A Study of Pertuzumab With Erlotinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

NCT02507375 | Completed Phase 1 Results

• 1 other identifier: WO20024
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 3

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Squamous

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  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.

  From baseline to end of the study (up to 42 weeks)

Secondary Outcomes (8)

• 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

• 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

Study Arms (2)

Cohort 1

EXPERIMENTAL

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).

Drug: Erlotinib; Drug: Pertuzumab

Cohort 2

EXPERIMENTAL

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).

Drug: Erlotinib; Drug: Pertuzumab

Interventions

Erlotinib DRUG

Erlotinib will be administered as oral tablets.

Also known as: Tarceva

Cohort 1; Cohort 2

Pertuzumab DRUG

Pertuzumab will be administered as intravenous (IV) infusion.

Also known as: Perjeta

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Unknown Facility

Antwerp, 2020, Belgium

Location

Unknown Facility

Barcelona, 08035, Spain

Location

Unknown Facility

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; pertuzumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Per Version A the protocol was halted for 2 DLTs (grade 3 manageable rash common for erlotinib) in the first 6 patients. Ethics committee approved redefining DLT and starting anew with Version B. No further DLTs were observed throughout the study.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 23, 2015
• Study Start: September 1, 2006
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 16, 2015
• Results First Posted: October 16, 2015

Record last verified: 2015-09

Locations

GB (1); ES (1); BE (1)