Pancreatic Cancer
Conditions
Keywords
Pancreatic cancer, Pembrolizumab, Ipilimumab, CRS-207, Tadalafil, Immunotherapy, Anti-PD-1, Anti-CTLA-4, Adenocarcinoma, Carcinoma
Brief summary
The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects with metastatic pancreatic adenocarcinoma who have progressed after at least 1 prior chemotherapy regimen.
Interventions
DRUGTadalafil
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Tadalafil (20 mg) will be administered orally every day on days 3-21 for cycles 1-6.
DRUGPembrolizumab
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on Day 1 of cycles 1-6.
DRUGIpilimumab
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (50mg) will be administered IV on Day 1 of Cycles 1, 3, and 5.
DRUGCRS-207
Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 \[1 × 10\^9 colony forming units (CFU) in 100ml NS\] will be administered IV on Day 2 of Cycles 1-6.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lustgarten Foundation
National Cancer Institute (NCI)
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
* Age ≥18 years. * Have histologically or cytologically proven adenocarcinoma of the pancreas. * Have previously treated metastatic disease. * Have radiographic disease progression. * Patients with the presence of at least one measurable tumor lesion. * Patient's acceptance to have a tumor biopsy at baseline and on * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Patients must have adequate organ and marrow function defined by study-specified laboratory tests. * For both Women and Men, must use acceptable form of birth control while on study. * Ability to understand and willingness to sign a written informed consent document.
Exclusion criteria
* Known history or evidence of brain metastases. * Had chemotherapy, radiation, or biological cancer therapy within the last 14 days. * Have received an investigational agent or device within the last 28 days. * Had surgery within the last 28 days. * Expected to require any other form of systemic or localized cancer therapy while on study. * Have received a vaccine within the last 14 days (7 days for the COVID vaccine) or received a live vaccine within the last 30 days. * Have received steroids within the last 14 days. * Use more than 4 g/day of acetaminophen. * Use of organic nitrates. * Use of guanylate cyclase (GC) stimulators such as riociguat. * Consumption of substantial amounts of alcohol (≥5 units/day) * Use of strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. * Patients on immunosuppressive agents within the last 7 days * Known allergy to both penicillin and sulfa. * Severe hypersensitivity reaction to any monoclonal antibody. * History of severe hypersensitivity to tadalafil. * Have implant(s) or device(s) that has not and cannot be easily removed. * Have artificial joints or implanted medical devices that cannot be easily removed. * Have any evidence of clinical or radiographic ascites. * Have significant and/or malignant pleural effusion * Uncontrolled intercurrent illness. * Subjects with active, known or suspected autoimmune disease. * Have a tissue or organ allograft, including corneal allograft. * Have been diagnosed HIV, Hepatitis B or C positive. * Is on supplemental home oxygen. * Has an unhealed surgical wound or ulcer, or a bone fracture considered non-healing. * Has clinically significant heart disease * Prior history of non-arterial ischemic optic retinopathy. * History of significant hypotensive episode requiring hospitalization within 6 months. * Has insufficient peripheral vein access. * Is unwilling or unable to follow the study schedule for any reason. * Is pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) | 9 months | Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 9 months |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKatherine Bever, MD
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institution
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207 Tadalafil: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Tadalafil (20 mg) will be administered orally every day on days 3-21 for cycles 1-6.
Pembrolizumab: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on Day 1 of cycles 1-6.
Ipilimumab: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (50mg) will be administered IV on Day 1 of Cycles 1, 3, and 5.
CRS-207: Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 \[1 × 10\^9 colony forming units (CFU) in 100ml NS\] will be administered IV on Day 2 of Cycles 1-6. | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 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 | 9 Participants |
| Region of Enrollment United States | 17 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 17 |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 12 / 17 |
Outcome results
Primary
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207 | Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) | 0 Participants |
Secondary
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207 | Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation | 0 Participants |