Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCollin Blakely
About this trial
This phase I/Ib trial studies the side effects and best dose of alisertib when given together with osimertinib in treating patients with EGFR-mutated stage IV lung cancer. Alisertib may stop the growth of tumor cells by blocking a specific protein (Aurora Kinase A) that researchers believe may be important for the growth of lung cancer. Osimertinib may reduce tumor growth by blocking the action of a certain mutant protein (EGFR). This study may help researchers test the safety of alisertib at different dose levels in combination with osimertinib, and to find out what effects, good and/or bad, it has on EGFR-mutated lung cancer.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients must have histologically confirmed stage IV non-small cell lung cancer.
Male or female patients >=18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
Documented activating EGFR mutation (Exon 19 deletion, Exon 19 insertion, E709K, G719X, S768I, V769L, T790M, L833F, L833V, V834L, H835L, L858R, A859S, K860I, L861Q, A871E, V843I, or H870R) on tumor sample or cell-free DNA sample performed in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.
Disqualifiers
Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
Prior allogeneic bone marrow or organ transplantation
Known Gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib. Examples include, but are not limited to partial gastrectomy, history of small intestine surgery, and celiac disease
Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to alisertib.
Trial design
Design model
Sequential
Treatments tested in this trial
Osimertinib
DrugOsimertinib is a medication used to treat non-small-cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor. Patients will be receiving full dose osimertinib (80 mg PO daily) as part of the patient's current standard of care.
Alisertib
DrugAlisertib is an orally available selective aurora A kinase inhibitor. Alisertib will be administered to eligible patients in combination with osimertinib at doses ranging from 20 mg to 50 mg PO twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle. The starting alisertib dose for Cohort 1 will be 30 mg twice daily (dose level 1).
Treatment groups
38 Participants
are divided into 4 treatment groupsGroup A: Dose Escalation (Closed to Enrollment)Experimental treatment 2 interventions
Group B: Dose Expansion: Cohort AExperimental treatment 2 interventions
Group C: Dose Expansion: Cohort BExperimental treatment 2 interventions
Group D: Dose Expansion: Cohort CExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Determination of Maximum Tolerated Dose (MTD) (Cohort A)
The MTD is the highest dose at which no more than one instance of a dose-limiting toxicity is observed among the 6 participants treated.
Time frame
First 28 days of study treatment (1 cycle is 28 days)2
Proportion of patients experiencing dose limiting toxicity (DLT) (Cohort A)
Less than or at least 1 out of 6 at highest dose level below the maximal administered dose. If 0 of these 3 additional participants experience a dose limiting toxicity (DLT) (1 of 6), proceed to the next dose level. If 1 or more of the 3 additional participants experience DLT (2 of 6), then dose escalation is stopped, and this dose is declared the maximal administered dose (highest dose administered). Three (3) additional participants will be entered at the next lowest dose level if only 3 participants were treated previously at that dose.
Time frame
First 28 days of study treatment (1 cycle is 28 days)3
Proportion of patients experiencing serious adverse event (SAE)
The proportion of participants experiencing an adverse event classified as an SAE will be reported by grade and type according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, with exact 95% confidence intervals
Time frame
Up to 2 yearsSecondary outcomes
1
Overall Response Rate (ORR)
The ORR is defined as the best overall response recorded from the start of the treatment until disease progression from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined based on RECIST 1.1 criteria. We will compute a 95% confidence interval using a binomial distribution.
Time frame
Up to 2 years2
Median Duration of Response (DR)
The DR for CR and PR will be measured from the date that the best response if first recorded until the date that PD is documented over the period of 2 years. For patients who continue treatment post-progression, the date of PD documentation will be used for analysis. The DR will be summarized using descriptive statistics.
Time frame
Up to 2 years3
Percentage of tumor shrinkage
The depth of response (DOR) will be assessed by RECIST 1.1 criteria. DOR is defined as the percentage of tumor shrinkage, based on longest diameter or reconstructed volume, observed at the lowest point (nadir) compared with baseline. The DOR will be summarized using descriptive statistics
Time frame
Up to 2 years4
Disease Control Rate (DCR)
Defined as the percentage of patients who have achieved CR, PR, or SD (based on RECIST 1.1 criteria) for at least 12 weeks. The DCR will be summarized using descriptive statistics.
Time frame
Up to 2 yearsSponsors and contacts
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Collin Blakely
Lead sponsor
University of California, San Francisco
Sponsor institution
Puma Biotechnology, Inc.
Collaborator
Source ClinicalTrials.gov