alisertib in adults with nonhematological malignancies, followed by alisertib in lung, breast, head and neck or gastroesophageal malignancies

Conditions: Advanced Nonhematological Malignancies; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Metastatic Breast Cancer; Head and Neck Squamous Cell Carcinoma; Gastroesophageal Adenocarcinoma

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.

following the determination of the recommended phase 2 dose (rp2d) and schedule (phase 1), 20 response-evaluable patients in each of the 5 tumor indications will be enrolled (phase 2-stage 1). an interim analysis will determine which tumor indications will proceed to enroll an additional 25 patients (phase 2-stage 2) to further evaluate overall response rate (orr) and other secondary endpoints.

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

Keywords: nsclc sclc hnscc