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. Patients will also be offered optional co-administration of gemcitabine (Gem). The expansion cohort will contain two arms: A) Biopsy Arm (8 participants), and B) Standard Arm (8 participants). Tumor biopsies performed pre- and post- (on Cycle 2 Day 2-3) ProAgio treatment are optional for participants enrolled in the Standard Arm, but mandatory for participants enrolled in the Biopsy Arm.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
ProAgio is administered to study participants by intravenous injections once every 14 days.
ProAgio is administered to study participants by intravenous injections once every 7 days.
ProAgio is administered to study participants by intravenous injections once every 7 days with a drug holiday after every 5 administrations. Optional co-administration of gemcitabine (Gem) during dose expansion beginning with Cycle 2.
National Cancer Institute
Bethesda, Maryland, United States
Determine Recommended Phase 2 Dose (RP2D)
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.
Time frame: 3 Years
Safety and Tolerability of ProAgio
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.
Time frame: 3 Years
Evaluate the Maximum Plasma Concentration of ProAgio
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.
Time frame: 3 Years
Evaluate the area under the curve of ProAgio
Statistical analysis of study data will calculate the area under the plasma concentration curve for each study subject that received ProAgio.
Time frame: 3 Years
Evaluate the Serum half-life of ProAgio
ProAgio Serum half-life will be determined using standard statistical calculations. .
Time frame: 3 Years
Evaluate the volume of distribution of ProAgio
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.
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Time frame: 3 Years
Rate of study drug elimination in research participants
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.
Time frame: 3 Years
Objective Response Rate (ORR)
Make a preliminary assessment of anti-tumor activity by measuring objective response rate (ORR),
Time frame: 3 Years
Disease control rate (DCR).
Make a preliminary assessment of anti-tumor activity by measuring disease control rate at 18 weeks (DCR).
Time frame: At 18 Weeks
Assess serum tumor marker CA19-9 or appropriate tumor specific marker.
Make a preliminary assessment of anti-tumor activity by measuring change in relevant serum tumor marker CA19-9 appropriate tumor specific marker.
Time frame: Day 1 of each treatment cycle and 30 days after the last dose of study therapy.