Clinical trial NCT01094288: A Phase 1 Study of Alisertib Participants With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen
Official title: A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Adenocarcinoma of the Prostate
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-03-26
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors including castration-resistant prostate cancer.

The study enrolled approximately 41 patients. Participants were enrolled to receive:

• Alisertib 10-40 mg + docetaxel 60-75 mg/m\^2

All participants will receive alisertib (ECT) in dose escalating cohorts, 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 \[dose held for pharmacokinetic (PK) collection\] along with docetaxel 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 AEs or withdrawal of consent.

This multi-center trial is conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. Participants made multiple visits to the clinic, and were contacted every 12 weeks for up to 25.8 months after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

* 18 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
* Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
* Suitable venous access for blood sampling

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

* 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
* Participants receiving chronic steroid therapy other than the following: low dose steroid for the control of nausea and vomiting, topical steroid, inhaled steroid or use of dexamethasone
* Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate 80
* Comorbid condition or unresolved toxicity that would preclude administration of docetaxel
* Prior history of Grade 2 or greater neurotoxicity or any toxicity that has not resolved to Grade 1 or below
* Symptomatic brain or other CNS metastasis
* 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
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
* Participants requiring full systemic anticoagulation
* Prior allogeneic bone marrow or other organ transplant
* Active infection requiring systemic therapy within 14 days preceding first dose, or other serious infection
* History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
* Serious medical or psychiatric illness that could interfere with protocol completion
* Inability to swallow oral medication
* Prior treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens
* Prior treatment with more than 1 prior taxane-containing regimen

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Docetaxel
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
measure: AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
measure: AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
measure: Terminal Phase Elimination Half-life (T1/2) for Docetaxel
timeFrame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
measure: Cmax: Maximum Observed Plasma Concentration for Alisertib
timeFrame: 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
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib
timeFrame: 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
measure: AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib
timeFrame: 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
measure: Overall Response Rate (ORR) Assessed for Overall Participant Population
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
measure: Overall Response Rate for Prostate Cancer Participants
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
measure: Best Overall Response Rate Assessed by RECIST Criteria
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
measure: Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
measure: Duration of Response
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
measure: Duration of Stable Disease (SD)
timeFrame: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
Other outcomes:
Locations:
city: Indianapolis
country: United States
state: Indiana
city: Portland
country: United States
state: Oregon
city: San Antonio
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: