Pancreatic Cancer
Conditions
Brief summary
This open-label, single-arm, multicenter trial is designed to evaluate the safety of erlotinib in combination with standard of care chemotherapy (gemcitabine) in participants with locally advanced, unresectable, or metastatic pancreatic cancer.
Interventions
DRUGErlotinib
Participants will receive erlotinib tablets as 100 milligrams (mg) orally (PO) once daily.
DRUGGemcitabine
Participants will receive gemcitabine as 1000 milligrams per meter-squared (mg/m\^2) via intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36, and 43 of the first 8-week cycle, and thereafter on Days 1, 8, and 15 of every 4-week cycle.
Sponsors
Hoffmann-La Roche
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
* Histologically or cytologically confirmed adenocarcinoma with locally advanced, unresectable, or metastatic disease * No prior systemic treatment for metastatic disease * Adjuvant therapy ≥6 months prior to study entry with no residual toxic effects * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3 * Life expectancy ≥12 weeks * Adequate hematologic, hepatic, and renal function * Negative pregnancy test within 72 hours of study drug and use of effective contraception among women of childbearing potential
Exclusion criteria
* Unstable systemic disease * Prior systemic human epidermal growth factor receptor 1 (HER1) or epidermal growth factor receptor (EGFR) inhibitors * Other malignancy within 5 years prior to study entry * Significant opthalmologic abnormality * Inability to take oral medication * Need for IV alimentation * Prior surgery affecting absorption * Active peptic ulcer disease * Nursing mothers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 40 months (assessed continuously during treatment) | An AE was defined as any untoward medical occurrence and which did not necessarily have a causal relationship with treatment. The percentage of participants who experienced at least 1 AE was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Up to approximately 40 months (assessed at Baseline, every 4 weeks during treatment, and end of study) | The QLQ-C30 is a 30-item questionnaire that assesses physical (Questions 1-5), role (Questions 6-7), emotional (Questions 21-24), cognitive (Questions 20 and 25), and social (Questions 26-27) functional domains as well as global health status (Questions 29-30) and several symptoms including fatigue (Questions 10, 12, and 18), pain (Questions 9 and 19), nausea/vomiting (Questions 14-15), dyspnea (Question 8), appetite loss (Question 13), insomnia (Question 11), constipation/diarrhea (Questions 16-17), and financial difficulties (Question 28). Questions 1 to 28 were assessed on a 4-point scale from 1 (no/not at all) to 4 (very much) where higher scores represented worse symptoms. Questions 29 and 30 were assessed on a 7-point scale from 1 (very poor) to 7 (excellent) where higher scores represented better functioning. Item scores over the study period were averaged among all participants across all visits for which data were available. |
| Percentage of Participants Who Died | Up to approximately 40 months (assessed continuously through end of study) | The percentage of participants who died from any cause was reported to the nearest integer. |
| Overall Survival (OS) | Up to approximately 40 months (assessed continuously through end of study) | OS was defined as the time from start of treatment to time of death from any cause. Participants who had not died at the time of final analysis were censored at the date of last contact. OS was estimated by Kaplan-Meier methodology and expressed in months. |
| Percentage of Participants With Death or Disease Progression According to Response Evaluation Criteria in Solid Tumors (RECIST) | Up to approximately 40 months (assessed at Baseline, every 8 weeks during treatment, and end of study) | Tumor assessments were performed using RECIST. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of longest diameters (LD) of target lesions in reference to smallest sum of LD on study. The percentage of participants who died or demonstrated disease progression was reported to the nearest integer. |
| Progression-Free Survival (PFS) According to RECIST | Up to approximately 40 months (assessed at Baseline, every 8 weeks during treatment, and end of study) | Tumor assessments were performed using RECIST. PFS was defined as the time from treatment start to the time of death or disease progression. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum of LD on study. PFS was estimated by Kaplan-Meier methodology and expressed in months. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib + Gemcitabine Participants with locally advanced, unresectable, or metastatic pancreatic cancer received erlotinib in combination with standard of care chemotherapy (gemcitabine) until disease progression, unacceptable toxicity, or withdrawal for any reason. Erlotinib was administered as 100 mg PO once daily. Gemcitabine was administered as 1000 mg/m\^2 via IV infusion on Days 1, 8, 15, 22, 29, 36, and 43 of the first 8-week cycle, and thereafter on Days 1, 8, and 15 of every 4-week cycle. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 8 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 22 |
| Overall Study | Progressive Disease | 40 |
| Overall Study | Study Drug-Related Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Erlotinib + Gemcitabine |
|---|---|
| Age, Continuous | 62.45 years STANDARD_DEVIATION 10.299 |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 80 |
| serious Total, serious adverse events | 35 / 80 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence and which did not necessarily have a causal relationship with treatment. The percentage of participants who experienced at least 1 AE was reported.
Time frame: Up to approximately 40 months (assessed continuously during treatment)
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Gemcitabine | Percentage of Participants With Adverse Events (AEs) | 78.8 percentage of participants |
Secondary
European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores
The QLQ-C30 is a 30-item questionnaire that assesses physical (Questions 1-5), role (Questions 6-7), emotional (Questions 21-24), cognitive (Questions 20 and 25), and social (Questions 26-27) functional domains as well as global health status (Questions 29-30) and several symptoms including fatigue (Questions 10, 12, and 18), pain (Questions 9 and 19), nausea/vomiting (Questions 14-15), dyspnea (Question 8), appetite loss (Question 13), insomnia (Question 11), constipation/diarrhea (Questions 16-17), and financial difficulties (Question 28). Questions 1 to 28 were assessed on a 4-point scale from 1 (no/not at all) to 4 (very much) where higher scores represented worse symptoms. Questions 29 and 30 were assessed on a 7-point scale from 1 (very poor) to 7 (excellent) where higher scores represented better functioning. Item scores over the study period were averaged among all participants across all visits for which data were available.
Time frame: Up to approximately 40 months (assessed at Baseline, every 4 weeks during treatment, and end of study)
Population: Safety Population. The Number of Participants Analyzed reflects the total number of participants who contributed to the endpoint. The number of responses for each questionnaire item combined across all assessments (n) is shown in the table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q1: Trouble in strenuous activities (n=256) | 1.96 units on a scale | Standard Deviation 0.758 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q2: Trouble with long walk (n=259) | 2.03 units on a scale | Standard Deviation 0.802 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q3: Trouble with short walk (n=258) | 1.50 units on a scale | Standard Deviation 0.696 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q4: Need to say in bed or chair (n=255) | 1.87 units on a scale | Standard Deviation 0.699 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q5: Need help in daily activities (n=259) | 1.21 units on a scale | Standard Deviation 0.501 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q6: Limited in doing work/daily activities (n=257) | 1.82 units on a scale | Standard Deviation 0.803 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q7: Limited in pursuing hobbies (n=255) | 1.73 units on a scale | Standard Deviation 0.798 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q8: Short of breath (n=258) | 1.38 units on a scale | Standard Deviation 0.608 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q9: Pain (n=257) | 1.88 units on a scale | Standard Deviation 0.771 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q10: Need to rest (n=255) | 2.05 units on a scale | Standard Deviation 0.697 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q11: Trouble sleeping (n=257) | 1.74 units on a scale | Standard Deviation 0.699 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q12: Felt weak (n=255) | 2.05 units on a scale | Standard Deviation 0.774 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q13: Lacked appetite (n=257) | 1.70 units on a scale | Standard Deviation 0.73 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q14: Felt nauseated (n=257) | 1.48 units on a scale | Standard Deviation 0.679 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q15: Vomited (n=259) | 1.10 units on a scale | Standard Deviation 0.414 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q16: Constipated (n=259) | 1.51 units on a scale | Standard Deviation 0.723 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q17: Diarrhea (n=259) | 1.27 units on a scale | Standard Deviation 0.496 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q18: Tired (n=255) | 2.07 units on a scale | Standard Deviation 0.689 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q19: Pain interference with daily activity (n=256) | 1.69 units on a scale | Standard Deviation 0.814 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q20: Difficulty concentrating (n=257) | 1.49 units on a scale | Standard Deviation 0.638 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q21: Felt tense (n=256) | 1.97 units on a scale | Standard Deviation 0.716 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q22: Worried (n=253) | 2.10 units on a scale | Standard Deviation 0.773 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q23: Felt irritable (n=258) | 1.75 units on a scale | Standard Deviation 0.707 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q24: Felt depressed (n=258) | 1.67 units on a scale | Standard Deviation 0.658 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q25: Difficulty remembering things (n=257) | 1.44 units on a scale | Standard Deviation 0.543 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q26: Interference with family life (n=257) | 1.59 units on a scale | Standard Deviation 0.68 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q27: Interference with social activities (n=257) | 1.62 units on a scale | Standard Deviation 0.772 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q28: Financial difficulties (n=258) | 1.32 units on a scale | Standard Deviation 0.655 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q29: Overall health (n=255) | 4.44 units on a scale | Standard Deviation 1.314 |
| Erlotinib + Gemcitabine | European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Item Scores | Q30: Overall quality of life (n=255) | 4.38 units on a scale | Standard Deviation 1.346 |
Secondary
Overall Survival (OS)
OS was defined as the time from start of treatment to time of death from any cause. Participants who had not died at the time of final analysis were censored at the date of last contact. OS was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Up to approximately 40 months (assessed continuously through end of study)
Population: Safety Population. The Number of Participants Analyzed reflects the number of participants who contributed to the endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Gemcitabine | Overall Survival (OS) | 7.49 months |
Secondary
Percentage of Participants Who Died
The percentage of participants who died from any cause was reported to the nearest integer.
Time frame: Up to approximately 40 months (assessed continuously through end of study)
Population: Safety Population. The Number of Participants Analyzed reflects the number of participants who contributed to the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Gemcitabine | Percentage of Participants Who Died | 73 percentage of participants |
Secondary
Percentage of Participants With Death or Disease Progression According to Response Evaluation Criteria in Solid Tumors (RECIST)
Tumor assessments were performed using RECIST. Disease progression was defined as greater than or equal to (≥) 20 percent (%) increase in sum of longest diameters (LD) of target lesions in reference to smallest sum of LD on study. The percentage of participants who died or demonstrated disease progression was reported to the nearest integer.
Time frame: Up to approximately 40 months (assessed at Baseline, every 8 weeks during treatment, and end of study)
Population: Safety Population. The Number of Participants Analyzed reflects the number of participants who contributed to the endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib + Gemcitabine | Percentage of Participants With Death or Disease Progression According to Response Evaluation Criteria in Solid Tumors (RECIST) | 88 percentage of participants |
Secondary
Progression-Free Survival (PFS) According to RECIST
Tumor assessments were performed using RECIST. PFS was defined as the time from treatment start to the time of death or disease progression. Disease progression was defined as ≥20% increase in sum of LD of target lesions in reference to smallest sum of LD on study. PFS was estimated by Kaplan-Meier methodology and expressed in months.
Time frame: Up to approximately 40 months (assessed at Baseline, every 8 weeks during treatment, and end of study)
Population: Safety Population. The Number of Participants Analyzed reflects the number of participants who contributed to the endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib + Gemcitabine | Progression-Free Survival (PFS) According to RECIST | 4.864 months |