Non-small Cell Lung Cancer
Conditions
Keywords
Lung cancer
Brief 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.
Interventions
DRUGPertuzumab
Pertuzumab was supplied as a single-use liquid formulation.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) | Baseline to the end of the study (up to 1 year) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline to the end of the study (up to 1 year) | 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. |
| Progression-free Survival | Baseline to the end of the study (up to 1 year) | 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. |
| Number of Participants Free From Disease Progression at 3, 6, and 12 Months | Baseline to the end of the study (up to 1 year) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pertuzumab Participants received pertuzumab intravenously on Day 1 of every 3 week cycle for up to 1 year (up to 17 treatment cycles). Subjects received pertuzumab at a loading dose of 840 mg in Cycle 1 followed by a dose of 420 mg in Cycles 2 and beyond. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 3 |
| Overall Study | Did not receive treatment | 8 |
| Overall Study | Disease progression | 27 |
| Overall Study | Physician Decision | 10 |
| Overall Study | Reason unspecified | 1 |
Baseline characteristics
| Characteristic | Pertuzumab |
|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 42 / 43 |
| serious Total, serious adverse events | 15 / 43 |
Outcome results
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.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: Participants who received at least 2 doses of pertuzumab and either underwent at least 1 post-baseline assessment of response or died as a result of disease progression before any evaluation of response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pertuzumab | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) | Complete response | 0.0 percentage of participants |
| Pertuzumab | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) | Partial response | 0.0 percentage of participants |
| Pertuzumab | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) | Stable disease | 51.4 percentage of participants |
| Pertuzumab | Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) | Progressive disease | 48.6 percentage of participants |
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.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: Participants who received at least 2 doses of pertuzumab and either underwent at least 1 post-baseline assessment of response or died as a result of disease progression before any evaluation of response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pertuzumab | Number of Participants Free From Disease Progression at 3, 6, and 12 Months | 3 months | 8 participants |
| Pertuzumab | Number of Participants Free From Disease Progression at 3, 6, and 12 Months | 6 months | 1 participants |
| Pertuzumab | Number of Participants Free From Disease Progression at 3, 6, and 12 Months | 9 months | 0 participants |
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.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: Participants who received at least 2 doses of pertuzumab and either underwent at least 1 post-baseline assessment of response or died as a result of disease progression before any evaluation of response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pertuzumab | 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 | Partial response pHER2- (n=34) | 0 participants |
| Pertuzumab | 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 | Progressive disease pHER2- (n=34) | 13 participants |
| Pertuzumab | 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 | Complete response pHER2+ (n=4) | 0 participants |
| Pertuzumab | 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 | Partial response pHER2+ (n=4) | 0 participants |
| Pertuzumab | 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 | Stable disease pHER2+ (n=4) | 2 participants |
| Pertuzumab | 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 | Progressive disease pHER2+ (n=4) | 1 participants |
| Pertuzumab | 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 | No tumor assessment pHER2+ (n=4) | 1 participants |
| Pertuzumab | 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 | Unable to evaluate response pHER2+ (n=4) | 0 participants |
| Pertuzumab | 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 | Complete response pHER2- (n=34) | 0 participants |
| Pertuzumab | 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 | Stable disease pHER2- (n=34) | 15 participants |
| Pertuzumab | 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 | No tumor assessment pHER2- (n=34) | 5 participants |
| Pertuzumab | 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 | Unable to evaluate response pHER2- (n=34) | 1 participants |
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.
Time frame: Baseline to the end of the study (up to 1 year)
Population: Efficacy-evaluable population: Participants who received at least 2 doses of pertuzumab and either underwent at least 1 post-baseline assessment of response or died as a result of disease progression before any evaluation of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pertuzumab | Progression-free Survival | 6.6 weeks |