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

NCT03340974 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GTI-4419-101
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Pancreatic Cancer; Stereotactic Body Radiation Therapy

Keywords

Avasopasem manganese

Outcome Measures

Primary Outcomes (2)

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

  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).

  Within 90 days from the start of therapy "related" after CTCAE

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

  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.

  All subjects assessed with at least 12 months of follow up following the administration of SBRT

Study Arms (4)

GC4419 90mg +50 Gy SBRT

EXPERIMENTAL

Avasopasem manganese (GC4419) +SBRT

Drug: GC4419; Radiation: Stereotactic Radiation Therapy (SBRT) 50 Gy

GC4419 90 mg + 55 Gy SBRT

EXPERIMENTAL

Avasopasem manganese (GC4419) +SBRT

Drug: GC4419; Radiation: Stereotactic Radiation Therapy (SBRT) 55 Gy

Placebo + 50 Gy SBRT

PLACEBO COMPARATOR

Placebo +SBRT

Drug: Placebo; Radiation: Stereotactic Radiation Therapy (SBRT) 50 Gy

Placebo + 55 Gy SBRT

PLACEBO COMPARATOR

Placebo + SBRT

Drug: Placebo; Radiation: Stereotactic Radiation Therapy (SBRT) 55 Gy

Interventions

GC4419 DRUG

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

Also known as: Avasopasem manganese

GC4419 90 mg + 55 Gy SBRT; GC4419 90mg +50 Gy SBRT

Placebo DRUG

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

Placebo + 50 Gy SBRT; Placebo + 55 Gy SBRT

Stereotactic Radiation Therapy (SBRT) 50 Gy RADIATION

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

GC4419 90mg +50 Gy SBRT; Placebo + 50 Gy SBRT

Stereotactic Radiation Therapy (SBRT) 55 Gy RADIATION

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

GC4419 90 mg + 55 Gy SBRT; Placebo + 55 Gy SBRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologic or biopsy confirmed adenocarcinoma of the pancreatic head, body or tail
• Disease that is appropriate for SBRT by virtue of being:
• a. Locally advanced and technicallyunresectable, as determined by a pancreaticobiliary surgeon as part of a multidisciplinary review at the investigative site, including multi-phasic CT demonstrating: i.Greater than 180 degree tumor involvement of the superior mesenteric artery ii. Greater than 180 degree tumor involvement of the celiac axis, including major branches of the celiac axis that render it unresectable (e.g. common hepatic artery).
• iii. Tumor involvement of the first branch of the SMA that is not surgically reconstructible iv. Long segment involvement of the superior mesenteric vein/portal vein or hepatic artery that is not surgically reconstructible b. Potentially resectable, but patient is judged not a candidate for surgery, after multidisciplinary review at the investigative site; c. Potentially resectable, but the patients refuses surgery and is considered an acceptable candidate for SBRT after multidisciplinary review at the investigative site; d. "Borderline" resectable, as determined by multidisciplinary review, including absence of distant lymphadenopathy and the primary tumor characterized by one of more of the following: i. A tumor-vessel interface (TVI) with the mesenteric vein (SMV) or portal vein (PV) measuring ≥180° of the circumference of either vein's wall or short-segment occlusion of either vein with a normal vein above or below the obstruction amenable to reconstruction; ii. Any TVI with the common hepatic artery (CHA) with normal artery proximal and distal to the TVI amenable to reconstruction; iii. A TVI with the superior mesenteric artery (SMA) measuring \<180° of the circumference of the vessel wall
• Pancreatic tumor size and limited bowel involvement by tumor must be judged acceptable for SBRT at the discretion of the treating investigator
• No evidence of distant metastasis either prior to or after induction chemotherapy.
• Completion of at least 3 months of standard induction chemotherapy for LAPC, which should consist of either FOLFIRINOX, gemcitabine or nab-paclitaxel or another standard combination of induction chemotherapy agents
• Patient must have metal stent in place if duodenal stent is required. If patient has plastic stent, this must be replaced prior to radiation.
• Ability to understand and follow the breathing instructions involved in the respiratory gating procedure or to tolerate compression sufficient to reduce fiducial motion to \<= 5mm.
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (0, 1 or 2)
• Adequate hematologic function as indicated by i. Absolute neutrophil counts (ANC) ≥ 1,500/mm3 ii. Hemoglobin (Hgb) ≥ 8.0 g/dL iii. Platelet count ≥ 75,000/mm3
• Adequate renal and liver function as indicated by:
• i. Creatinine ≤ 1.5 x upper-normal limit (ULN) ii. Total bilirubin ≤ 1.5 x upper-normal limit (ULN) iii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN iv. Alkaline phosphatase ≤ 2.5 x ULN
• Properly obtained written informed consent

You may not qualify if:

• Prior radiation therapy to the abdomen that would overlap with treatment field
• Prior surgical resection of pancreatic tumor
• Receiving any approved or investigational anti-cancer agent other than those provided for in this study
• Uncontrolled or active gastric or duodenal ulcer disease within 30 days of enrollment
• Visible invasion of tumor into the lumen of the bowel or stomach on endoscopy (Note: Radiological infiltration into bowel is allowed, unless deemed clinically unsafe.)
• Residual or ongoing ≥ Grade 3 non-hematologic toxicity from chemotherapy
• Contraindication to IV contrast
• Concurrent participation in another interventional clinical trial or use of another investigational agent within 30 days of study entry Note: Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment
• Second primary malignancy within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
• Known history of HIV or active hepatitis B/C (patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible)
• Female patients who are pregnant or breastfeeding
• Women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for 30 days after the last dose of GC4419. This includes any woman who has experienced menarche but has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months, or women on hormone replacement therapy with serum FSH levels greater than 35 mIU/mL. A negative urine or serum pregnancy test must be obtained within 14 days prior to the start of study therapy in all women of child-bearing potential.
• Male subjects who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 90 days after the last dose of GC4419 are excluded.
• Requirement for concurrent treatment with nitrates or other drugs that may, in the judgment of the treating investigator, create a risk for a precipitous decrease in blood pressure.

Sponsors & Collaborators

• Galera Therapeutics, Inc.: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (6)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Atlantic Health System / Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Hoffe S, Frakes JM, Aguilera TA, Czito B, Palta M, Brookes M, Schweizer C, Colbert L, Moningi S, Bhutani MS, Pant S, Tzeng CW, Tidwell RS, Thall P, Yuan Y, Moser EC, Holmlund J, Herman J, Taniguchi CM. Randomized, Double-Blinded, Placebo-controlled Multicenter Adaptive Phase 1-2 Trial of GC 4419, a Dismutase Mimetic, in Combination with High Dose Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (PC). Int J Radiat Oncol Biol Phys. 2020 Dec 1;108(5):1399-1400. doi: 10.1016/j.ijrobp.2020.09.022. Epub 2020 Nov 18. No abstract available.

  PMID: 33427657 RESULT

• Taniguchi CM, Frakes JM, Aguilera TA, Palta M, Czito B, Bhutani MS, Colbert LE, Abi Jaoude J, Bernard V, Pant S, Tzeng CD, Kim DW, Malafa M, Costello J, Mathew G, Rebueno N, Koay EJ, Das P, Ludmir EB, Katz MHG, Wolff RA, Beddar S, Sawakuchi GO, Moningi S, Slack Tidwell RS, Yuan Y, Thall PF, Beardsley RA, Holmlund J, Herman JM, Hoffe SE. Stereotactic body radiotherapy with or without selective dismutase mimetic in pancreatic adenocarcinoma: an adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial. Lancet Oncol. 2023 Dec;24(12):1387-1398. doi: 10.1016/S1470-2045(23)00478-3.

  PMID: 38039992 DERIVED

• Sishc BJ, Ding L, Nam TK, Heer CD, Rodman SN, Schoenfeld JD, Fath MA, Saha D, Pulliam CF, Langen B, Beardsley RA, Riley DP, Keene JL, Spitz DR, Story MD. Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide. Sci Transl Med. 2021 May 12;13(593):eabb3768. doi: 10.1126/scitranslmed.abb3768.

  PMID: 33980575 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

avasopasem manganese; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Judy Schnyder, Sr. Vice President Clinical Operations and Data Management
• Organization: Galera Therapeutics

jschnyder@galeratx.com

484-870-9625

Study Officials

• Gene Kennedy, MD

  Galera Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: November 14, 2017
• Study Start: February 12, 2018
• Primary Completion: August 21, 2020
• Study Completion: May 26, 2021
• Last Updated: December 15, 2023
• Results First Posted: December 15, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)