RECRUITING

Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells. The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

Official Title

A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating Neoadjuvant Therapy Targeting the Adenosine Immunosuppressive Pathway in Combination With Immune Checkpoint Blockade and Radiation Therapy in Patients With Advanced PANCreatic Ductal Adenocarcinoma Who Are Candidates for Surgical Resection

Quick Facts

Study Start:2024-06

Study Completion:2027-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06048484

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of pancreatic ductal adenocarcinoma (PDAC) needs to be verified by the treating institution pathologist. A pathological report from non-treating institutions is sufficient to consent and to initiate investigational therapy if tissue sample is unavailable for evaluation at time of consent or enrollment. However, in such a case, PDAC diagnosis should be confirmed by the treating institution pathologist at a later time. * Completed 8 cycles of neoadjuvant modified FOLFIRINOX. Omission of oxaliplatin due to adverse events may be allowed in cycles 5-8 with consultation with the principal investigator. * Patients with surgically resectable PDAC who are considered appropriate to undergo the applicable operation. * Eligible to undergo SBRT. * Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * No prior surgical, systemic, or radiotherapy for PDAC except for mFOLFIRINOX. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Age ≥ 18 years. * Adequate hematological and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of investigational treatment:	* Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies. * Patients who are receiving any other investigational agents concurrently. * Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable). * Uncontrolled pleural effusion, pericardial effusion, or ascites. * Uncontrolled hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL, or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. * Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (some exceptions permissible as outlined per protocol). * History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. * Positive HIV test at screening or at any time prior to screening. * Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening. * Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. * Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease, and inherited liver disease. * Known active tuberculosis. * Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications. * Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents and breastfeeding should be discontinued. * History of allergy or hypersensitivity to oxaliplatin, irinotecan, leucovorin, fluorouracil, pegfilgrastim, or any excipients. * History of Gilbert's disease or known genotype UGT1A1 \28/\28. * Inflammatory disease of the colon or rectum, or severe uncontrolled diarrhea. * Active or history of celiac disease. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Inclusion Criteria

Exclusion Criteria

* Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of pancreatic ductal adenocarcinoma (PDAC) needs to be verified by the treating institution pathologist. A pathological report from non-treating institutions is sufficient to consent and to initiate investigational therapy if tissue sample is unavailable for evaluation at time of consent or enrollment. However, in such a case, PDAC diagnosis should be confirmed by the treating institution pathologist at a later time.
* Completed 8 cycles of neoadjuvant modified FOLFIRINOX. Omission of oxaliplatin due to adverse events may be allowed in cycles 5-8 with consultation with the principal investigator.
* Patients with surgically resectable PDAC who are considered appropriate to undergo the applicable operation.
* Eligible to undergo SBRT.
* Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* No prior surgical, systemic, or radiotherapy for PDAC except for mFOLFIRINOX.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Age ≥ 18 years.
* Adequate hematological and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of investigational treatment:

* Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
* Patients who are receiving any other investigational agents concurrently.
* Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable).
* Uncontrolled pleural effusion, pericardial effusion, or ascites.
* Uncontrolled hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL, or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
* Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (some exceptions permissible as outlined per protocol).
* History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
* Positive HIV test at screening or at any time prior to screening.
* Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
* Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
* Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease, and inherited liver disease.
* Known active tuberculosis.
* Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications.
* Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents and breastfeeding should be discontinued.
* History of allergy or hypersensitivity to oxaliplatin, irinotecan, leucovorin, fluorouracil, pegfilgrastim, or any excipients.
* History of Gilbert's disease or known genotype UGT1A1 \*28/\*28.
* Inflammatory disease of the colon or rectum, or severe uncontrolled diarrhea.
* Active or history of celiac disease.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Contacts and Locations

Study Contact

Research Nurse Navigator

CONTACT

212-342-5162

cancerclinicaltrials@cumc.columbia.edu

Principal Investigator

Gulam Manji, MD, PhD

PRINCIPAL_INVESTIGATOR

Columbia University

Study Locations (Sites)

Columbia University Irving Medical Center

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Gulam Manji

Gulam Manji, MD, PhD, PRINCIPAL_INVESTIGATOR, Columbia University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06

Study Completion Date2027-04

Study Record Updates

Study Start Date2024-06

Study Completion Date2027-04

Terms related to this study

Additional Relevant MeSH Terms

Pancreatic Ductal Adenocarcinoma