Docetaxel, Prednisone, and Vatalanib in Treating Patients With Advanced Prostate Cancer

Sponsor

University of California, San Francisco (Other)

Overall Status

Terminated

CT.gov ID

NCT00293371

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving vatalanib together with docetaxel and prednisone may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vatalanib when given together with docetaxel and prednisone and to see how well they work in treating patients with advanced prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: docetaxel Drug: prednisone Drug: vatalanib	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the dose-limiting toxicities and maximum tolerated dose of vatalanib when used in combination with docetaxel and prednisone in patients with chemotherapy-naive, metastatic, hormone-refractory prostate cancer. (phase I)

Secondary

Determine alterations in pharmacokinetics of docetaxel and vatalanib in these patients. (phase I)
Determine the clinical efficacy of this regimen as measured by declines in prostate-specific antigen, measurable disease response, time to progression, and overall survival. (phase II)

OUTLINE: This is a phase I open-label, dose-escalation study of vatalanib* followed by a phase II study.

Phase I: Patients receive docetaxel IV over 1 hour on day 2. Patients also receive oral prednisone twice daily and oral vatalanib once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of vatalanib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

NOTE: *Vatalanib is administered on days 5-21 during the first course only.

Phase II: Patients receive prednisone, docetaxel, and vatalanib at the MTD as in phase

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 93 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Docetaxel/Prednisone and PTK 787/ZK 222584 in Previously Untreated Metastatic Hormone Refractory Prostate Cancer

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Sep 1, 2006

Actual Study Completion Date :

Sep 1, 2006

Outcome Measures

Primary Outcome Measures

Time to prostate-specific antigen (PSA) and objective progression []
Response rate (PSA and objective) []
Toxicity []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically documented adenocarcinoma of the prostate
Progressive, systemic (metastatic) disease despite castrate levels of testosterone due to orchiectomy or luteinizing-hormone releasing hormone (LHRH) agonist, meeting 1 of the following criteria:
Measurable disease, defined as any lesion that can be accurately measured in at least 1 dimension ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan or MRI
Nonmeasurable disease with PSA ≥ 5 ng/mL
Bone lesions
Pleural or pericardial effusions, ascites
CNS lesions, leptomeningeal disease
Irradiated lesions, unless progression documented after radiotherapy
No PSA ≥ 5 ng/mL as only evidence of disease
PSA evidence for progressive prostate cancer consists of a PSA level ≥ 5 ng/mL that has risen on ≥ 2 successive occasions, ≥ 2 weeks apart
Castrate levels of testosterone (< 50 ng/dL) must be maintained
If no prior orchiectomy, patients must remain on testicular androgen suppression (e.g., with an LHRH analogue)
Patients receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression after discontinuation of antiandrogen
Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression
For patients receiving flutamide or megestrol acetate, at least 1 of the PSA values must be obtained 4 weeks or more after flutamide/megestrol acetate discontinuation
For patients receiving bicalutamide or nilutamide, at least 1 of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation
If improvement after antiandrogen withdrawal is noted, disease progression must be established
No pleural effusion or ascites that causes respiratory compromise ( ≥ grade 2 dyspnea)
No history of CNS disease, including primary brain tumor, seizures, or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Fertile patients must use effective barrier contraception during and for 3 months after completion of study treatment
Karnofsky performance status ≥ 60%
Life expectancy > 12 weeks
Granulocyte count > 1,500/mm^3
Platelet count > 75,000/mm^3
Hemoglobin > 8.0 g/dL
Creatinine < 1.5 times upper limit of normal (ULN)
Bilirubin < 1.5 times ULN
SGOT/SGPT < 1.5 times ULN
Urinalysis ≤ 1+ proteinuria based on dipstick reading OR 2+ proteinuria on dipstick reading AND total urinary protein ≤ 3,500 mg on 24 hour urine collection and creatinine clearance ≥ 50 mL/min on a 24-hour urine collection
No impairment of gastrointestinal (GI) function or GI disease that may affect or alter absorption of vatalanib (i.e., malabsorption syndromes)
No myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (New York Heart Association class III or IV), or uncontrolled cardiac arrhythmia
No pre-existing grade 3 or 4 clinical peripheral neuropathy
No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
No deep vein thrombosis or pulmonary embolus within the past year
No poorly controlled diabetes (fasting blood glucose > 250) despite optimization of medical therapy
No labile or poorly controlled hypertension (systolic blood pressure > 160 mm Hg, diastolic blood pressure > 90 mm Hg) despite maximal management with anti-hypertensives
No serious uncontrolled, concurrent medical illness, including ongoing or active infection
Patients on Suppressive antibiotic therapy for chronic urinary tract infection are eligible
No psychiatric illness or social situation that would limit compliance with treatment
No "currently active" second malignancy other than nonmelanoma skin cancers
Not considered "currently active" if competed therapy and at < 30% risk of relapse
No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No grapefruit or grapefruit juice during study treatment
No history of gastrectomy/small bowel resection
At least 4 weeks since prior hormonal therapy, including ketoconazole, aminoglutethimide, systemic steroids (any dose), and megestrol acetate (any dose)
At least 4 weeks since prior drug or herbal product known to decrease PSA levels (e.g., finasteride, saw palmetto, or PC-SPES)
At least 4 weeks since prior major surgery and fully recovered
At least 4 weeks since prior radiation therapy and fully recovered
At least 8 weeks since the last dose of prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
Patients receiving bisphosphonate therapy prior to initiating protocol treatment must have received bisphosphonates for at least the past month
No bisphosphonate initiation for 1 month prior to and during study treatment
No prior systemic chemotherapy for prostate cancer
No prior antiangiogenic agents (thalidomide, bevacizumab)
No other concurrent chemotherapy, investigational agents, radiotherapy (including palliative), or biologic therapy
No biologic therapy or immunotherapy ≤ 4 weeks prior to study treatment
No more than 1 prior therapy with an investigational agent, completed ≥ 4 weeks prior to study treatment
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent therapeutic warfarin or similar oral anticoagulant that is metabolized by the cytochrome p450 system
Heparin is allowed
No other concurrent hormonal therapy except for the following:
Steroids for adrenal failure
Hormones for nondisease-related conditions (e.g., insulin for diabetes)
Intermittent dexamethasone