Phase Ib, Open-label, Multi-center Study of the Combination of Pertuzumab and Erlotinib in Patients With Locally Advanced or Metastatic (Stage IIIb/IV) NSCLC After Failure of at Least One Prior Chemotherapy Regimen.
Overview
- Phase
- Phase 1
- Intervention
- Erlotinib
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 17
- Primary Endpoint
- Percentage of Participants With Dose Limiting Toxicities (DLTs)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This study will assess the safety and tolerability, and make a preliminary assessment of activity, of a combination of pertuzumab and erlotinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have failed on at least one prior chemotherapy regimen. The anticipated time on study treatment is until disease progression or unacceptable toxicity, and the target sample size is less than 100 individuals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult patients greater than or equal to 18 years of age
- •Histological confirmation of non-small cell lung cancer (NSCLC)
- •Locally advanced or metastatic disease
- •Failure of at least one prior regimen of standard chemotherapy for locally advanced or metastatic disease
- •Life expectancy of more than or equal to 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Baseline Left Ventricular Ejection Fraction (LVEF) of greater than or equal to 50%
- •A negative pregnancy test one week prior to treatment and willingness to use contraception among women of childbearing potential
- •Availability of histological Formalin-Fixed, Paraffin-Embedded (FFPE) tumor tissue
Exclusion Criteria
- •Prior chemotherapy, radiotherapy or immunotherapy within 4 weeks of study Day -8
- •Prior treatment with any agent which targets growth factors or their receptors
- •Patients who have not recovered from the acute reversible effects of chemotherapy and radiotherapy
- •History of clinically significant cardiovascular disease
- •History or evidence of central nervous system metastases
- •Treatment with any investigational drug within 28 days of the start of the study (day -8)
- •Prior cumulative doxorubicin dose of more than 360 mg/m2 or the equivalent
Arms & Interventions
Cohort 1
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 100 mg orally (PO).
Intervention: Erlotinib
Cohort 1
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 100 mg orally (PO).
Intervention: Pertuzumab
Cohort 2
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 150 mg orally (PO).
Intervention: Erlotinib
Cohort 2
Participants will receive IV infusion of pertuzumab at a loading dose of 840 mg on Day 1, followed by a dose of 420 mg every 3 weeks. Erlotinib will be administered daily, at a dose level of 150 mg orally (PO).
Intervention: Pertuzumab
Outcomes
Primary Outcomes
Percentage of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: From baseline to end of the study (up to 42 weeks)
A DLT was defined as: Any non-hematological toxicity ≥ Grade 3 according to the Common Terminology Criteria for Adverse Events, version 3.0, except for fever, chills, and flu-like symptoms, which occurred despite adequate participant management. The following Grade 1-3 toxicities were exempt: Grade 1-3 skin and/or epithelial toxicities consistent with erlotinib single agent therapy, unless they did not respond to treatment or dose reduction or interruption (Grade 4 skin and/or epithelial toxicities were considered to be a DLT); Grade 4 neutropenia occurring for \> 7 days; febrile neutropenia which occurred despite adequate participant management; Grade 4 thrombocytopenia or any thrombocytopenia requiring platelet transfusion; and any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds.
Secondary Outcomes
- Percentage of Participants Classified as Responders(within 18 weeks)
- Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6(From baseline to the end of the study (up to 42 weeks))
- Peak Plasma Concentration (Cmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Time of Cmax (Tmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Area Under the Plasma Concentration Versus Time Curve (AUC) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With Non-small Cell Lung Cancer (NSCLC)(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Volume of Distribution at Steady-state (Vss) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Clearance (CL) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)
- Terminal Phase Plasma Half-life (t ½) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC(on day 1 of cycle 2, 1 hour pre-dose and 0.5, 1.5, 4, 8, 24, 168, 336 and 504 hours after the start of the infusion)