Back to resultsA Study of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer (PENGUIN)
Primary Purpose
Non-Small Cell Lung Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pertuzumab
Erlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Tarceva, NSCLC
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed non-small cell lung cancer (NSCLC).
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
- Recurrent or progressive disease after receiving at least 1, but no more than two, chemotherapy regimens for advanced or metastatic NSCLC.
- Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 (excluding alopecia).
- Ability to comply with the study and follow-up procedures, including all specified imaging studies.
- Ability to take oral medication.
- Life expectancy ≥ 3 months.
- Measurable disease on computed tomography (CT).
- At least 1 extracerebral lesion on 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) scan that is suitable for response assessment, that is measurable, and ≥ 15 mm on CT.
- Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by echocardiogram or MUltiple Gated Acquisition (MUGA) scan.
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner.
- Availability and willingness to provide sufficient tumor tissue for testing for epidermal growth factor receptor (EGFR) mutations, and other human epidermal growth factor receptor (HER) pathway and NSCLC-related biomarkers.
Exclusion Criteria:
- Prior treatment with an investigational or marketed agent for the purpose of inhibiting HER family members (including HER1, HER2, HER3, and HER4). This includes, but is not limited to erlotinib, gefitinib, pertuzumab, cetuximab, and panitumumab.
- Chemotherapy, radiotherapy, or investigational treatment within 28 days of start of study (ie, prior to Day 0) or from which patients have not yet recovered.
- Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption.
- Uncontrolled diabetes.
- Clinical or radiographic evidence of new or progression of pre-existing central nervous system (CNS) metastases.
- Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers; or bone fractures).
- Current uncontrolled hypertension or unstable angina.
- History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia).
- History of myocardial infarction within 6 months of enrollment or history of unstable angina.
- Any evidence of an unstable infection as suggested by an infectious process, coupled with hypotension and/or tachycardia and/or fever and/or positive blood culture.
- Known human immunodeficiency virus (HIV) infection.
- Uncontrolled hypercalcemia.
- Pregnancy or lactation.
- History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90%.
- Claustrophobia.
- Any other disease, condition, physical examination finding, or clinical laboratory finding that, in the opinion of the investigator, makes the patient inappropriate for the study.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pertuzumab + erlotinib
Arm Description
Patients received pertuzumab 840 mg intravenously (IV) 1 time (loading dose) followed by 420 mg IV (maintenance dose) every 3 weeks (q3w) plus erlotinib 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
Outcomes
Primary Outcome Measures
Percentage of Patients With a 2-deoxy-2-[18F]Fluoro-D-glucose-positron Emission Tomography (FDG-PET) Response at Day 56 in All Patients and in Epidermal Growth Factor Receptor (EGFR) Mutant and Wild-type Subgroups
The assessment of FDG-PET response was performed by a central reading site. PET response was based on the maximum standard uptake value (SUVmax) of up to 5 regions of interest (ROI). The tumor ROIs were identified for each patient on pretreatment FDG-PET scans and corresponded to a subset of the target lesions identified for Response Evaluation Criteria for Solid Tumors (RECIST) analysis. Specifically, the SUVmax of each ROI on the on-treatment scans was compared with the SUVmax on the corresponding pretreatment scan and the percent change was calculated. When there was more than 1 ROI, the overall percent change in SUVmax was the arithmetic mean of the percent changes in SUVmax for each of the ROIs (mSUVmax). An PET response is defined as a decrease of ≥ 20% in mSUVmax. EGFR mutation status was assessed in tumor tissue samples taken from each patient.
Secondary Outcome Measures
Progression-free Survival (PFS)
PFS was defined as the time from the first dosing with pertuzumab and erlotinib to the first occurrence of disease progression (PD), as determined by the investigator and based on computed tomography using Response Evaluation Criteria in Solid Tumors (RECIST), or death from any cause, whichever comes first. PD was defined as ≥ 20% increase in the sum of the longest diameter of target lesions (TL), taking as reference the smallest sum longest diameter recorded since treatment started, the unequivocal progression of existing non-target lesions (non-TL), or the appearance of 1 or more new lesions. TLs were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as TLs. All other lesions (or sites of disease) were identified as non-TLs.
Overall Survival (OS)
Overall survival was defined as the time from the date of first dosing with pertuzumab and erlotinib until the date of patient death from any cause.
Percentage of Patients With an Objective Response (OR)
OR was defined as a complete response (CR) or a partial response (PR) as determined by the investigator and based on computed tomography (CT) using Response Evaluation Criteria in Solid Tumors (RECIST) on 2 consecutive occasions at least 4 weeks apart. A complete response was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. A partial response was defined as ≥ 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or the persistence of 1 or more non-target lesions and/or the maintenance of a tumor marker level above the normal limits.
Percentage of Patients With Disease Control (DC) at Day 56
DC was defined as a CR, a PR, or stable disease (SD) as determined by the investigator and based on CT using RECIST. A CR was defined as the disappearance of all target (TL) and non-target lesions (nTL). A PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline sum longest diameter, or the persistence of 1 or more nTLs and/or maintenance of a tumor marker level (TML) above normal limits. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (SSLD) since treatment started. For nTLs, SD was defined as the persistence of 1 or more lesions and/or maintenance of a TML above normal limits. PD was defined as ≥ 20% increase in the SLD of TLs, taking as reference the SSLD recorded since treatment started, the appearance of 1 or more new lesions, or the unequivocal progression of existing nTLs.
Full Information
NCT ID
NCT00855894
First Posted
March 4, 2009
Last Updated
May 14, 2013
Sponsor
Genentech, Inc.
Collaborators
Roche Pharma AG
1. Study Identification
Unique Protocol Identification Number
NCT00855894
Brief Title
A Study of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
Acronym
PENGUIN
Official Title
An Open-label Phase II Multicenter Study of the Safety and Activity (as Measured by FDG-PET Imaging Changes) of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
Collaborators
Roche Pharma AG
4. Oversight
5. Study Description
Brief Summary
This was a Phase II, open-label, single-arm, single-stage, multicenter trial in patients with relapsed non-small cell lung cancer (NSCLC), with the objective of assessing the activity of the combination of erlotinib and pertuzumab on the basis of the endpoint of FDG-PET response rate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
Keywords
Tarceva, NSCLC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pertuzumab + erlotinib
Arm Type
Experimental
Arm Description
Patients received pertuzumab 840 mg intravenously (IV) 1 time (loading dose) followed by 420 mg IV (maintenance dose) every 3 weeks (q3w) plus erlotinib 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
Intervention Type
Drug
Intervention Name(s)
Pertuzumab
Other Intervention Name(s)
Perjeta
Intervention Description
After a single administration of a loading dose of 840 mg IV, patients received a maintenance dose of 420 mg IV every 3 weeks (q3w).
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
Patients received 150 mg orally once a day which was reduced to 100 mg orally once a day in a protocol amendment dated 19 May 2010.
Primary Outcome Measure Information:
Title
Percentage of Patients With a 2-deoxy-2-[18F]Fluoro-D-glucose-positron Emission Tomography (FDG-PET) Response at Day 56 in All Patients and in Epidermal Growth Factor Receptor (EGFR) Mutant and Wild-type Subgroups
Description
The assessment of FDG-PET response was performed by a central reading site. PET response was based on the maximum standard uptake value (SUVmax) of up to 5 regions of interest (ROI). The tumor ROIs were identified for each patient on pretreatment FDG-PET scans and corresponded to a subset of the target lesions identified for Response Evaluation Criteria for Solid Tumors (RECIST) analysis. Specifically, the SUVmax of each ROI on the on-treatment scans was compared with the SUVmax on the corresponding pretreatment scan and the percent change was calculated. When there was more than 1 ROI, the overall percent change in SUVmax was the arithmetic mean of the percent changes in SUVmax for each of the ROIs (mSUVmax). An PET response is defined as a decrease of ≥ 20% in mSUVmax. EGFR mutation status was assessed in tumor tissue samples taken from each patient.
Time Frame
Baseline to Day 56
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS was defined as the time from the first dosing with pertuzumab and erlotinib to the first occurrence of disease progression (PD), as determined by the investigator and based on computed tomography using Response Evaluation Criteria in Solid Tumors (RECIST), or death from any cause, whichever comes first. PD was defined as ≥ 20% increase in the sum of the longest diameter of target lesions (TL), taking as reference the smallest sum longest diameter recorded since treatment started, the unequivocal progression of existing non-target lesions (non-TL), or the appearance of 1 or more new lesions. TLs were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as TLs. All other lesions (or sites of disease) were identified as non-TLs.
Time Frame
Baseline to the end of the study (up to 3 years)
Title
Overall Survival (OS)
Description
Overall survival was defined as the time from the date of first dosing with pertuzumab and erlotinib until the date of patient death from any cause.
Time Frame
Baseline to the end of the study (up to 3 years)
Title
Percentage of Patients With an Objective Response (OR)
Description
OR was defined as a complete response (CR) or a partial response (PR) as determined by the investigator and based on computed tomography (CT) using Response Evaluation Criteria in Solid Tumors (RECIST) on 2 consecutive occasions at least 4 weeks apart. A complete response was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. A partial response was defined as ≥ 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or the persistence of 1 or more non-target lesions and/or the maintenance of a tumor marker level above the normal limits.
Time Frame
Baseline to the end of the study (up to 3 years)
Title
Percentage of Patients With Disease Control (DC) at Day 56
Description
DC was defined as a CR, a PR, or stable disease (SD) as determined by the investigator and based on CT using RECIST. A CR was defined as the disappearance of all target (TL) and non-target lesions (nTL). A PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline sum longest diameter, or the persistence of 1 or more nTLs and/or maintenance of a tumor marker level (TML) above normal limits. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (SSLD) since treatment started. For nTLs, SD was defined as the persistence of 1 or more lesions and/or maintenance of a TML above normal limits. PD was defined as ≥ 20% increase in the SLD of TLs, taking as reference the SSLD recorded since treatment started, the appearance of 1 or more new lesions, or the unequivocal progression of existing nTLs.
Time Frame
Baseline to Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed non-small cell lung cancer (NSCLC).
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
Recurrent or progressive disease after receiving at least 1, but no more than two, chemotherapy regimens for advanced or metastatic NSCLC.
Recovery from reversible acute effects of prior anti-cancer therapy (chemotherapy, radiotherapy, or investigational treatment) to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≤ 1 (excluding alopecia).
Ability to comply with the study and follow-up procedures, including all specified imaging studies.
Ability to take oral medication.
Life expectancy ≥ 3 months.
Measurable disease on computed tomography (CT).
At least 1 extracerebral lesion on 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography (FDG-PET) scan that is suitable for response assessment, that is measurable, and ≥ 15 mm on CT.
Left ventricular ejection fraction (LVEF) ≥ 50%, as determined by echocardiogram or MUltiple Gated Acquisition (MUGA) scan.
For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner.
Availability and willingness to provide sufficient tumor tissue for testing for epidermal growth factor receptor (EGFR) mutations, and other human epidermal growth factor receptor (HER) pathway and NSCLC-related biomarkers.
Exclusion Criteria:
Prior treatment with an investigational or marketed agent for the purpose of inhibiting HER family members (including HER1, HER2, HER3, and HER4). This includes, but is not limited to erlotinib, gefitinib, pertuzumab, cetuximab, and panitumumab.
Chemotherapy, radiotherapy, or investigational treatment within 28 days of start of study (ie, prior to Day 0) or from which patients have not yet recovered.
Inability to take oral medications, disease affecting gastrointestinal absorption, or prior surgical procedure affecting gastrointestinal absorption.
Uncontrolled diabetes.
Clinical or radiographic evidence of new or progression of pre-existing central nervous system (CNS) metastases.
Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers; or bone fractures).
Current uncontrolled hypertension or unstable angina.
History of congestive heart failure (CHF) of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia).
History of myocardial infarction within 6 months of enrollment or history of unstable angina.
Any evidence of an unstable infection as suggested by an infectious process, coupled with hypotension and/or tachycardia and/or fever and/or positive blood culture.
Known human immunodeficiency virus (HIV) infection.
Uncontrolled hypercalcemia.
Pregnancy or lactation.
History of another malignancy in the past 2 years, unless the malignancy has been adequately treated, is currently not detectable, and is associated with a 5-year survival > 90%.
Claustrophobia.
Any other disease, condition, physical examination finding, or clinical laboratory finding that, in the opinion of the investigator, makes the patient inappropriate for the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Pirzkall, M.D.
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Adelaide
ZIP/Postal Code
5000
Country
Australia
City
Chermside
ZIP/Postal Code
4032
Country
Australia
City
East Melbourne
ZIP/Postal Code
3002
Country
Australia
City
Heidelberg
ZIP/Postal Code
3084
Country
Australia
City
Herston
ZIP/Postal Code
4029
Country
Australia
City
Sydney
ZIP/Postal Code
2065
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
24457379
Citation
Hughes B, Mileshkin L, Townley P, Gitlitz B, Eaton K, Mitchell P, Hicks R, Wood K, Amler L, Fine BM, Loecke D, Pirzkall A. Pertuzumab and erlotinib in patients with relapsed non-small cell lung cancer: a phase II study using 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Oncologist. 2014 Feb;19(2):175-6. doi: 10.1634/theoncologist.2013-0026. Epub 2014 Jan 23.
Results Reference
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A Study of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
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