Safety and Effect of Pertuzumab in Patients With Advanced Non-Small Cell Lung Cancer, Which Has Progressed After Prior Chemotherapy

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase II, Open-label, Multicenter Study to Evaluate the Effect of Tumor-based HER2 Activation on the Efficacy of rhuMAb 2C4 (Pertuzumab) in Subjects With Recurrent Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00063154
• Other study ID #: TOC2572g
• Status: Completed
• Phase: Phase 2
• First received: June 20, 2003
• Last updated: June 8, 2015
• Start date: July 2003
• Est. completion date: April 2005

Study information

• Verified date: June 2015
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if the study drug pertuzumab is effective in treating patients with advanced lung cancer that has recurred following prior chemotherapy.

Other known NCT identifiers

• NCT00095602

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: April 2005
• Est. primary completion date: April 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed informed consent

• Tumor accessible to biopsy and willingness to undergo tumor biopsy

• Age >= 18 years

• Recurrent, histologically documented NSCLC, i.e., squamous cell, adeno-, or large cell anaplastic carcinoma. A cytologic diagnosis is acceptable (i.e. fine-needle aspiration or pleural fluid cytology).

• Measurable disease with at least one lesion that can be accurately measured in at least one dimension (bilateral dimensions should be recorded). Each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or >= 10 mm when measured by spiral CT.

• Progression of disease during, or after completion of, at least one prior chemotherapy regimen, which should have contained either a platinum, a taxane or a vinca alkaloid (e.g. vinorelbine). There is no upper limit on the number of prior chemotherapy regimens each subject may have received.

• Recovery from reversible acute effects of prior chemotherapy regimens or radiotherapy to NCI-CTC Grade <= 1 (excluding alopecia)

• ECOG performance status of 0 or 1

• Use of an effective means of contraception for men, or for women of childbearing potential

• Absolute neutrophil count >= 1500/mL, platelet count of >= 75,000/mL and hemoglobin >= 9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbepoetin [Aranesp] is permitted)

• Serum bilirubin <= 1.5 x the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <= 2.5 x ULN (ALT, AST, and alkaline phosphatase <= 5 x ULN for subjects with liver metastases)

• Serum creatinine <= 1.5 x ULN

• Internalized normalized ratio (INR) < 1.5 and activated partial thromboplastin time (aPTT) < 1.5 ULN (except for subjects receiving warfarin)

Exclusion Criteria:

• Prior treatment with any HER pathway inhibitors (e.g., Herceptin [Trastuzumab], Iressa [gefitinib], Tarceva [erlotinib hydrochloride], C225, CI1033, TAK165

• Treatment with other experimental anti-cancer agents within 4 weeks prior to Day 1

• Histologically documented bronchioalveolar carcinoma

• History or clinical or radiographic evidence of central nervous system or brain metastases

• Ejection fraction, determined by ECHO, <50%

• Uncontrolled hypercalcemia (> 11.5 mg/dL)

• Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2 mitoxantrone, or > 90 mg/m2 idarubicin

• Ongoing corticosteroid treatment, except for subjects who are on stable doses of < 20 mg of prednisone daily (or equivalent), or for subjects who are taking corticosteroids for non-malignant conditions

• History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer

• History of serious systemic disease, uncontrolled hypertension (diastolic blood pressure > 100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)

• Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

• Active infection requiring IV antibiotics

• Known human immunodeficiency virus infection

• Pregnancy or lactation

• Major surgery or significant traumatic injury within 3 weeks prior to Day 1, with the exception of tumor biopsy for the purposes of the study

• Inability to comply with study and follow-up procedures

• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Pertuzumab
Pertuzumab was supplied as a single-use liquid formulation.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cedars-Sinai Comprehensive Cancer Center	Los Angeles	California
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Memorial-Sloan Kettering Cancer Center	New York	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	Arizona Cancer Center	Scottsdale	Arizona
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)	A best overall response could occur at any time during the study and was determined by Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions (TL) or the disappearance of all non-TLs and normalization of tumor marker level. A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the treatment started for TLs and the persistence of 1 or more non-TL(s) and/or the maintenance of tumor marker level above normal limits. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.	Baseline to the end of the study (up to 1 year)	No
Secondary	Number of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) With HER2 Phosphorylation + or - Tumors	A best overall response could occur at any time during the study and was determined by Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions (TL) or the disappearance of all non-TLs and normalization of tumor marker level. A PR was defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the treatment started for TLs and the persistence of 1 or more non-TL(s) and/or the maintenance of tumor marker level above normal limits. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started or the appearance of one or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.	Baseline to the end of the study (up to 1 year)	No
Secondary	Progression-free Survival	Progression-free survival was defined as the time from the first day of pertuzumab treatment (Cycle 1, Day 1) to the time of documented disease progression (per RECIST) or death, whichever occurred first.	Baseline to the end of the study (up to 1 year)	No
Secondary	Number of Participants Free From Disease Progression at 3, 6, and 12 Months	Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.	Baseline to the end of the study (up to 1 year)	No