A Phase I Trial of ProAgio, an Anti- Alpha-v-beta3 Integrin Cytotoxin, for Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies

Pancreatic Cancer Clinical Trial

Official title: A Phase I Trial of ProAgio, an Anti- Alpha-v-beta3 Integrin Cytotoxin, for Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies

Status Not yet recruiting

Clinical Trial Summary

Background:

• Pancreatic cancer is the third leading cause of death from cancer in the United States.

• The median overall survival for patients with metastatic disease and excellent performance status receiving the most effective combination chemotherapy regimens remains less than 1 year

• Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer histology, is surrounded by a dense desmoplastic stromal reaction generated by cross-talk between tumor cells and the cancer associated stellate cells (CASC) and fibroblasts (CAF) in the microenvironment.

• This stroma physically inhibits delivery of therapeutic drugs to tumor cells, secretes growth factors and nutrients that promote therapy resistance and cancer cell survival and is also highly immunosuppressive

• Activated CASCs, CAFs and angiogenic endothelial cells which form the abnormal vasculature around tumors, all express high levels of integrin vbeta3.

• ProAgio is a rationally designed pegylated peptide drug that binds to integrin vbeta3 at a novel binding site that directly triggers cell apoptosis

• ProAgio induces apoptosis of CASCs and angiogenic endothelial cells in pre-clinical models, inhibiting tumor growth and prolonging animal survival

• Safety of ProAgio in rodent and non-human primate models has been established

• ProAgio has never been tested in humans

Primary Objectives:

To determine the recommended phase 2 dose (RP2D) of ProAgio in participants with previously treated advanced solid tumors for which no curative therapy exists

Eligibility:

• Adults >= 18 years of age

• Histologically confirmed solid tumor malignancy for which no curative therapy exists as confirmed by the NCI Laboratory of Pathology

• For the expansion cohort only: Histologically confirmed diagnosis of pancreatic cancer that is not neuroendocrine

• Participants must have received at least one prior systemic treatment

• Adequate end organ function is required

• Participants in the Biopsy Arm of the expansion cohort must have disease amenable to safe biopsy and willingness to undergo the procedure

Design:

• This is a Phase I study to assess the safety of ProAgio in Participants with advanced solid tumor malignancies including pancreatic cancer

• All participants will receive ProAgio until disease progression, unacceptable toxicity, or withdrawal from study

• For the dose escalation cohort, a modified 3+3 design with accelerated dose escalation in initial cohorts will be used

• For the expansion cohort, all participants will receive ProAgio at the ideal dose identified during the dose escalation

• The expansion cohort has two arms: standard arm and biopsy arm. Pre- and post-treatment tumor biopsy is optional for participants enrolled in the standard arm, but mandatory for participants enrolled in the biopsy arm....

Clinical Trial Description

Background:

• Pancreatic cancer is the third leading cause of death from cancer in the United States.

• The median overall survival for patients with metastatic disease and excellent performance status receiving the most effective combination chemotherapy regimens remains less than 1 year

• Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer histology, is surrounded by a dense desmoplastic stromal reaction generated by cross-talk between tumor cells and the cancer associated stellate cells (CASC) and fibroblasts (CAF) in the microenvironment.

• This stroma physically inhibits delivery of therapeutic drugs to tumor cells, secretes growth factors and nutrients that promote therapy resistance and cancer cell survival and is also highly immunosuppressive

• Activated CASCs, CAFs and angiogenic endothelial cells which form the abnormal vasculature around tumors, all express high levels of integrin alpha-v-beta3.

• ProAgio is a rationally designed pegylated peptide drug that binds to integrin alpha-v-beta3 at a novel binding site that directly triggers cell apoptosis

• ProAgio induces apoptosis of CASCs and angiogenic endothelial cells in pre-clinical models, inhibiting tumor growth and prolonging animal survival

• Safety of ProAgio in rodent and non-human primate models has been established

• ProAgio has never been tested in humans

Primary Objectives:

To determine the recommended phase 2 dose (RP2D) of ProAgio in participants with previously treated advanced solid tumors for which no curative therapy exists

Eligibility:

• Adults >= 18 years of age

• Histologically confirmed solid tumor malignancy for which no curative therapy exists as confirmed by the NCI Laboratory of Pathology

• For the expansion cohort only: Histologically confirmed diagnosis of pancreatic cancer that is not neuroendocrine

• Participants must have received at least one prior systemic treatment

• Adequate end organ function is required

• Participants in the Biopsy Arm of the expansion cohort must have disease amenable to safe biopsy and willingness to undergo the procedure

Design:

• This is a Phase I study to assess the safety of ProAgio in Participants with advanced solid tumor malignancies including pancreatic cancer

• All participants will receive ProAgio until disease progression, unacceptable toxicity, or withdrawal from study

• For the dose escalation cohort, a modified 3+3 design with accelerated dose escalation in initial cohorts will be used

• For the expansion cohort, all participants will receive ProAgio at the ideal dose identified during the dose escalation

• The expansion cohort has two arms: standard arm and biopsy arm. Pre- and post-treatment tumor biopsy is optional for participants enrolled in the standard arm, but mandatory for participants enrolled in the biopsy arm. ;

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms
• Solid Tumors

• NCT number: NCT04937686
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NCI Medical Oncology Referral Office
• Phone: (240) 760-6050
• Email: ncimo_referrals@nih.gov
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 2, 2021
• Completion date: June 30, 2026