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

Phase 1/Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

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



- 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)


- 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
I. 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.

Inclusion Criteria


- 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

- No history of CNS disease, including primary brain tumor, seizures, or carcinomatous


- 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

- No serious uncontrolled, concurrent medical illness, including ongoing or active

- 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

- No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to prostate-specific antigen (PSA) and objective progression

Safety Issue:


Principal Investigator

Eric J. Small, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Federal Government

Study ID:




Start Date:

February 2005

Completion Date:

September 2006

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • Prostatic Neoplasms



UCSF Comprehensive Cancer CenterSan Francisco, California  94115