Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Participants will receive ProAgio in escalating doses.

Participants will receive ProAgio at the RP2D and undergo tumor biopsy.

Participants will receive ProAgio at the RP2D.

ProAgio is administered to study participants by intravenous injections once every 14 days.

ProAgio Dose Levels (DL) 1,2,3

ProAgio is administered to study participants by intravenous injections once every 7 days.

ProAgio Dose Levels (DL) 4,5,6

ProAgio is administered to study participants by intravenous injections once every 7 days with a drug holiday after every 5 administrations.

ProAgio Dose Levels 4a,5a,6a

Damon R Michaels

Zhi-Ren Liu

Eve Koehler, RN, MSN, MPH

Christine Alewine, MD, PhD

The study is a first-in-human, Phase I study to assess the safety of ProAgio in participants with advanced solid tumor malignancies including pancreatic cancer.

Pancreatic cancer is the third leading cause of death from cancer in the United States. The median overall survival for patients with metastatic disease who are receiving the most effective combination of chemotherapy regimens remains less than 1 year.

ProAgio has been evaluated in nonclinical pharmacology, safety pharmacology, pharmacokinetic (PK), and toxicity studies. It has demonstrated efficacy at treating pancreatic cancer and prolonging survival in mice.

ProAgio is being developed for intravenous (IV) administration. All participants will receive ProAgio until disease progression, unacceptable toxicity, or withdrawal from study. Subjects in the dose escalation cohorts who will be administered ProAgio at doses ranging from 3.2 to 36.8 mg/kg.

Following the dose escalation phase, an expansion cohort of patients with advanced nonendocrine pancreatic adenocarcinoma will be administered ProAgio at the maximum tolerated dose (MTD) from the dose escalation phase. The expansion cohort will comprise 16 subjects, divided into two blocks (n=8 each) of patients who agree to have optional pre and post-treatment biopsies, and those who decline the optional biopsies.

This study includes a dose escalation arm, followed by an expansion arm at the ideal dose for participants with non-neuroendocrine pancreatic cancer.

ProAgio in Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies

A Phase I Trial of ProAgio, an Anti- αvβ3 Integrin Cytotoxin, for Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies

Following completion of the dose escalation cohort, all available data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ProAgio will be reviewed by the study team including the Principle Investigator, clinical pharmacology collaborators and the sponsor. A single ideal dose will then be selected for further investigation in the dose escalation cohort. This ideal dose may or may not be the same as the MTD.

Toxicities will be tabulated and reported per dose level according to grade and type of toxicity experienced. This will take place during the dose escalation phase as well as during the expansion phase.

ProAgio concentrations will be measured by a validated ELISA assay modified from the assay used in non-clinical studies. This PK data will be used to mathematically describe the kinetic disposition of ProAgio in humans following the current dosing schedule.

Statistical analysis of study data will calculate the area under the plasma concentration curve for each study subject that received ProAgio.

ProAgio Serum half-life will be determined using standard statistical calculations. .

If there are sufficient participant data available, a population PK analyses will be conducted to identify covariates that may be significantly associated with the inter-individual variability for a particular PK parameter (e.g. clearance of volume of distribution).The NCI CPP may also conduct dose-response and/or exposure-response analyses that will assess PK/PD relationships with relevant biomarkers, clinical response, and adverse event data.

58 study participants will have study drug concentration levels analyzed with regard to drug elimination. Results will be expressed in units of inverse time, i.e. 1/hr or 1/day.

Make a preliminary assessment of anti-tumor activity by measuring objective response rate (ORR),

Make a preliminary assessment of anti-tumor activity by measuring disease control rate at 18 weeks (DCR).

Make a preliminary assessment of anti-tumor activity by measuring change in relevant serum tumor marker CA19-9 appropriate tumor specific marker.

Spots Global Cancer Trial Database for proagio dose levels (dl) 1,2,3