Phase 2 Trial of Alisertib (MLN8237) in Combination With Paclitaxel Versus Placebo in Combination With Paclitaxel as Second Line Therapy for Small Cell Lung Cancer (SCLC)
- Conditions
- Relapsed or Refractory Small cell lung cancerMedDRA version: 18.0Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003713-18-CZ
- Lead Sponsor
- Millennium Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 166
1. Male or female patients = 18 years old.
2. Have a pathologically (histology or cytology) confirmed diagnosis of
SCLC. Patients with mixed or combined small cell and non-small cell
histology tumors are eligible.
3. Have received and progressed after a platinum based standard chemotherapy regimen for first line treatment of SCLC, either limited stage (LS) or extensive stage (ES). Patients could not have received any prior second-line therapy for relapsed or progressive disease, including re-treatment with original frontline regimen. Patients should have relapsed within < 180 days after their last administration of platinum chemotherapy. At least 3 weeks should have elapsed between the end of first line therapy and the first dose of study drug. No previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression.
4. Have measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) within = 2 weeks before randomization. Clear radiographic evidence of disease progression after initial therapy should have been documented.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0 1).
6. Patients with treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed, provided the lesions have been stable for at least 2 weeks and the patient is off steroids or is on a stable dose of steroids. Patients should be without neurologic dysfunction that would confound the evaluation of neurological and/or other AEs. Patients with brain metastases should not require use of enzyme-inducing antiepileptic drugs (eg, carbamazepine, phenytoin, or phenobarbital) within 14 days before first dose and during study. Use of newer antiepileptics that do not produce enzyme induction drug-drug interactions (DDIs) is allowed. Radiotherapy must have been completed a minimum of 14 days prior to randomization, and patients must have recovered from AEs related to the radiotherapy to < grade 1 (except alopecia).
7. Patients requiring full systemic anticoagulation are eligible if they have tolerated treatment with a stable dose and schedule without bleeding complications for more than 1 month.
8. Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
• Adhere to any treatment-specific pregnancy prevention guidelines for
paclitaxel.
Male patients, even if surgically sterilized (ie, status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
• Adhere t
1. Any prior therapy for second-line treatment of SCLC.
2. Patients who relapsed = 180 days after their last administration of
platinum therapy.
3. Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib in any setting or any other investigational agent in the relapsed setting.
4. Prior treatment with paclitaxel or any other taxane agent.
5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components.
6. Any comorbid condition or unresolved toxicity that would preclude administration of alisertib or weekly paclitaxel.
7. Prior history of = Grade 2 neurotoxicity that is not resolved to = Grade 1.
8. Patients with symptomatic and/or progressive brain metastases or with carcinomatous meningitis.
9. Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of alisertib and during study conduct. Major prohibited enzyme inducers include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, and St. John’s wort.
10. Inability to swallow alisertib or other orally administered medications.
11. Requirement for administration of proton pump inhibitor (PPI), H2
antagonist, or pancreatic enzymes. Use of any PPI in either continued or
intermittent use will be prohibited during the conduct of the study and
patients must discontinue any use of PPI within 5 days prior to the first
dose of alisertib.
12. Diagnosed with or treated for another malignancy within 3 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present.
13. Other severe acute or chronic medical or psychiatric condition(s), including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
14. Uncontrolled cardiovascular conditions, including but limited to
symptomatic ischemic heart disease, angina, cardiac arrhythmias, active
conduction system abnormalities, congestive heart failure (CHF) or
hypertension despite appropriate medical therapy. Chronic stable atrial
fibrillation on stable anticoagulant therapy is allowed. Patients with a
pacemaker may be enrolled in the study upon discussion with the project
clinician.
15. Thromboembolic events (eg, deep vein thrombosis, pulmonary
embolism, or symptomatic cerebrovascular events) within 6 months
before receiving the first dose of study drug.
16.Known history of human immunodeficiency virus (HIV) infection,
hepatitis B or hepatitis C. Testing is not required in the absence of
clinical findings or suspicion. Patients with prior allogeneic bone
marrow or organ transplantation or with an active condition of chronic
immune suppression are not eligible.
17. Infection requiring IV antibiotic therapy or other serious infection
within 14 days before the first dose of study drug.
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method