV hypopharyngeal cancer
recurrent laryngeal cancer
stage III laryngeal cancer
stage IV laryngeal cancer
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-07-29
Enrollment: 33
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: 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.

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.

Eligibility 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

Primary outcomes:
measure: Maximum-tolerated dose (MTD) of combination ALIMTA and Taxotere
timeFrame: From first dose of the study drug until 30 days after the last administration of study medication
Secondary outcomes:
measure: Toxicity
timeFrame: From first dose of the study drug until 30 days after the last administration of study medication
measure: Antitumor activity
timeFrame: From first dose of the study drug until 30 days after the last administration of study medication
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
Study officials:
affiliation: University of Arizona
name: Lee Cranmer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: