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

Study Overview
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Brief Summary
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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).

Official Title
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An Open-label Phase 1/2 Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: TAK-700
* Drug: Docetaxel
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone<br>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. | Drug: TAK-700<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Docetaxel<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Prednisone<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>|
| Experimental: Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone<br>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. | Drug: TAK-700<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Docetaxel<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Prednisone<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>|
| Experimental: Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone<br>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). | Drug: TAK-700<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Docetaxel<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>Drug: Prednisone<br>* TAK-700 with docetaxel and prednisone on a continuous schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE) |  | Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21) | 
| Number of Participants With TEAEs Related to Hematology and Serum Chemistry |  | Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21) | 
| Number of Participants With TEAEs Related to Vital Signs |  | Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21) | 
| Number of Participants With TEAEs Related to Electrocardiogram (ECG) |  | Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21) | 
| Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel |  | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion | 
| Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel |  | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion | 
| Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel |  | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion | 
| Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel |  | Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion | 
| Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel |  | Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel | 
| Phase 2: AUC 0-tau: Area Under the Plasma Concentration Versus Time Curve Zero to the Time of the End of the Dosing Interval for Orteronel |  | Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel | 
| Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90% | PSA response rates (PSA-30, PSA-50, and PSA-90) were defined as greater than or equal to (>=) 30%, 50%, and 90% reductions, respectively, from baseline in PSA concentration. | Cycle 4 Day 21 | 
| Phase 2: Best PSA Response | Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1. | Cycle 2 Day 1 up to Cycle 12 Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2: Time to PSA Progression | Time to PSA progression was defined as (date of PSA progression) - (date of first dose of drug) + 1, where PSA progression was defined as: For participants whose PSA concentrations never declined before the end of Cycle 4 of treatment: a) >=25% increase over the baseline level and an increase in absolute PSA concentration >=2 ng/mL; For participants who initially experienced a PSA decline: a) >=25% increase in PSA above the nadir concentration and an increase in absolute PSA concentration >=2 ng/mL. | Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months) | 
| Phase 2: Time to Radiographic Disease Progression | Time to Radiographic Disease Progression was defined as (date of Radiographic Disease progression) - (date of first dose of drug) + 1. Radiographic disease progression is defined as the presence of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) criteria and/or bone scan progression determined according to second Prostate Cancer Clinical Trials Working Group (PCWG2) bone scan criteria. | Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months) | 
| Phase 2: Percentage of Participants With Objective Measurable Disease Response | Percentage of participants with objective measurable disease response based assessment of complete response (CR), partial response (PR), stable disease or PD according to RECIST (Version 1.1). A CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to less than (<)10 millimeter (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes. | Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months) | 
| Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs) | Baseline is defined as the last scheduled observed measurement prior to the first dose of drug. | Cycle 2 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1, End of treatment (approximately up to Cycle 48), Last assessment (30 days after last dose of study drug, approximately up to 1038 days) |