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

• ClinicalTrials.gov Identifier: NCT02507375
• Recruitment Status: Completed
• First Posted: July 23, 2015
• Results First Posted: October 16, 2015
• Last Update Posted: October 16, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: July 14, 2015
• First Posted Date: July 23, 2015
• Results First Submitted Date: July 31, 2015
• Results First Posted Date: October 16, 2015
• Last Update Posted Date: October 16, 2015
• Study Start Date: September 2006
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2015)

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.

Original Primary Outcome Measures (submitted: July 22, 2015)

• Percentage of participants With Maximum Tolerated Dose (MTD) [ Time Frame: From Day -8 of cycle 1 until end of cycle 6, up to 18 weeks, or earlier in case of treatment discontinuation because of disease progression or unacceptable toxicity ]
• Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: From Day -8 of cycle 1 until end of cycle 6, up to 18 weeks, or earlier in case of treatment discontinuation because of disease progression or unacceptable toxicity ]

Current Secondary Outcome Measures (submitted: September 18, 2015)

• Percentage of Participants Classified as Responders [ Time Frame: within 18 weeks ]
  Responders are participants who achieved either a complete response or a partial response according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
• Percentage of Participants With a Complete Response or Partial Response at the End of Cycles 1, 2, 3, 4, and 6 [ Time Frame: From baseline to the end of the study (up to 42 weeks) ]
  Complete and partial responses were determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A complete response was defined as the disappearance of all target and non-target lesions. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter.
• Peak Plasma Concentration (Cmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC [ Time Frame: 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 ]
  Maximum Observed Plasma Concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, typically measured in nanograms/milliliter (ng/mL), reported as mg/L.
• Time of Cmax (Tmax) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC [ Time Frame: 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 ]
  The time at which maximum concentration (Cmax), which is the maximum (peak) concentration (amount of drug) measurable in blood plasma after a dose is administered, is reached (Tmax).
• Terminal Phase Plasma Half-life (t ½) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC [ Time Frame: 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) is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, rather than the time required to eliminate half the administered dose.
• 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) [ Time Frame: 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 ]
  Bioavailability [AUC(0-t)] is a measure of how much of the drug reaches the person's bloodstream from time 0 (pre-dose) to a given time point (t) for the body to use. The extent of product bioavailability is estimated by the area under the blood concentration vs time curve. The Area Under the Curve (AUC) is calculated by plotting the drug's blood levels on a graph at different times during the set period. The area under this curve reflects the amount of drug exposure in the set time period, calculated as hour * nanograms (ng) per milliliter (mL), which equates to mg.day/L. Bioavailability Extrapolated to Infinity [AUC (0-inf)] is a calculated measure of how much of the drug will ever reach the person's bloodstream for the body to use. AUC (0-inf) stands for the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (forever). It is obtained from calculating AUC (0-t) plus AUC (t-inf).
• Clearance (CL) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC [ Time Frame: 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 ]
  A fundamental concept in pharmacokinetics is drug clearance (CL), that is, elimination of drugs from the body. The clearance is simply the ratio of the dose to the area under the curve (AUC), so that the higher the AUC for a given dose, the lower the clearance. If a drug is administered by continuous infusion and a steady state is achieved, the clearance can be estimated from a single measurement of the plasma drug concentration.
• Volume of Distribution at Steady-state (Vss) for Pertuzumab (Cycle 2) in the Presence of Erlotinib (at Steady-state) in Patients With NSCLC [ Time Frame: 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 ]
  Steady-state volume of distribution of a drug is an estimate of drug distribution independent of elimination processes. It is most useful for predicting the plasma concentrations following multiple dosing to a steady-state or pseudo-equilibrium. Vss is proportional to the amount of drug in the body versus the plasma concentration of the drug at steady state (pseudo-equilibrium). It is a calculated measure.

Original Secondary Outcome Measures (submitted: July 22, 2015)

• Percenatge of participants with complete response [ Time Frame: From Day -8 of cycle 1 until end of cycle 6, up to 18 weeks, or earlier in case of treatment discontinuation because of disease progression or unacceptable toxicity ]
• Area under the plasma concentration versus time curve (AUC) [ Time Frame: From Day -1 until Day 22 ]
• Clearance (CL): pertuzumab\nClearance at steady-state (CLss): erlotinib [ Time Frame: From Day -1 until Day 22 ]
• Volume of distribution at steady-state (Vss) [ Time Frame: From Day -1 until Day 22 ]
• Percenatge of participants with partial response [ Time Frame: From Day -8 of cycle 1 until end of cycle 6, up to 18 weeks, or earlier in case of treatment discontinuation because of disease progression or unacceptable toxicity ]
• Peak Plasma Concentration (Cmax) [ Time Frame: From Day -1 until Day 22 ]
• Time of Cmax (Tmax) [ Time Frame: From Day -1 until Day 22 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pertuzumab With Erlotinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
• Official Title: 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.
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

• Drug: Erlotinib
  Erlotinib will be administered as oral tablets.
  Other Name: Tarceva
• Drug: Pertuzumab
  Pertuzumab will be administered as intravenous (IV) infusion.
  Other Name: Perjeta

Study Arms

• Experimental: 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).
  Interventions:

  • Drug: Erlotinib
  • Drug: Pertuzumab
• Experimental: 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).
  Interventions:

  • Drug: Erlotinib
  • Drug: Pertuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 22, 2015): 17
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2008
• Actual Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Spain, United Kingdom

Administrative Information

• NCT Number: NCT02507375
• Other Study ID Numbers: WO20024
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: September 2015