Pancreatic Cancer
Conditions
Brief summary
This study is designed to identify biomarkers which may predict improvement in progression free survival from treatment with Tarceva, in patients with advanced pancreatic cancer who failed one prior regimen of standard chemotherapy or who are deemed unsuitable for chemotherapy. It will also assess the efficacy and safety of Tarceva in this patient population. Patients will be randomized to receive either Tarceva 150mg/day po, or placebo po daily. Tumor tissue will be used for biomarker analysis. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGErlotinib
Participants received erlotinib 150 mg tablet orally once daily.
DRUGPlacebo
Participants received placebo matching to erlotinib 150 mg tablet orally once daily.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * histologically or cytologically documented locally advanced-unresectable or metastatic pancreatic cancer; * measurable disease according to RECIST; * failure of at least one prior chemotherapy regimen, or who are deemed unsuitable for chemotherapy; * ECOG performance status of 0-2.
Exclusion criteria
* local or locally advanced-resectable pancreatic cancer; * any other malignancies within last 5 years, except for adequately treated cancer in situ of the cervix, or basal or squamous cell skin cancer; * major surgery within 2 weeks prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From the time of randomization until progression of disease or death (up to 30 months) | Progression-free survival (PFS) was defined as the time from the date of randomization to the date of the first occurrence of PD or death whichever occurred first. Participants without event were censored at the date of last tumor assessment where non-progression was documented. Analysis was performed using Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From the time of randomization until or death (up to 30 months) | Overall survival was defined as the time from the date of randomization to the date of death, regardless of the cause of death. |
| Percentage of Participants With Best Overall Response Rate | From the time of randomization until progression of disease or death (up to 30 months) | Response rate was defined as Complete Response (CR) or Partial Response (PR), according to response evaluation criteria in solid tumors (RECIST) Version 1.0 criteria, for at least 4 weeks at any time during randomized treatment (confirmed response). CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions. |
| Percentage of Participants With Disease Control Rate (DCR) | Randomization to Clinical Cutoff: 20 December 2010 (up to 30 months) | Disease control rates (DCR) were measured according to RECIST Version 1.0 criteria. Disease control was defined as being a responder or as having stable disease for at least 6 weeks post-randomization. Stable disease was defined as having neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. |
| Number of Participants With Adverse Events (AEs) | Up to 28 days after discontinuation of study drug (up to 30 months) | An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment, regardless of whether or not the event had a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. |
Countries
Australia, Brazil, Bulgaria, Croatia, Germany, Hong Kong, India, Italy, Latvia, Lithuania, Malaysia, Mexico, Peru, Romania, Russia, Singapore, Slovenia, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with advanced pancreatic carcinoma with Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2, who had failed 1 prior regimen of chemotherapy or who were considered unsuitable for chemotherapy, received placebo matching to erlotinib 150 mg tablet orally once daily until disease progression (PD), unacceptable toxicity, withdrawal, or death. | 103 |
| Erlotinib Participants with advanced pancreatic carcinoma with ECOG PS score of 0 to 2, who had failed 1 prior regimen of chemotherapy or who were considered unsuitable for chemotherapy, received erlotinib 150 mg orally once daily until PD, unacceptable toxicity, withdrawal, or death. | 104 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 9 |
| Overall Study | Death | 19 | 15 |
| Overall Study | Failure to Return | 1 | 0 |
| Overall Study | Insufficient Therapeutic Response | 77 | 72 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Refused Treatment | 1 | 5 |
Baseline characteristics
| Characteristic | Placebo | Erlotinib | Total |
|---|---|---|---|
| Age, Customized Greater than (>) 65 years | 31 participants | 42 participants | 73 participants |
| Age, Customized Less than (<) 65 years | 72 participants | 62 participants | 134 participants |
| Sex: Female, Male Female | 44 Participants | 45 Participants | 89 Participants |
| Sex: Female, Male Male | 59 Participants | 59 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 103 | 81 / 104 |
| serious Total, serious adverse events | 11 / 103 | 21 / 104 |
Outcome results
Primary
Progression-Free Survival
Progression-free survival (PFS) was defined as the time from the date of randomization to the date of the first occurrence of PD or death whichever occurred first. Participants without event were censored at the date of last tumor assessment where non-progression was documented. Analysis was performed using Kaplan-Meier method.
Time frame: From the time of randomization until progression of disease or death (up to 30 months)
Population: The Full-Analysis Set (FAS) was defined as all randomized patients. Participants were presented according to the therapy that they were randomized to receive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Progression-Free Survival | 5.9 weeks |
| Erlotinib | Progression-Free Survival | 6.1 weeks |
Comparison: Cox proportional hazards model was used to estimate the Hazard Ratio (erlotinib compared with placebo), including 95 percent (%) confidence intervals (CIs).p-value: 0.190995% CI: [0.63, 1.1]Log Rank
Secondary
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment, regardless of whether or not the event had a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment.
Time frame: Up to 28 days after discontinuation of study drug (up to 30 months)
Population: Safety population included all participants who received at least 1 dose of study medication and had a safety follow-up, whether withdrawn prematurely or not, were included in the safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) | 71 participants |
| Erlotinib | Number of Participants With Adverse Events (AEs) | 90 participants |
Secondary
Overall Survival
Overall survival was defined as the time from the date of randomization to the date of death, regardless of the cause of death.
Time frame: From the time of randomization until or death (up to 30 months)
Population: The FAS was defined as all randomized patients. Participants were presented according to the therapy that they were randomized to receive.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Overall Survival | 3.1 months |
| Erlotinib | Overall Survival | 4.0 months |
Secondary
Percentage of Participants With Best Overall Response Rate
Response rate was defined as Complete Response (CR) or Partial Response (PR), according to response evaluation criteria in solid tumors (RECIST) Version 1.0 criteria, for at least 4 weeks at any time during randomized treatment (confirmed response). CR was defined as the disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions.
Time frame: From the time of randomization until progression of disease or death (up to 30 months)
Population: The FAS was defined as all randomized patients. Participants were presented according to the therapy that they were randomized to receive.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Best Overall Response Rate | CR | 0 percentage of participants |
| Placebo | Percentage of Participants With Best Overall Response Rate | PR | 4 percentage of participants |
| Erlotinib | Percentage of Participants With Best Overall Response Rate | CR | 0 percentage of participants |
| Erlotinib | Percentage of Participants With Best Overall Response Rate | PR | 1 percentage of participants |
Secondary
Percentage of Participants With Disease Control Rate (DCR)
Disease control rates (DCR) were measured according to RECIST Version 1.0 criteria. Disease control was defined as being a responder or as having stable disease for at least 6 weeks post-randomization. Stable disease was defined as having neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time frame: Randomization to Clinical Cutoff: 20 December 2010 (up to 30 months)
Population: The FAS was defined as all randomized patients. Participants were presented according to the therapy that they were randomized to receive.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Disease Control Rate (DCR) | 19 percentage of participants |
| Erlotinib | Percentage of Participants With Disease Control Rate (DCR) | 29 percentage of participants |