A Phase I-III, Multicenter Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Patients With Resectable Stage I-III Non-Small Cell Lung Cancer, Selected According to Biomarker Status
Overview
- Phase
- Phase 3
- Intervention
- Alectinib
- Conditions
- Not specified
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 11
- Locations
- 22
- Primary Endpoint
- Cohort B1: Incidence, type, and severity of adverse events (AEs) with onset up to 28 days after the last dose of chemotherapy
- Status
- Active, Not Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The objective of this study is to evaluate the efficacy and/or safety of multiple therapies in patients with early-stage resectable NSCLC. Cohort B1 is a phase II cohort that will evaluate the safety, and efficacy of alectinib in combination with up to four cycles of platinum-based chemotherapy in the adjuvant setting post complete surgical resection. Cohort B2 is a phase II cohort that will evaluate the efficacy and safety of perioperative alectinib in combination with chemotherapy in the neoadjuvant setting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Complete resection of the primary NSCLC with negative margins
- •Confirmed stage II to select stage IIIB (T3N2) NSCLC of non-squamous (adenocarcinoma) histology
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Inclusion Criteria Cohort B2:
- •Evaluation by the operating attending surgeon and involved medical oncologist prior to study enrollment to verify study eligibility for complete surgical resection with curative intent
- •Pathologically and/or histologically confirmed Stage II-IIIA and IIIB (T3N2 only) NSCLC of non-squamous (adenocarcinoma) histology
- •Inclusion Criteria Cohorts B1 and B2:
- •Documented ALK fusion
Exclusion Criteria
- •NSCLC of squamous or mixed histology regardless of the presence of an ALK mutation
- •Prior exposure to any systemic anti-cancer therapy
- •Exclusion Criteria Cohort B2:
- •NSCLC of squamous or mixed histology regardless of the presence of an ALK mutation
- •Known sensitivity to any component of alectinib, pemetrexed, cisplatin, or carboplatin
- •Prior exposure to any systemic anti-cancer therapy
- •Exclusion Criteria Cohorts B1 and B2:
- •Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Arms & Interventions
Cohort B1
Participants will receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 5 years.
Intervention: Alectinib
Cohort B1
Participants will receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 5 years.
Intervention: Cisplatin
Cohort B1
Participants will receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 5 years.
Intervention: Carboplatin
Cohort B1
Participants will receive alectinib in combination with platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 5 years.
Intervention: Pemetrexed
Cohort B2
Participants will receive alectinib and platinum-based chemotherapy for up to 3 cycles (cycle length = 3 weeks) prior to surgery, and alectinib monotherapy after surgery for up to 5 years after surgery.
Intervention: Alectinib
Cohort B2
Participants will receive alectinib and platinum-based chemotherapy for up to 3 cycles (cycle length = 3 weeks) prior to surgery, and alectinib monotherapy after surgery for up to 5 years after surgery.
Intervention: Cisplatin
Cohort B2
Participants will receive alectinib and platinum-based chemotherapy for up to 3 cycles (cycle length = 3 weeks) prior to surgery, and alectinib monotherapy after surgery for up to 5 years after surgery.
Intervention: Carboplatin
Cohort B2
Participants will receive alectinib and platinum-based chemotherapy for up to 3 cycles (cycle length = 3 weeks) prior to surgery, and alectinib monotherapy after surgery for up to 5 years after surgery.
Intervention: Pemetrexed
Outcomes
Primary Outcomes
Cohort B1: Incidence, type, and severity of adverse events (AEs) with onset up to 28 days after the last dose of chemotherapy
Time Frame: Up to 28 days after the last dose of chemotherapy treatment (up to 4 cycles, cycle length = 3 weeks)
Cohort B2: Investigator-assessed pathologic complete response (inv-pCR)
Time Frame: At the time of surgical resection (approximately weeks 14-17)
Secondary Outcomes
- Cohort B1: Investigator-assessed disease-free survival (DFS)(From initiation of study treatment to the first documented recurrence of disease or new primary NSCLC or death from any cause, whichever occurs first (up to approximately 5 years))
- Cohort B1: Overall survival (OS)(From initiation of study treatment to death from any cause (up to approximately 8 years))
- Cohort B1: Incidence, type, and severity of AEs with onset up to 28 days after the last dose of study treatment(From first dose to up to approximately 5 years)
- Cohort B2: Investigator-assessed overall response rate (ORR)(Up to approximately Week 17)
- Cohort B2: Investigator-assessed event-free survival (EFS)(From first treatment to the first documented disease progression that prevents surgery, local or distant disease recurrence, or death from any cause (up to approximately 5 years))
- Cohort B1: Time to first onset of selected AEs(From first dose to up to approximately 5 years)
- Cohort B1: Change from baseline in target safety parameters(From first dose to up to approximately 5 years)
- Cohort B2: Investigator-assessed major pathological response (inv-MPR)(At the time of surgical resection (approximately weeks 14-17))
- Cohort B2: Pathologic complete response (pCR) by independent review(At the time of surgical resection (approximately weeks 14-17))
- Cohort B2: Major pathologic response (MPR) by independent review(At the time of surgical resection (approximately weeks 14-17))
- Cohort B2: Overall Survival (OS)(From initiation of study treatment to death from any cause (up to approximately 8 years))
- Cohort B2: Incidence, severity, and type of AEs(From first dose up to approximately 5 years)
- Cohort B2: Change from baseline in target safety parameters(From first dose to up to approximately 5 years)
- Cohort B2: Frequency of surgery completion, defined as participants who have successfully completed surgery without treatment-related delays (> 60 days) from the last dose of neoadjuvant treatment(At the time of surgical resection (approximately weeks 14-17))
- Cohort B2: Length of treatment-related surgical delays, incidence of operative and post-operative complications, and/or reasons for surgical cancellations(Approximately weeks 14-24)