Clinical trial NCT05014776: Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer
Official title: A Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: Pancreatic cancer
Pembrolizumab
Ipilimumab
CRS-207
Tadalafil
Immunotherapy
Anti-PD-1
Anti-CTLA-4
Adenocarcinoma
Carcinoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Lustgarten Foundation
name: National Cancer Institute (NCI)
First posted: 2021-08-20
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
timeFrame: 9 months
Secondary outcomes:
measure: Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation
timeFrame: 9 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institution
name: Katherine Bever, MD
role: PRINCIPAL_INVESTIGATOR
References: