The purpose of this study is to find out if an experimental drug will prevent metastatic pancreatic adenocarcinoma from becoming resistant to standard treatment for the disease. The names of the study drugs involved in this study are: * 9-ING-41 * Losartan * Ferumoxytol * FOLFIRINOX (made up of 4 different drugs): * 5-Fluorouracil (5-FU) * Oxaliplatin * Irinotecan * Leucovorin
This is a multi-institutional, open label, four-arm, non-comparator Phase 2 study of FOLFIRINOX in combination with 9-ING-41 and losartan for the treatment of adult patients with untreated metastatic pancreatic adenocarcinoma (PAC). This research study will begin with a Safety Run-In phase. The Safety Run-In phase will establish the side effects from the study treatment to its safety before beginning the main part of the study. Once that is complete, the main portion of the study will be a Phase II clinical trial. The U.S. Food and Drug Administration (FDA) has not approved 9-ING-41 as a treatment for pancreatic adenocarcinoma (PAC). The FDA has not approved Losartan for pancreatic adenocarcinoma (PAC), but it has been approved for other uses. The FDA has approved FOLFIRINOX as a treatment option for pancreatic adenocarcinoma (PAC). This research study involves giving participants an investigational drug called 9- ING-41 with standard anti-cancer drugs. 9-ING-41 stops an enzyme called GSK- 3β from working in cancer cells. Enzymes are proteins that activate and accelerate chemical reactions. The GSK-3β enzyme helps cancer cells to grow and to become resistant to chemotherapy drugs. This study is trying to see if by stopping the activity of GSK-3β using 9-ING-41, it may be possible for standard of care chemotherapy drugs to regain their effectiveness in treating cancers in participants where they have stopped being effective or are effective in only a minority of participants. FOLFIRINOX is a combination of 4 chemotherapy agents that may help shrink pancreatic adenocarcinoma (PAC) tumors. Losartan is a drug that is used to lower blood pressure. In this setting, Losartan has also been demonstrated to suppress TGF-β function in pancreatic adenocarcinoma. Cytokines are molecules that help cells communicate and play a role in immune response. Suppression of TGF-β function is believed to stop the cancer cells from becoming resistant to chemotherapy. This study will evaluate if blocking of GSK-3β activity using 9-ING-41 and blocking of TGF-β function using Losartan can inhibit cancer cell resistance to FOLFIRINOX chemotherapy. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Participants will receive treatment during three portions of the study: Complete therapy, Maintenance therapy and Transition to complete therapy. After treatment, participants will be followed for up to 5 years. It is expected that up to 70 people will take part in this research study. Actuate Therapeutics, a pharmaceutical company, is supporting this research study by providing the study drug 9-ING-41. The Lustgarten Foundation is providing funding support for this study through a research grant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Combination of 4 different drugs (5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan and Leucovorin) administered by intravenous infusion
Taken Orally
Administered by intravenous infusion
University of Colorado Cancer Center
Aurora, Colorado, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Charlestown, Massachusetts, United States
University of Washington School of Medicine
Seattle, Washington, United States
Progression-free survival (PFS)
Defined from the date of study entry to the earliest date of progressive disease while receiving complete therapy with FOLFIRINOX-based therapy or death due to any cause. PFS will be censored at the date of last follow-up for patients alive without documented progression. PFS curves will be estimated by the Kaplan-Meier method and compared to historical controls treated with FOLFIRINOX alone using the one-sample log-rank test.
Time frame: Date of study entry to the earliest date of progressive disease up to 30 months
Overall survival (OS)
Defined from the date of study entry to the date of death due to any cause and censored at the date of last follow-up for patients still alive. OS curves will be estimated by the Kaplan-Meier method and compared to historical controls using the one-sample log-rank test.
Time frame: Up to 30 months
Median time of maintenance therapy (mMT):
Defined from the date of starting maintenance 5FU-based therapy to time of objective disease progression.
Time frame: Up to 30 months
Objective Response Rate
Defined as the proportion of patients who have a partial or complete response per RECIST 1.1 criteria
Time frame: Up to 30 months
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