Randomized Study Comparing Docetaxel Plus Dasatinib to Docetaxel Plus Placebo in Castration-resistant Prostate Cancer (READY)

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Prostatic Neoplasms

Treatments: Drug: Prednisone; Drug: Dasatinib; Drug: Docetaxel; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00744497

2008-000701-11 (EudraCT Number)

CA180-227

Details and patient eligibility

About

The purpose of this study is to determine whether survival can be prolonged in patients with castration-resistant prostate cancer who receive dasatinib with docetaxel and prednisone.

Enrollment: 1,930 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• History of histologically diagnosed prostate cancer
• Evidence of metastatic disease by any 1 of the following: computed tomography scan, magnetic resonance imaging, bone scan, or skeletal survey
• Evidence of progression, as defined by 1 of the following: rising prostate specific antigen levels at least 1 week apart with the final value being >=2 ng/mL; progression of measurable nodal or visceral disease, with nodal lesions >=20 mm and visceral lesions measurable per response evaluation criteria for solid tumors (Response Evaluation in Solid Tumors, version 1); 2 or more lesions appearing on bone scan compared with previous scan; or local recurrence in the prostate or prostate bed
• Maintaining castrate status: Participants who have not undergone surgical orchiectomy should have received and continue on medical therapies, such as gonadotropin releasing hormone analogs, to maintain castrate levels of serum testosterone <=50 ng/dL
• Eastern Cooperative Oncology Group Performance Status of 0 to 2
• At least 4 weeks since an investigational agent prior to starting study therapy
• At least 8 weeks since radioisotope therapy prior to starting study therapy
• Recovery from any local therapy including surgery or radiation/radiotherapy for a minimum of 7 days prior to starting study therapy
• Required initial laboratory values: white blood cell count >=3,000/mm^3; absolute neutrophil count >=1,500/mm^3; platelet count >=100,000/mm^3; creatinine level <=1.5*upper limit of normal (ULN); bilirubin <=ULN; aspartate aminotransferase <=2.5*ULN; alanine aminotransferase <=2.5*ULN.

Exclusion criteria

• Symptomatic brain metastases or leptomeningeal metastases
• Clinically significant cardiovascular disease, including myocardial infarction; ventricular tachyarrhythmia within 6 months; prolonged QTc >450 msec; ejection fraction <40%; or major conduction abnormality, unless a cardiac pacemaker is present
• Pleural or pericardial effusion of any Common Terminology Criteria (CTC) grade
• Peripheral neuropathy CTC Grade >=2
• Currently active second malignancy other than nonmelanoma skin cancers. Participants 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
• Uncontrolled intercurrent illness including ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• HIV infection-positive patients receiving combination antiretroviral therapy
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents
• Receipt of any other investigational agents for the treatment of prostate cancer
• Prior cytotoxic chemotherapy in the metastatic setting, with the exception of estramustine
• Patients may continue on a daily multivitamin but must discontinue all other herbal, alternative, and food supplements before enrollment
• Ketoconazole must be discontinued 4 weeks prior to starting study therapy
• Antiandrogens must be discontinued prior to starting study therapy. Patients with a history of response to an antiandrogen and subsequent progression while on that antiandrogen should be assessed for antiandrogen withdrawal response for 4 weeks. Observation for antiandrogen withdrawal response is not necessary for those who have never responded to antiandrogens
• Bisphosphonates must not be initiated within 28 days prior to starting study therapy
• QT prolonging agents strongly associated with torsade de pointes.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,930 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m\^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Treatment:

Drug: Docetaxel

Drug: Placebo

Drug: Prednisone

Dasatinib

Active Comparator group

Description:

Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m\^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Treatment:

Drug: Docetaxel

Drug: Prednisone

Drug: Dasatinib