Pancreatic Cancer
Conditions
Brief summary
This single arm study will evaluate the relationship between the skin toxicity of Tarceva in combination with gemcitabine, and survival, in patients with advanced and/or metastatic pancreatic cancer. All patients will receive gemcitabine 100mg/m2 i.v. weekly; Tarceva will be administered 100mg po per day. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGErlotinib
100 mg, PO, once per day
DRUGGemcitabine
1000 mg/m2, IV, on Days 1, 8 and 15 in 4-week cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * locally advanced and/or metastatic pancreatic cancer (stage III or IV); * Karnofsky performance Status of \>=60%.
Exclusion criteria
* local(stage IA to IIB) pancreatic cancer; * \<=6 months since last adjuvant chemotherapy; * previous systemic therapy for metastatic pancreatic cancer; * other primary tumor within last 5 years (except for adequately treated cancer in situ of cervix, or basal cell skin cancer); * clinically significant cardiovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died During the Study | Enrollment through Cycle 24 (4-week cycles), up to 24 months. | — |
| Overall Survival (OS) During the Study | Enrollment through Cycle 24 (4-week cycles), up to 24 months. | OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died During the Study By Rash Grade | Enrollment through Cycle 24 (4-week cycles), up to 24 months. | — |
| OS By Rash Grade | Enrollment through Cycle 24 (4-week cycles), up to 24 months. | OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology. |
| Number of Participants With Disease Progression or Death | Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months. | Progression-free survival (PFS) was defined as the time from the date of enrollment to the date of document disease progression or death due to any cause. As per Response Evaluation Criteria in Solid Tumors (RECIST) V 1.0, progressive disease (PD) was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants whose last recorded status was not PD or death were censored. |
| Number of Participants Who Died at 6 Months | Enrollment through Cycle 6 (4-week cycles), up to 6 months. | — |
| Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST | Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months. | As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR. |
| Percentage of Participants With Disease Control According to RECIST | Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months. | Disease control was defined as BOR of CR, PR, or stable disease (SD). As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR. |
| PFS | Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months | The time, in months, from enrollment to PFS event. Participants whose last recorded status was not progression or death were censored. PFS was estimated using Kaplan-Meier methodology. |
| OS At 6 Months | Enrollment through Cycle 6 (4-week cycles), up to 6 months. | OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 Participants with a rash Grade \< 2 according to the National NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. | 115 |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 Participants with a rash Grade ≥ 2 according to the NCI-CTC V 3.0 received erlotinib, 100 mg, PO, once per day of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. Participants also received gemcitabine, 1000 mg/m\^2, IV, over 30 minutes on Days 1, 8 and 15 of Cycles 1 up through a maximum of Cycle 24 (4-week cycles) until disease progression, unacceptable toxicity, or treatment refusal by participant. | 38 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 7 |
| Overall Study | Death | 8 | 1 |
| Overall Study | Lack of Efficacy | 68 | 20 |
| Overall Study | Other | 4 | 4 |
| Overall Study | Physician Decision | 10 | 4 |
| Overall Study | Withdrawal by Subject | 8 | 2 |
Baseline characteristics
| Characteristic | Erlotinib, Gemcitabine: Rash Grade < 2 | Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.9 | 62.0 years STANDARD_DEVIATION 10.6 | 63.2 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 61 Participants | 10 Participants | 71 Participants |
| Sex: Female, Male Male | 54 Participants | 28 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 115 | 38 / 38 |
| serious Total, serious adverse events | 58 / 115 | 14 / 38 |
Outcome results
Primary
Number of Participants Who Died During the Study
Time frame: Enrollment through Cycle 24 (4-week cycles), up to 24 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Number of Participants Who Died During the Study | 102 participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Number of Participants Who Died During the Study | 27 participants |
Primary
Overall Survival (OS) During the Study
OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.
Time frame: Enrollment through Cycle 24 (4-week cycles), up to 24 months.
Population: ITT population; only participants who died were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Overall Survival (OS) During the Study | 4.468 months |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Overall Survival (OS) During the Study | 10.546 months |
Secondary
Number of Participants Who Died at 6 Months
Time frame: Enrollment through Cycle 6 (4-week cycles), up to 6 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Number of Participants Who Died at 6 Months | 69 participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Number of Participants Who Died at 6 Months | 8 participants |
Secondary
Number of Participants Who Died During the Study By Rash Grade
Time frame: Enrollment through Cycle 24 (4-week cycles), up to 24 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Number of Participants Who Died During the Study By Rash Grade | 65 participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Number of Participants Who Died During the Study By Rash Grade | 37 participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Number of Participants Who Died During the Study By Rash Grade | 27 participants |
Secondary
Number of Participants With Disease Progression or Death
Progression-free survival (PFS) was defined as the time from the date of enrollment to the date of document disease progression or death due to any cause. As per Response Evaluation Criteria in Solid Tumors (RECIST) V 1.0, progressive disease (PD) was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants whose last recorded status was not PD or death were censored.
Time frame: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Number of Participants With Disease Progression or Death | 110 participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Number of Participants With Disease Progression or Death | 33 participants |
Secondary
OS At 6 Months
OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.
Time frame: Enrollment through Cycle 6 (4-week cycles), up to 6 months.
Population: ITT population; only participants who died were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | OS At 6 Months | 4.468 months |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | OS At 6 Months | NA months |
Secondary
OS By Rash Grade
OS was defined as the time, in months, from the date of enrollment to the date of death due to any cause. Participants whose last recorded status was not death were censored. OS was estimated using Kaplan-Meier methodology.
Time frame: Enrollment through Cycle 24 (4-week cycles), up to 24 months.
Population: ITT population; only participants who died were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | OS By Rash Grade | 3.318 months |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | OS By Rash Grade | 6.571 months |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | OS By Rash Grade | 10.546 months |
Secondary
Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST
As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR.
Time frame: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST | 7.0 percentage of participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to RECIST | 21.1 percentage of participants |
p-value: <0.05Chi-squared
Secondary
Percentage of Participants With Disease Control According to RECIST
Disease control was defined as BOR of CR, PR, or stable disease (SD). As per RECIST V 1.0: for TLs, a CR was defined as the disappearance of all TLs; and a PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD; SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. For NTLs, a CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. Participants for whom no assessment of response was available and who had finalized the study due to disease progression or tumor-related death, disease progression was considered the BOR.
Time frame: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months.
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | Percentage of Participants With Disease Control According to RECIST | 42.6 percentage of participants |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | Percentage of Participants With Disease Control According to RECIST | 84.2 percentage of participants |
p-value: <0.05Chi-squared
Secondary
PFS
The time, in months, from enrollment to PFS event. Participants whose last recorded status was not progression or death were censored. PFS was estimated using Kaplan-Meier methodology.
Time frame: Enrollment, every 2 treatment cycles (4-week cycles) until disease progression, death, or end of study, for up to 24 months
Population: ITT population; only participants with an event (death or disease progression) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib, Gemcitabine: Rash Grade < 2 | PFS | 2.497 months |
| Erlotinib, Gemcitabine: Rash Grade ≥ 2 | PFS | 6.439 months |