Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer

NCT00439270 | Completed Phase 1 Results

• 1 other identifier: CA180-086
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to find the recommended doses of dasatinib and docetaxel given in combination to men with metastatic hormone refractory prostate cancer and to assess the pharmacokinetic interactions between the 2 drugs.

Conditions

Metastatic Prostate Cancer

Keywords

Metastatic hormone refractory prostate cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel

  MTD was defined by dose-limiting toxicity (DLT) criteria. DLT was defined as grade 4 neutropenia causing treatment interruption for \>14 days, febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with a bleeding episode requiring platelet transfusion, nausea and/or vomiting despite medical intervention/prophylaxis causing treatment interruption for \>14 days, grade 3-4 asthenia/fatigue, any other grade \>=3 nonhematologic toxicity except alopecia or transient arthralgia/myalgia (unless unresponsive to intervention), or interruption of study drug for \>14 days due to toxicity. When defined, the MTD would serve as recommended Phase 2 dose of each drug in the combination of oral dasatinib and intravenous docetaxel.

  From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)

• Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2

  Because no dose-limiting toxicities occurred, the recommended dose of dasatinib used in Phase 2 was based on findings from ongoing studies in chronic myelogenous leukemia and experience from the previous Phase 2 study of single-agent dasatinib in chronic refractory prostate cancer. The recommended Phase 2 dose of docetaxel (75 mg/m\^2) was based on the docetaxel package insert.

  From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)

Secondary Outcomes (14)

• Percentage of Participants With a Prostate Specific Antigen (PSA) Response

  At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment (up to 51.6 months)

• Duration of Prostate Specific Antigen (PSA) Response

  At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment

• Number of Months of Progression-free Survival (PFS)

  Patients with an event: time from first dose to disease progression or death, whichever occurs first. Patients without an event: time to last on-study PSA measurement, tumor assessment, or radionuclide bone scan assessment, whichever occurs last

• Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

  Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)

• Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

  Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)

Study Arms (5)

Dasatinib, 50 mg + Docetaxel, 60 mg/m^2

ACTIVE COMPARATOR

Participants received dasatinib, 50 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 60 mg/m\^2.

Drug: Dasatinib; Drug: Docetaxel

Dasatinib, 50 mg + Doxetaxel, 75 mg/m^2

ACTIVE COMPARATOR

Participants received dasatinib, 50 mg administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Drug: Dasatinib; Drug: Docetaxel

Dasatinib, 70 mg + Docetaxel, 75 mg/m^2

ACTIVE COMPARATOR

Participants received dasatinib, 70 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Drug: Dasatinib; Drug: Docetaxel

Dasatinib, 100 mg + Docetaxel, 75 mg/m^2

ACTIVE COMPARATOR

Participants received dasatinib, 100 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Drug: Dasatinib; Drug: Docetaxel

Dasatinib, 120 mg + Docetaxel, 75 mg/m^2

ACTIVE COMPARATOR

Participants received dasatinib, 120 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Drug: Dasatinib; Drug: Docetaxel

Interventions

Dasatinib DRUG

Tablets, Oral, 50, 70, 100, or 120 mg once daily; treatment may continue until disease progression

Also known as: Sprycel, BMS-354825

Dasatinib, 100 mg + Docetaxel, 75 mg/m^2; Dasatinib, 120 mg + Docetaxel, 75 mg/m^2; Dasatinib, 50 mg + Docetaxel, 60 mg/m^2; Dasatinib, 50 mg + Doxetaxel, 75 mg/m^2; Dasatinib, 70 mg + Docetaxel, 75 mg/m^2

Docetaxel DRUG

Infusion, 60 or 75 mg/m\^2, administered every 3 weeks.

Dasatinib, 100 mg + Docetaxel, 75 mg/m^2; Dasatinib, 120 mg + Docetaxel, 75 mg/m^2; Dasatinib, 50 mg + Docetaxel, 60 mg/m^2; Dasatinib, 50 mg + Doxetaxel, 75 mg/m^2; Dasatinib, 70 mg + Docetaxel, 75 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate that was clinically refractory to hormone therapy
• Eastern Cooperative Oncology Group performance status of 0 - 2
• Evidence of progressive metastatic disease at time of enrollment
• Measurable disease on either computer tomography scan or magnetic resonance imaging or positive bone scan with any level of serum prostate specific antigen (PSA) ≥5 ng/ml. Patients with PSA ≥5 ng/ml only and no other radiographic evidence of metastatic prostate cancer were not eligible
• Evidence of progressive disease since the most recent change in therapy. Progressive disease was defined as any one of the following:
• Objective disease progression: Objective evidence of increase in radiographic lesions or the appearance of 1 or more new lesions
• Bone scan progression: Appearance of either of the following: 2 or more new lesions on bone scan attributable to prostate cancer or 1 new lesion on bone scan attributable to prostate cancer in conjunction with a rising PSA
• PSA progression: 2 consecutively rising PSA levels (≥5 ng/mL) separated by 2 weeks with a testosterone concentration of ≤50 ng/dL at 2 week intervals
• Serum testosterone levels ≤50 ng/dL, determined within 2 weeks prior to starting treatment
• Maintaining castrate status: patients who had not undergone surgical orchiectomy must have continued on medical therapies, such as gonadotropin-releasing hormone analogs, to maintain castrate levels of serum testosterone. Those receiving an antiandrogen as part of their first-line hormonal therapy must have shown progression of disease off of the antiandrogen prior to enrollment (6 weeks withdrawal for bicalutamide; 4 weeks for flutamide)

You may not qualify if:

• Sexually active fertile men not using effective birth control if their partners were women of child-bearing potential
• Known brain metastases
• Clinically-significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months; prolonged heart rate-corrected QT interval (QTc) \>450 msec; ejection fraction \<40%, or major conduction abnormality (unless a cardiac pacemaker was present)
• Pleural or pericardial effusion, due to concerns that the combination of docetaxel and dasatinib could worsen these events
• Uncontrolled intercurrent illness including, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that limit compliance with study requirements
• Participants were permitted to continue on a daily multivitamin but all other herbal, alternative, and food supplements must have been discontinued before enrollment into the study
• Ketoconazole must have been discontinued 4 weeks prior to enrollment
• Patients were not permitted to receive radioactive bone targeting agents, such as Strontium or Samarian ,while on study treatment
• The following restrictions on prior therapy for metastatic disease applied:
• One chemotherapy regimen was permitted as long as docetaxel resistance or intolerance was not demonstrated. Docetaxel resistance was defined as objective disease progression or confirmed PSA progression during docetaxel therapy or within 3 months of treatment completion. Docetaxel intolerance was defined as toxicity requiring docetaxel interruption \>4 weeks or dose modification below approved doses
• No more than 1 prior course of palliative radiotherapy
• Up to 1 prior treatment with a nonchemotherapeutic agent was permitted as treatment for metastatic prostate cancer
• No prior radioisotope therapy with Strontium-89, Samarium, or similar agents
• No limitation on prior hormonal therapy
• QTc prolonging agents strongly associated with Torsade de Pointes arrhythmia

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (5)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Springfield Clinic

Springfield, Illinois, 62703, United States

Location

Hematology-Oncology Associates Of Rockland

Nyack, New York, 10960, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

The University Of Texas Md Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Related Publications (1)

• Araujo JC, Mathew P, Armstrong AJ, Braud EL, Posadas E, Lonberg M, Gallick GE, Trudel GC, Paliwal P, Agrawal S, Logothetis CJ. Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1-2 study. Cancer. 2012 Jan 1;118(1):63-71. doi: 10.1002/cncr.26204. Epub 2011 Jul 25.

  PMID: 21976132 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dasatinib; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2007
• First Posted: February 23, 2007
• Study Start: July 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: January 1, 2013
• Last Updated: March 28, 2014
• Results First Posted: November 27, 2013

Record last verified: 2014-02

Locations

US (5)