Phase 2 N=24 Randomized Treatment

Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

Advanced Nonhematological Malignancies · Non-Small Cell Lung Cancer · Small Cell Lung Cancer · Metastatic Breast Cancer · Head and Neck Squamous Cell Carcinoma

Bottom Line

View on ClinicalTrials.gov: NCT01045421 ↗

Enrolled (actual)

Serious AEs

44.7%

Results posted

Aug 2016

Primary outcome: Primary: Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs) — 0; 0; 0; 2 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: MLN8237 (Alisertib) (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Millennium Pharmaceuticals, Inc.
Primary completion: May 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)	0; 0; 0; 2; 0; 0	—
PRIMARY Phase 2: Percentage of Participants With Objective Response	18; 9; 9; 4; 21	—
SECONDARY Phase 2: Progression-free Survival (PFS)	164; 49; 72; 92; 49	—
SECONDARY Phase 2: Time to Disease Progression (TTP)	164; 46; 72; 92; 78	—
SECONDARY Phase 2: Duration of Response (DOR)	169; 198; 79; NA; 125	—
SECONDARY Phase 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events and Serious Adverse Events	52; 52; 54; 26; 57; 23	—
SECONDARY Phase 1: Cmax- Maximum Observed Plasma Concentration for Alisertib	297; 602; 949; 1619; 1696; 981	—
SECONDARY Phase 1: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib	2.9; 2.0; 3.2; 2.2; 6.0; 3.1	—
SECONDARY Phase 1: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib	2640; 3495; 5015; 10736; 13932; 8660	—
SECONDARY Phase 1: Terminal Phase Elimination Half-life (T1/2) for Alisertib	20.6; 16.0; 19.0; 20.8; 27.8	—
SECONDARY Phase 1: Rac- Accumulation Ratio for Alisertib	3.3; 3.0; 2.3; 2.2; 2.4	—
SECONDARY Phase 1: Peak to Trough Ratio for Alisertib	1.7; 2.1; 2.3; 2.3; 1.8	—
SECONDARY Phase 1: Steady State Oral Clearance (CLss/F) for Alisertib	2.2; 3.8; 5.6; 4.6; 4.0	—
SECONDARY Phase 2: Relationship Between Clinical Response and Molecular Markers of Response	0; NA; 23; NA; 65; NA	—

Summary

This is an open-label, multicenter study with a phase 1 dose escalation portion and a 2-stage, phase 2 portion, investigating MLN8237 (alisertib) in patients with advanced nonhematological malignancies.

Eligibility Criteria

Inclusion Criteria

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

18 years or older
Histologically or cytologically confirmed metastatic and/or advanced solid tumor (Phase 1 only)
Phase 2 requires Non-small cell lung cancer (NSCLC); Small-cell lung cancer; Breast adenocarcinoma (female patients only); Squamous cell cancer of the head and neck (HNSCC); or Gastroesophageal adenocarcinoma
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
Voluntary written consent
Wiling to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
Measurable disease (Phase 2 only)

Exclusion Criteria

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

Female patients who are pregnant or lactating
Serious medical or psychiatric illness that could interfere with protocol completion
Receipt of more than 2 previous cytotoxic chemotherapeutic regimens (4 previous regimens for breast cancer). There is no limit on the number of prior noncytotoxic therapies
Prior treatment with Aurora A-targeted agents, including MLN8237
Prior treatment with high-dose chemotherapy
Prior allogeneic bone marrow or other organ transplant
Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of MLN8237
Symptomatic brain metastasis
Radiotherapy to greater than 25% of bone marrow
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
Myocardial infarction within 6 months of enrollment
Uncontrolled cardiovascular condition
Major surgery within 14 days of first dose of MLN8237
Active infection requiring systemic therapy, or other serious infection
Inability to swallow oral medication
Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
Patients requiring full systemic anticoagulation
History of uncontrolled sleep apnea syndrome
Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 and during the study

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01045421). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.