Clinical trial NCT01084655: Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer
Official title: An Open-label Phase 1/2 Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-10
Enrollment: 38
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE)
timeFrame: 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)
measure: Number of Participants With TEAEs Related to Hematology and Serum Chemistry
timeFrame: 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)
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: 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)
measure: Number of Participants With TEAEs Related to Electrocardiogram (ECG)
timeFrame: 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)
measure: Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel
timeFrame: 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
measure: Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
timeFrame: 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
measure: Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel
timeFrame: 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
measure: Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel
timeFrame: 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
measure: Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel
timeFrame: 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
measure: 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
timeFrame: 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
measure: Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90%
timeFrame: Cycle 4 Day 21
measure: Phase 2: Best PSA Response
timeFrame: Cycle 2 Day 1 up to Cycle 12 Day 21
Secondary outcomes:
measure: Phase 2: Time to PSA Progression
timeFrame: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
measure: Phase 2: Time to Radiographic Disease Progression
timeFrame: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
measure: Phase 2: Percentage of Participants With Objective Measurable Disease Response
timeFrame: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
measure: Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs)
timeFrame: 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)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, LLC
state: Alaska
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: