Neoplasms

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Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

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Micronutrients

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Manganese

Avasopasem manganese

Trace Elements

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Protective Agents

90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

GC4419

Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

Placebo

Dose-finding will be done using the sequentially adaptive phase I-II Late onset Efficacy-Toxicity (LO-ET) trade-off-based design.

Stereotactic Radiation Therapy (SBRT) 50 Gy

Stereotactic Radiation Therapy (SBRT) 55 Gy

Gene Kennedy, MD

The purpose of the phase I/II clinical study is to determine the best dose of fractionated stereotactic radiation therapy (SBRT) given either with Avasopasem manganese (GC4419) or placebo to patients who have been diagnosed with locally advanced pancreatic cancer.

This is a parallel arm adaptive design phase I-II dose-finding study to determine the optimal dose of fractionated stereotactic radiation therapy (SBRT), given either with the radiomodulating agent Avasopasem manganese (GC4419) or placebo for treatment of locally advanced pancreatic cancer. Dose-finding will be done using the sequentially adaptive phase I-II Late onset Efficacy-Toxicity (LO-ET) trade-off-based design \[1-3\].

A maximum of 48 patients will be randomized 1:1 to Arm A or Arm B. Patients in Arm A will receive Avasopasem manganese (GC4419) in combination with their assigned SBRT dose, and patients in Arm B will receive Placebo (PBO) with their assigned SBRT dose. The randomization will be restricted so that the sample size within each arm is exactly 24 patients.

GC4419/placebo will be given intravenously in a one hour infusion. SBRT must be initiated as soon as possible upon completion of the GC4419/placebo infusion.

GC4419/placebo will be given beginning on the first day of radiation and continuing daily, concurrent M-F throughout the administration of SBRT

Pilot Dose Escalation Trial of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4419 in Pancreatic Cancer

An Adaptive Phase I/II Dose Escalation Trial of Stereotactic Body Radiation Therapy in Combination With Radiomodulating Agent GC4419 in Locally Advanced Pancreatic Adenocarcinoma

Number of Common Terminology Criteria Adverse Events (CTCAE) that are grade 3 or 4 gastro-intestinal (GI) toxicities or deaths. CTCAE grade 3 or 4 gastro-intestinal toxicities are those adverse events that a subject may experience in their gastro-intestinal system that have been graded by the treating investigator to be severe (Grade 3) or life-threatening (Grade 4).

Per Response Evaluation Criteria In Solid Tumors (RECIST) criteria for target lesions that are assessed by radiographic imaging : Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the longest diameter of the target lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for local progressive disease (LPD); Local Progressive Disease (LPD) is at least a 20% increase in the longest diameter of the target lesion, utilizing the baseline measurement as reference.

M.D. Anderson Cancer Center

Galera Therapeutics, Inc.

Avasopasem (GC4419) + SBRT

GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

GC4419 90 mg +50 Gy

GC4419 90mg +55 Gy

Placebo +SBRT

Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

Placebo +50 Gy

Placebo +55 Gy

Total

Age group (years)

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Judy Schnyder, Sr. Vice President Clinical Operations and Data Management

Deaths within 90 days from last dose of study treatment

Grade 3 or 4 Gastrointestinal Toxicities

SBRT + Avasopasem (GC4419)

GC4419: 90 mg Avasopasem (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT .

GC4419 90 mg + 50 Gy

SBRT + Placebo

Placebo: Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level

GC4419 90 mg +55 Gy

Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)

Placebo + 50 Gy SBRT

Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)

Placebo +55 Gy SBRT

Intent-to-Treat (ITT) population, which consisted of all randomized subjects who received at least 1 dose of GC4419/placebo and/or SBRT. The ITT population excluded randomization failures (ie, randomized subjects who did not receive any GC4419/placebo or SBRT).

CTCAE Grade 3 or 4 Gastro-intestinal (GI) Toxicities or Death Within 90 Days From the Start of Therapy

Stable Disease

Partial Response

Progressive Disease

Not Evaluated/Censored

Intent-to-Treat (ITT) population which consisted of all randomized subjects who received at least 1 dose of avasopasem/placebo and/or SBRT with the most restrictive censoring scenario ( subjects censored at the time of surgery, new anti-cancer therapy, and new malignancy)

Radiographic Stable Disease (SD) or Better Based on RECIST Criteria

90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (50 Gy)

GC4419 90 mg +50 Gy SBRT

90 mg Avasopasem manganese (GC4419) per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT (55 Gy)

Spots Global Cancer Trial Database for avasopasem manganese