CENDIFOX: CEND-1 in Combination With Neoadjuvant FOLFIRINOX With or Without Panitumumab

Sponsor

Anup Kasi (Other)

Overall Status

Recruiting

CT.gov ID

NCT05121038

Collaborator

Cend Therapeutics Inc. (Other)

Enrollment

Locations

Arms

46.4

Anticipated Duration (Months)

16.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase IB/IIA trial to ensure the safety of CEND-1 in combination with with Folfirinox with or without Panitumumab for treatment of pancreatic, colon and appendiceal cancers

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer Pancreas Cancer Digestive Cancer	Drug: CEND-1 Drug: Panitumumab Drug: Folfirinox	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1B/2A Trial Of CEND-1 In Combination With Neoadjuvant FOLFIRINOX Based Therapies In Pancreatic, Colon And Appendiceal Cancers (CENDIFOX)

Actual Study Start Date :

Oct 20, 2021

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Pancreatic Cancer Biopsy for tissue immune profile if archived tissue not available. Folfirinox infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus CEND1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.	Drug: CEND-1 The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4). Drug: Folfirinox FOLFIRINOX is a name for a chemotherapy treatment regimen that includes several different drugs that are given in a certain order. All of these drugs are given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle). Oxaliplatin - dose is 85 mg / m2 the infusion takes about 2 hours. then Leucovorin - dose is 400 mg / m2 - this is given at same time with irinotecan (below) and the infusion takes about 1.5 hours. Irinotecan - dose is 180 mg / m2 - this is given at same time with leucovorin (above), and the infusion takes about 1.5 hours. then • Fluorouracil - dose is 2400 mg / m2 - this infusion takes 46 to 48 hours (2 days) with an IV pump done at home. Other Names: Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil
Experimental: Cohort 2 Peritoneal Mets Biopsy for tissue immune profile if archived tissue not available. Folfirinox plus Panitumumab (if RAS/BRAF) infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus Panitumumab (if RAS/BRAF positive) and CEND1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.	Drug: CEND-1 The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4). Drug: Panitumumab Up to ten (10) participants with cancer that has spread to certain areas of the body and who have a certain gene in the tumor called "RAS/BRAF wild type" will receive another drug called panitumumab in addition to CEND-1 and FOLFIRINOX. Drug: Folfirinox FOLFIRINOX is a name for a chemotherapy treatment regimen that includes several different drugs that are given in a certain order. All of these drugs are given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle). Oxaliplatin - dose is 85 mg / m2 the infusion takes about 2 hours. then Leucovorin - dose is 400 mg / m2 - this is given at same time with irinotecan (below) and the infusion takes about 1.5 hours. Irinotecan - dose is 180 mg / m2 - this is given at same time with leucovorin (above), and the infusion takes about 1.5 hours. then • Fluorouracil - dose is 2400 mg / m2 - this infusion takes 46 to 48 hours (2 days) with an IV pump done at home. Other Names: Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil
Experimental: Cohort 3 Oligomets Colon Cancer Biopsy for tissue immune profile if archived tissue not available. Folfirinox plus Panitumumab (if RAS/BRAF) infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus Panitumumab (if RAS/BRAF positive) and CEND1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.	Drug: CEND-1 The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4). Drug: Panitumumab Up to ten (10) participants with cancer that has spread to certain areas of the body and who have a certain gene in the tumor called "RAS/BRAF wild type" will receive another drug called panitumumab in addition to CEND-1 and FOLFIRINOX. Drug: Folfirinox FOLFIRINOX is a name for a chemotherapy treatment regimen that includes several different drugs that are given in a certain order. All of these drugs are given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle). Oxaliplatin - dose is 85 mg / m2 the infusion takes about 2 hours. then Leucovorin - dose is 400 mg / m2 - this is given at same time with irinotecan (below) and the infusion takes about 1.5 hours. Irinotecan - dose is 180 mg / m2 - this is given at same time with leucovorin (above), and the infusion takes about 1.5 hours. then • Fluorouracil - dose is 2400 mg / m2 - this infusion takes 46 to 48 hours (2 days) with an IV pump done at home. Other Names: Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil

Arm

Intervention/Treatment

Experimental: Cohort 1 Pancreatic Cancer

Biopsy for tissue immune profile if archived tissue not available. Folfirinox infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus CEND1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.

Drug: CEND-1

The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4).

Drug: Folfirinox

FOLFIRINOX is a name for a chemotherapy treatment regimen that includes several different drugs that are given in a certain order. All of these drugs are given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle). Oxaliplatin - dose is 85 mg / m2 the infusion takes about 2 hours. then Leucovorin - dose is 400 mg / m2 - this is given at same time with irinotecan (below) and the infusion takes about 1.5 hours. Irinotecan - dose is 180 mg / m2 - this is given at same time with leucovorin (above), and the infusion takes about 1.5 hours. then • Fluorouracil - dose is 2400 mg / m2 - this infusion takes 46 to 48 hours (2 days) with an IV pump done at home.

Other Names:

Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil

Experimental: Cohort 2 Peritoneal Mets

Biopsy for tissue immune profile if archived tissue not available. Folfirinox plus Panitumumab (if RAS/BRAF) infusion for 3 cycles followed by a repeat biopsy for a second tissue immune profiling. Folfirinox plus Panitumumab (if RAS/BRAF positive) and CEND1 infusion for 3 cycles. Seventy-two hours after last infusion participant will have surgery.

Drug: CEND-1

The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4).

Drug: Panitumumab

Up to ten (10) participants with cancer that has spread to certain areas of the body and who have a certain gene in the tumor called "RAS/BRAF wild type" will receive another drug called panitumumab in addition to CEND-1 and FOLFIRINOX.

Drug: Folfirinox

Other Names:

Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil

Experimental: Cohort 3 Oligomets Colon Cancer

Drug: CEND-1

The treatment with CEND-1 will be given as an intravenous (IV) infusion (through a needle in a vein) at the clinic once every 14 days (or Day 1 of every 14-day cycle starting in Cycle 4).

Drug: Panitumumab

Drug: Folfirinox

Other Names:

Oxaliplatin,Leucovorin,Irinotecan,Fluorouracil

Outcome Measures

Primary Outcome Measures

Drug Safety: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [24 months]
Adverse Events : Counts and proportions of grade 3 -5 Adverse Events

Secondary Outcome Measures

Overall survival (OS) [48 months]
Overall survival (OS) will be reported using median survival time along with a 90% confidence interval
Disease-free survival (DFS) [48 months]
Disease-free survival (DFS) will be reported using median survival time along with a 90% confidence interval
Overall response rate (ORR) [24 months]
Overall response rate (ORR) will be reported as a proportion with 90% confidence interval.
RO resection rate (RORR) [24 months]
RO resection rate (RORR) will be reported as a proportion with 90% confidence interval.
Pathological response rate (PCR) . [24 months]
Pathological response rate (PCR) will be reported as a proportion with 90% confidence interval.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
One or more lesions evaluable on MRI, positive emission tomography (PET)/CT, or dedicated CT scan according to RECIST v1.1
Patients with histologically confirmed pancreatic ductal adenocarcinomas, colorectal and appendiceal adenocarcinomas
For cohort 1: Resectable Pancreatic Cancer: No evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery. There must be clear fat plane between SMA and celiac axis. Patent superior mesenteric vein (SMV/portal vein (PV) with no distortion of venous architecture. Please refer to 2021 NCCN PDAC Guidelines
For cohort 1: Borderline Resectable Pancreatic Cancer: defined as localized cancer with 1 or more of the following features: "a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180o or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180o of the circumference of the artery wall. Please refer to 2021 National Comprehensive Cancer Network (NCCN) Pancreatic Ductal Adenocarcinoma (PDAC) Guidelines
For cohort 2: Peritoneal Metastases due to Colorectal Cancer or Invasive Adenocarcinoma of the Appendix
For cohort 3: Oligometastatic colorectal cancer: resectable metastases as determined by multidisciplinary evaluation. Patients with bilobar liver metastases or oligometastatic liver and lung metastases that requires resection of one or more metastases are also allowed
Eligible for treatment with FOLFIRINOX with or without panitumumab
Life expectancy of at least 3 months
Adequate archival tissue from prior biopsy for biomarker evaluation or willingness to undergo biopsy before treatment starts and on treatment
Medically fit to undergo complex major abdominal surgery at end of study treatment
Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to enrollment
Adequate organ function

Exclusion Criteria:

Simultaneously enrolled in any therapeutic clinical trial
Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents
Prior chemotherapy or any other investigational agents for the treatment of cancer within 2 years prior to enrollment on this study
Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
Is pregnant or breastfeeding
Has a known allergic reaction to any excipient contained in the study drug formulation
Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
Known infection with HIV, hepatitis B, or hepatitis C
Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator
Participants with known brain metastases. Screening for brain metastases with head imaging is not required
History of prior or current synchronous malignancy, except:
Malignancy that was treated with curative intent and for which there has been no known active disease for >3 years prior to enrollment
Curatively treated non-melanoma skin cancer, cervical cancer in situ, or prostatic intraepithelial neoplasia, without evidence of prostate cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Kansas Cancer Center (KUCC)	Fairway	Kansas	United States	66205
2	The University of Kansas Cancer Center, Westwood Campus	Kansas City	Kansas	United States	66205
3	The University of Kansas Medical Center	North Kansas City	Missouri	United States	64116