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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00855894




Registration number
NCT00855894
Ethics application status
Date submitted
4/03/2009
Date registered
4/03/2009
Date last updated
14/05/2013

Titles & IDs
Public title
A Study of the Combination of Erlotinib and Pertuzumab in Patients With Relapsed Non-small Cell Lung Cancer
Scientific 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
Secondary ID [1] 0 0
GO01357
Secondary ID [2] 0 0
TOC4603g
Universal Trial Number (UTN)
Trial acronym
PENGUIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Erlotinib

Experimental: Pertuzumab + erlotinib - 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.


Treatment: Drugs: Pertuzumab
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).

Treatment: Drugs: Erlotinib
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to Day 56
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to the end of the study (up to 3 years)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline to the end of the study (up to 3 years)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline to the end of the study (up to 3 years)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline to Day 56

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Chermside
Recruitment hospital [3] 0 0
- East Melbourne
Recruitment hospital [4] 0 0
- Heidelberg
Recruitment hospital [5] 0 0
- Herston
Recruitment hospital [6] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
2065 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Nebraska
Country [3] 0 0
United States of America
State/province [3] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Roche Pharma AG
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00855894
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andrea Pirzkall, M.D.
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications