Pancreatic Cancer, Resected
Conditions
Keywords
Pancreatic cancer, resected, Vaccine, KRAS
Brief summary
The purpose of this study is to investigate the effect of TG01 and Granulocyte macrophage colony stimulating factor (GM-CSF) when given in addition to gemcitabine (chemotherapy) and * Understand any possible side effects of the additional use of TG01/GM-CSF with gemcitabine * Investigate whether TG01/GM-CSF when given with gemcitabine can produce an immune response * Investigate if the treatment can delay or reduce recurrence of the disease
Interventions
BIOLOGICALTG01
TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes
Sponsors
Targovax ASA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas 2. Stage I or II disease (clinical stage T1-3, N0-1, M0 by AJCC staging criteria). 3. Successful surgical resection * Complete resection (R0) or with microscopic residual disease (R1) * Expected to receive gemcitabine monotherapy as adjuvant chemotherapy 4. Laboratory Values: * Absolute neutrophil count ≥ 1.5 x 10\^9/l * Platelets ≥100 x 10\^9/l * Haemoglobin ≥ 9 g/dl * Total bilirubin ≤ 1.5 x UNL * Serum creatinine ≤ 1.5 x UNL * Albumin ≥ 2.5 g/dl * AST or ALT ≥ 5 x UNL 5. 18 years of age or older. 6. ECOG performance status (PS) of 0-1. 7. Life expectancy of at least 6 months 8. Men and women of childbearing potential must be willing to use effective methods of contraception to prevent pregnancy 9. Provide written (signed) informed consent to participate in the trial prior to any trial specific screening procedures
Exclusion criteria
1. Has received an investigational drug within 4 weeks prior to Trial drug administration 2. Has received previous therapy for pancreatic cancer including radiation or chemotherapy (except for the primary resection or primary neoadjuvant chemotherapy). 3. Is currently receiving any agent with a known effect on the immune system, unless at dose levels that are not immunosuppressive (e.g. Prednisone at 10 mg/day or less or as inhaled steroid at doses used for the treatment of asthma). 4. Has any other serious illnesses or medical conditions such as, but not limited to: * Any uncontrolled infection * Uncontrolled cardiac failure classification III or IV (NY Heart Association) * Uncontrolled systemic and gastro-intestinal inflammatory conditions * Bone marrow dysplasia * History of auto-immune disease * History of adverse reactions to vaccines 5. Known history of positive tests for HIV/AIDS, hepatitis B or C 6. Pregnant or lactating females or have no pregnancy test at baseline (postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential). 7. Contraindication to gemcitabine treatment 8. Have had any other malignancies within last 3 years (except for adequately treated carcinoma of the cervix or basal or squamous cell skin cancer) 9. Known malignant brain lesion(s) 10. Are unlikely to start chemotherapy within 12 weeks of surgery (e.g. delayed wound healing, or infection, etc.) 11. Are not expected to complete 6 cycles of chemotherapy 12. Are planned to receive yellow fever or other live (attenuated) vaccines during the course of study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients' Safety During Study | 2 years | Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI |
| Patients' Immune Response | During the 2 years of treatment | Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy | DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years. | Efficacy exploring disease free survival and overall survival. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relationship Between (KRAS) Status and Clinical Efficacy | 2 years | Relationship between KRAS status and recurrence |
Countries
Norway, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TG01/GM-CSF and Gemcitabine TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | TG01/GM-CSF and Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 64.1 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment Norway | 11 participants |
| Region of Enrollment United Kingdom | 21 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 32 |
| other Total, other adverse events | 16 / 32 |
| serious Total, serious adverse events | 3 / 32 |
Outcome results
Primary
Patients' Immune Response
Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment
Time frame: During the 2 years of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TG01/GM-CSF and Gemcitabine | Patients' Immune Response | 94 percentage of patients |
Primary
Patients' Safety During Study
Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TG01/GM-CSF and Gemcitabine | Patients' Safety During Study | AEs related to TG01 and/or GM-CSF | 90 Events related to TG01 and /or GM-CSF |
| TG01/GM-CSF and Gemcitabine | Patients' Safety During Study | SAEs related to TG01 and/or GM-CSF | 2 Events related to TG01 and /or GM-CSF |
Secondary
Clinical Efficacy
Efficacy exploring disease free survival and overall survival.
Time frame: DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TG01/GM-CSF and Gemcitabine | Clinical Efficacy | Overall survival | 33.3 Months |
| TG01/GM-CSF and Gemcitabine | Clinical Efficacy | Disease free survival | 16.1 Months |
Other Pre-specified
Relationship Between (KRAS) Status and Clinical Efficacy
Relationship between KRAS status and recurrence
Time frame: 2 years
Population: As the majority of the patients (26 of 32) patients had a KRAS mutation detected, it was not possible to accurately assess relationship between KRAS status and survival outcomes.