Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer

Millennium Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: Prednisone; Drug: Docetaxel; Drug: TAK-700

Study type: Interventional

Funder types: Industry

Identifiers

NCT01084655

C21003

Details and patient eligibility

About

This is an open-label, multicenter, Phase 1/2 study of TAK-700 in combination with docetaxel and prednisone that will evaluate the safety and pharmacokinetics (PK) of the combination and will allow estimation of prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer (mCRPC).

Enrollment: 38 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Each patient must meet all of the following inclusion criteria:

• Voluntary written consent
• Male patients 18 years or older
• Estimated life expectancy of 6 months or more
• Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
• Radiograph-documented metastatic disease
• Progressive disease
• Prior surgical castration or concurrent use of an agent for medical castration
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Physical examination findings that are consistent with other study entry or exclusion criteria and identified but not excluded chronic conditions
• Even if surgically sterilized, patients must Practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug, OR Abstain from heterosexual intercourse
• Any use of opiates must be stable for at least 2 weeks prior to study entry
• Meet screening laboratory values as specified in protocol
• Suitable venous access

Exclusion criteria

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Known hypersensitivity to TAK-700, docetaxel, prednisone or related compounds
• Received any of the following within 30 days prior to the first dose of TAK-700: prior therapy with any investigational compound; prior herbal product known to decrease PSA; OR radiation therapy for prostate cancer
• Received prior therapy with TAK-700, aminoglutethimide, ketoconazole or abiraterone (for Phase 1 only, patients previously treated with ketoconazole or abiraterone will be eligible if treatment with ketoconazole or abiraterone was discontinued at least 30 days prior to enrollment)
• Received antiandrogen therapy within 4 weeks for flutamide and 6 weeks for all others prior to first dose of study drug
• Received prior chemotherapy for prostate cancer
• Current spinal cord compression, bilateral hydronephrosis or neck outlet obstruction
• Symptoms that investigator deems related to prostate cancer
• Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
• Uncontrolled cardiovascular condition
• New York Heart Association Class (NYHA) Class III or IV
• Uncontrolled hypertension despite medical therapy
• Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
• Unwilling or unable to comply with protocol
• Major surgery or serious infection within 14 days of first dose of TAK-700
• Life-threatening illness unrelated to cancer
• Uncontrolled nausea, vomiting or diarrhea
• Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of TAK-700

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 3 patient groups

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone

Experimental group

Description:

Orteronel (TAK-700) 200 milligram (mg), tablets, orally, twice daily (BID) starting from Day 1 along with docetaxel 75 milligram per square meter (mg/m\^2), infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods.

Treatment:

Drug: TAK-700

Drug: Prednisone

Drug: Docetaxel

Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone

Experimental group

Description:

Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Day 1 along with docetaxel 75 mg/m\^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets , orally, twice daily from Day 8 up to Day 21 of each treatment cycle. Cycle 1 of Phase 1 consisted of a 28-day treatment period and subsequent cycles consisted of 21-day treatment periods.

Treatment:

Drug: TAK-700

Drug: Prednisone

Drug: Docetaxel

Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Experimental group

Description:

Orteronel (TAK-700) 400 mg, tablets, orally, twice daily starting from Cycle 1 Day 15 along with docetaxel 75 mg/m\^2, infusion, intravenously over 1 hour on Day 1 and prednisone 5 mg, tablets, orally, twice daily from Day 1 up to Day 21 of each 21-day treatment cycle until disease progression or end of treatment (EOT).

Treatment:

Drug: TAK-700

Drug: Prednisone

Drug: Docetaxel