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

NCT01084655 | Completed Phase 1 Results

• 1 other identifier: C21003
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (4)

• Phase 2: Time to PSA Progression

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

• Phase 2: Time to Radiographic Disease Progression

  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

  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)

  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)

Study Arms (3)

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone

EXPERIMENTAL

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; Drug: Docetaxel; Drug: Prednisone

Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone

EXPERIMENTAL

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; Drug: Docetaxel; Drug: Prednisone

Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

EXPERIMENTAL

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; Drug: Docetaxel; Drug: Prednisone

Interventions

TAK-700 DRUG

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

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone; Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone; Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Docetaxel DRUG

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

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone; Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone; Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Prednisone DRUG

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

Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone; Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone; Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (1)

Alaska Clinical Research Center, LLC

Anchorage, Alaska, 99508, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

orteronel; Docetaxel; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2010
• First Posted: March 10, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: March 1, 2016
• Last Updated: July 30, 2019
• Results First Posted: July 30, 2019

Record last verified: 2019-07

Locations

US (1)