A Phase I/II Study of Docetaxel/Prednisone and PTK 787/ZK 222584 in Previously Untreated Metastatic Hormone Refractory Prostate Cancer
A Phase I/II Study of Docetaxel/Prednisone and PTK 787/ZK 222584 in Previously Untreated Metastatic Hormone Refractory Prostate Cancer
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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a phase I open-label, dose-escalation study of vatalanib* followed by a phase II study.
NOTE: *Vatalanib is administered on days 5-21 during the first course only.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 93 patients will be accrued for this study.
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
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
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
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
No psychiatric illness or social situation that would limit compliance with treatment
No "currently active" second malignancy other than nonmelanoma skin cancers
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 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
No other concurrent hormonal therapy except for the following: