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

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

TAK-700

Docetaxel

Prednisone

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept 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

Sites / Locations

Alaska Clinical Research Center, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone

Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone

Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Arm 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.

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.

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).

Outcomes

Primary Outcome Measures

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE)

Number of Participants With TEAEs Related to Hematology and Serum Chemistry

Number of Participants With TEAEs Related to Vital Signs

Number of Participants With TEAEs Related to Electrocardiogram (ECG)

Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel

Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel

Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel

Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel

Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State 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

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.

Phase 2: Best PSA Response

Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT01084655

First Posted

March 9, 2010

Last Updated

July 9, 2019

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01084655

Brief Title

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

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Completed

Study Start Date

July 2010 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone

Arm Type

Experimental

Arm Description

Arm Title

Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone

Arm Type

Experimental

Arm Description

Arm Title

Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TAK-700

Intervention Description

TAK-700 with docetaxel and prednisone on a continuous schedule.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Intervention Description

TAK-700 with docetaxel and prednisone on a continuous schedule.

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

TAK-700 with docetaxel and prednisone on a continuous schedule.

Primary Outcome Measure Information:

Title

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE)

Time Frame

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)

Title

Number of Participants With TEAEs Related to Hematology and Serum Chemistry

Time Frame

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)

Title

Number of Participants With TEAEs Related to Vital Signs

Time Frame

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)

Title

Number of Participants With TEAEs Related to Electrocardiogram (ECG)

Time Frame

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)

Title

Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel

Time Frame

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

Title

Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel

Time Frame

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

Title

Phase 2: AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Docetaxel

Time Frame

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

Title

Phase 2: Terminal Phase Elimination Half-life (T1/2) for Docetaxel

Time Frame

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

Title

Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel

Time Frame

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

Title

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

Time Frame

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

Title

Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90%

Description

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.

Time Frame

Cycle 4 Day 21

Title

Phase 2: Best PSA Response

Description

Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1.

Time Frame

Cycle 2 Day 1 up to Cycle 12 Day 21

Secondary Outcome Measure Information:

Title

Phase 2: Time to PSA Progression

Description

Time Frame

Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Title

Phase 2: Time to Radiographic Disease Progression

Description

Time Frame

Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Title

Phase 2: Percentage of Participants With Objective Measurable Disease Response

Description

Time Frame

Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)

Title

Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs)

Description

Baseline is defined as the last scheduled observed measurement prior to the first dose of drug.

Time Frame

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)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Millennium Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Alaska Clinical Research Center, LLC

City

Anchorage

State/Province

Alaska

ZIP/Postal Code

99508

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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