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Study Summary
No. 2007-0067:.......Prostate......John Araujo......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
2007-0067
Study Title:Phase I/II Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer (CA180086)
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Physician New Patient Referral
Name:John AraujoPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Genitourinary Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2830
Contact us about clinical trials
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General Information
Disease Group:ProstateSupported By:Bristol-Myers Squibb
Phase of Study:Phase I/Phase IIReturn
Visit:
Participants will be required to return to clinic every 3 weeks for docetaxel
administration and evaluation.
Treatment
Agents:
Dasatinib
Docetaxel
Home Care:Participants are responsible for taking oral dasatinib once daily.
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of the Phase I portion of this clinical research study is to find the
highest tolerable doses of Sprycel™ (dasatinib) and TaxotereŽ (docetaxel) that
can be given in combination with prednisone, in patients with prostate cancer
that has spread.

The goal of the Phase II portion of this clinical research study is to learn
how the study drugs (dasatinib, docetaxel, and prednisone) affect each other in
the body. The safety and effectiveness of this combination treatment will also
be studied.
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Study Objectives / Outcomes
Primary Objectives:

Phase I: The primary objective for the Phase I portion of the study is to define using clinical safety observations and pharmacokinetics the maximum tolerated dose (MTD) and recommended Phase II dose of each drug in the combination of oral dasatinib and intravenous docetaxel in subjects with metastatic hormone-refractory prostate cancer (HRPC).

Phase II: The primary objective for the Phase II portion of the study is to assess whether there is drug-drug pharmacokinetic interaction at the recommended Phase II dose for the combination of intravenous docetaxel and oral dasatinib.
    Secondary Objectives:

    Phase I: The secondary objectives for the Phase I portion of the study include:
      • Pharmacokinetic assessment of each drug and the combination of docetaxel and dasatinib
      • Describe changes in serum PSA levels, bone scans, and tumor size in escalating dose cohorts of the combination of docetaxel and dasatinib
      • Assess safety and tolerability in escalating dose cohorts of the combination treatment of dasatinib and docetaxel.

    Phase II: The secondary objectives for the Phase II portion of the study include:
      • Assess safety and tolerability of dasatinib and docetaxel in combination at the recommended Phase II dose determined in Phase I
      • Estimates of efficacy
        • Estimate rate and duration of PSA response
        • Estimate progression free survival
        • Estimate objective response rate
        • Describe bone scan changes
        • Estimate subject-reported changes in pain intensity using the Brief Pain Inventory - short form (BPI-sf).
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    Study Status Information
    Study Activation / Registration Date:
    IRB Review and Approval Date:06/29/2007
    Study Type:Phase Ii Or Phase I/Ii
    Recruitment Status:Closed
    Projected Accrual:N/A
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    Enrollment Eligibility
    If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

    Inclusion Criteria:1) Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.

    2) Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate that is clinically refractory to hormone therapy.

    3) ECOG Performance Status 0 - 2.

    4) At the time of enrollment, patients must have evidence of progressive metastatic disease. Measurable disease on either CT scan or MRI or positive bone scan with any level of serum PSA >/= 5 ng/ml. Patients with PSA >/= 5 ng/ml only and no other radiographic evidence of metastatic prostate cancer are not eligible.

    5) Patients must have demonstrated evidence of progressive disease (PD) since the most recent change in therapy. PD is defined as any one of the following (objective disease progression, bone scan, or PSA progression): a) Objective Disease Progression: Objective evidence of increase in radiographic lesions or the appearance of one or more new lesions.

    6) (# 5 cont'd) b) Bone Scan Progression: Appearance of either of the following will constitute progression: (a) 2 or more new lesions on bone scan attributable to prostate cancer; or (b) one new lesion on bone scan attributable to prostate cancer in conjunction with a rising PSA.c) PSA Progression: two consecutively rising PSA levels (>/= 5 ng/mL) separated by two weeks with a testosterone concentration of </= 50 ng/mL at two week intervals.

    7) Serum testosterone </= 50 ng/mL, determined within two weeks prior to starting treatment.

    8) Maintaining castrate status: Patients who have not undergone surgical orchiectomy should continue on medical therapies [e.g. gonadotropin releasing hormone analogs (GnRH analogs)] to maintain castrate levels of serum testosterone. Patients who are receiving an anti-androgen as part of their first-line hormonal therapy must have shown progression of disease off of the anti-androgen prior to enrollment (6 weeks withdrawal for bicalutamide; 4 weeks for flutamide).

    9) At least four weeks since major surgery.

    10) Required Initial Laboratory Data: a) WBC >/= 3,000/mm^3. b) ANC >/= 1,500/mm^3. c) Platelet count >/= 100,000/mm^3. d) Creatinine </= 1.5 x upper limits of normal. e) Bilirubin </= upper limit of normal (exceptions will be made for patients with Gilbert's Disease). f) SGOT (AST) </= 2.5 x upper limits of normal. g) SGPT (ALT) </= 2.5 x upper limits of normal.

    11) If obese, a patient must be treated with doses of docetaxel calculated using his actual body surface area (BSA) (The physician must be comfortable treating at the full BSA dose).

    12) Men only, at least 18 years old.

    Exclusion Criteria:1) Sexually active fertile men not using effective birth control if their partners are WOCBP. Taxanes are considered to be teratogenic. For this reason men whose sexual partners are of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of study participation. Should a patient's sexual partner become pregnant or suspect she is pregnant while patient is participating in this study, the treating physician should be informed immediately.

    2) Patients with known brain metastases are excluded from this clinical trial.

    3) Clinically-significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc > 450 msec., Ejection Fraction (EF) < 40% or major conduction abnormality (unless a cardiac pacemaker is present).

    4) Patients with a pleural or pericardial effusion will be excluded from this clinical trial as the combination of docetaxel and dasatinib may worsen this condition.

    5) Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be enrolled into the study. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse.

    6) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    7) Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with docetaxel.

    8) History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents.

    9) Patients may not be receiving any other investigational agents for the treatment of prostate cancer.

    10) Patients may continue on a daily Multi-Vitamin but all other herbal, alternative and food supplements (i.e. PC-Spes, Saw Palmetto, St John Wort, etc.) must be discontinued before enrollment into the study.

    11) Ketoconazole must be discontinued 4 weeks prior to enrollment.

    12) Patients on stable doses of bisphosphonates, who develop subsequent tumor progression, may continue on this medication. However patients are not allowed to initiate bisphosphonate therapy immediately prior to or during the study, to avoid risk of hypocalcemia and confounding of bone effects by the simultaneous introduction of two new agents affecting bone.

    13) Patients must not receive radioactive bone targeting agents such as Strontium or Samarian while on this protocol.

    14) The following restrictions on prior therapy for metastatic disease apply: a) One chemotherapy regimen will be permitted, as long as docetaxel resistance or intolerance was not demonstrated. Docetaxel resistance is defined as objective disease progression or confirmed PSA progression during docetaxel therapy or within 3 months of treatment completion. Docetaxel intolerance is defined as toxicity requiring docetaxel interruption greater than 4 weeks or dose modification below approved doses. b) No more than one prior course of palliative radiotherapy.

    15) (# 14 cont'd) c) Up to one prior treatment with a non-chemotherapeutic agent (e.g., kinase inhibitors, immunotherapeutic agents, etc) is permitted as treatment for metastatic prostate cancer. d) No prior radioisotope therapy with Strontium-89, Samarium or similar agents. e) No limitation on prior hormonal therapy.

    16) Potent CYP 3A4 inhibitors and inducers or QTc prolonging agents strongly associated with Torsade de Pointes arrhythmia.

    17) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this study.

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    Links
    Registration Number: NCT00439270
    Study Information on Clinical Trials Registry (clinicaltrials.gov)

    Other Links:
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    Results


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