A Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

NCT01094288 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C14009
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of alisertib in combination with docetaxel as a treatment for participants with advanced solid tumors, including castration-resistant prostate cancer, who were deemed by the investigator to be medically appropriate candidates for docetaxel therapy.

Conditions

Advanced Solid Tumors; Adenocarcinoma of the Prostate

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)

Secondary Outcomes (13)

• Cmax: Maximum Observed Plasma Concentration for Docetaxel

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

• AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

• AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

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

  Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2

• Cmax: Maximum Observed Plasma Concentration for Alisertib

  Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1

Study Arms (1)

Alisertib + Docetaxel

EXPERIMENTAL

Alisertib in escalating dose (10-40 mg), enteric-coated tablets (ECT), orally, twice daily for 7 days followed by 14-day rest period in Cycle 1, 3 and onwards (21-day cycle) and orally twice daily from Day 3 to Day 7 followed by 14 day rest period in Cycle 2 along with docetaxel 60-75 mg/m\^2, intravenous (IV) infusion on Day 1 of each cycle for maximum of 12 months, or until the occurrence of progressive disease (PD), unmanageable adverse events (AEs) or withdrawal of consent. The starting alisertib dose is 10 mg, orally, twice daily (total 20 mg/day).

Drug: Alisertib; Drug: Docetaxel

Interventions

Alisertib DRUG

Alisertib ECT

Also known as: MLN8237

Alisertib + Docetaxel

Docetaxel DRUG

Docetaxel IV infusion

Alisertib + Docetaxel

Eligibility Criteria

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

You may qualify if:

• years or older
• Histologically or cytologically confirmed advanced tumors and candidates for docetaxel treatment
• Measurable or evaluable disease is required. Participants must have clinical evidence of progressive disease or persistent disease
• Participants with castration-resistant prostate cancer (CRPC) are required to have
• Pathologically confirmed adenocarcinoma of the prostate
• Evidence of metastatic disease on bone scan or other imaging. Participants with prostate-specific antigen (PSA) elevation as the only manifestation of disease are not eligible.
• Progressive disease after at least 1 hormonal treatment with documented testosterone levels less than 50 ng/dl
• Concurrent use of an agent for testosterone suppression (e.g., luteinizing hormone-releasing hormone \[LHRH\] agonist) is required if the participants has not been surgically castrated
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Recovered to less than or equal to Grade 1 toxicity (CTCAE), to participant's baseline status (except alopecia) or deemed irreversible from the effects of prior cancer therapy and must have evidence of progressive or persistent disease
• Adequate bone marrow, liver and renal function
• Any use of opiates must be stable for at least 2 weeks prior to study entry
• Female participants who are postmenopausal for at least 1 year OR are surgically sterile OR if of childbearing potential, agree to practice 2 effective methods of contraception at the same time
• Male participants who agree to practice effective barrier contraception during the entire study and through 6 months after the last dose of study drug OR agree to abstain from heterosexual intercourse
• Voluntary written consent

You may not qualify if:

• Female participants who are lactating or pregnant
• Antineoplastic therapy or any experimental therapy within 21 days before the first dose of alisertib
• Prior or current investigational therapies within 4 weeks before the first dose of MLN8237
• Concurrent investigational treatment of treatment with any investigational products within 28 days before the first dose of alisertib
• Radiotherapy to greater than 40% of bone marrow or any radiotherapy (except localized, small field radiation) within 4 weeks prior to enrollment, unless reviewed and approved by the medical monitor
• Nitrosoureas or mitomycin-C within 6 weeks before the first dose of alisertib.
• Autologous stem cell transplant within 3 months before the first dose of alisetib, or prior allogeneic stem cell transplant at any time.
• Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of alisertib
• For CRPC participants:
• Radiotherapy or antiandrogen therapy for prostate cancer within 4 weeks prior to enrollment
• Prior treatment with antineoplastic chemotherapy or radioisotopes for advanced prostate cancer
• Use of products known to affect PSA levels within 4 weeks of enrollment
• Major surgery within 4 weeks of study enrollment
• Uncontrolled high blood pressure
• Participants with abnormal gastric or bowel function or who require continuous treatment with antacids or proton pump inhibitors

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (4)

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

MeSH Terms

Interventions

MLN 8237; Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2010
• First Posted: March 26, 2010
• Study Start: August 17, 2010
• Primary Completion: February 28, 2014
• Study Completion: January 4, 2017
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-10

Locations

US (4)