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

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ClinicalTrials.gov Identifier: NCT03340974
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : February 5, 2020
Sponsor:
Collaborator:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Galera Therapeutics, Inc.

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 GC4419 or placebo to patients who have been diagnosed with locally advanced pancreatic cancer.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Stereotactic Body Radiation Therapy Drug: GC4419 Drug: Placebo Radiation: Stereotactic Radiation Therapy (SBRT) Phase 1 Phase 2

Detailed Description:

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 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 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

Objectives:

Primary:

• To determine the Maximum Tolerated Dose (MTD) of Stereotactic Body Radiation Therapy (SBRT) when given in combination with placebo or GC4419

Secondary:

  • To evaluate Progression-free survival (PFS) at MTD for patients treated with SBRT given in combination with placebo or GC4419
  • To evaluate Overall Response Rate (ORR) including stable disease, partial/ complete response for patients treated with SBRT given in combination with placebo or GC4419
  • To evaluate late (12 month) toxicity of SBRT in combination with placebo or GC4419

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Adaptive Phase I/II Dose Escalation Trial of Stereotactic Body Radiation Therapy in Combination With Radiomodulating Agent GC4419 in Locally Advanced Pancreatic Adenocarcinoma
Actual Study Start Date : February 12, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A: SBRT + GC4419 Drug: GC4419
90 mg GC4419 per day daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level, administered Monday - Friday over one week.

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

Placebo Comparator: Arm B: SBRT + Placebo Drug: Placebo
Placebo daily (60 min IV infusion, prior to SBRT), concurrent with daily fractions of SBRT to assigned dose level, administered Monday - Friday over one week.

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




Primary Outcome Measures :
  1. CTCAE grade 3 or 4 gastro-intestinal (GI) toxicities or deaths [ Time Frame: Within 90 days from the start of therapy "related" after CTCAE ]
    Number of CTCAE grade 3 or 4 gastro-intestinal (GI) toxicities or deaths

  2. Radiographic stable disease (SD) based on RECIST criteria [ Time Frame: Evaluated at day 90 from the start of therapy ]
    Radiographic stable disease (SD) or better based on modified RECIST criteria, compared to baseline imaging of the same type



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Cytologic or biopsy confirmed adenocarcinoma of the pancreatic head, body or tail
  2. 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

  3. Pancreatic tumor size and limited bowel involvement by tumor must be judged acceptable for SBRT at the discretion of the treating investigator
  4. No evidence of distant metastasis either prior to or after induction chemotherapy.
  5. 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
  6. Patient must have metal stent in place if duodenal stent is required. If patient has plastic stent, this must be replaced prior to radiation.
  7. 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.
  8. Age 18 years or older
  9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (0, 1 or 2)
  10. 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
  11. 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

  12. Properly obtained written informed consent

Exclusion Criteria:

  1. Prior radiation therapy to the abdomen that would overlap with treatment field
  2. Prior surgical resection of pancreatic tumor
  3. Receiving any approved or investigational anti-cancer agent other than those provided for in this study
  4. Uncontrolled or active gastric or duodenal ulcer disease within 30 days of enrollment
  5. 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.)
  6. Residual or ongoing ≥ Grade 3 non-hematologic toxicity from chemotherapy
  7. Contraindication to IV contrast
  8. 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.
  9. 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
  10. Second primary malignancy within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
  11. 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)
  12. Female patients who are pregnant or breastfeeding
  13. 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.
  14. 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.
  15. 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.
  16. Medical history that includes any condition, or requires the use of concomitant medications which, in the investigator's judgment, are associated with or create a risk of increased carotid sinus sensitivity, symptomatic bradycardia, or syncopal episodes.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03340974


Contacts
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Contact: Melissa Brookes 610-725-1500 mbrookes@galeratx.com
Contact: Jon Holmlund, MD jholmlund@galeratx.com

Locations
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United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Gretchen MacMillan       Gretchen.macmillan@moffitt.org   
Principal Investigator: Sarah Hoffe, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Patrick Boyle       pjboyle@dfci.harvard.edu   
Principal Investigator: Joseph Mancias, MD         
United States, New Jersey
Atlantic Health System / Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07962
Contact: Leah Zitelli       Leah.Cappadona@atlantichealth.org   
Principal Investigator: Mona Karim, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Tykeytr Dale       tykeytra.dale@duke.edu   
Principal Investigator: Brian Czito, MD         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Samantha Mannala       Samantha.Mannala@UTSouthwestern.edu   
Principal Investigator: Todd Aguilera, MD         
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Geena Matthew       geenag@mdanderson.org   
Principal Investigator: Cullen Taniguchi, MD         
Sponsors and Collaborators
Galera Therapeutics, Inc.
M.D. Anderson Cancer Center
Investigators
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Study Chair: Jon Holmlund, MD Galera Therapeutics, Inc.
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Responsible Party: Galera Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03340974    
Other Study ID Numbers: GTI-4419-101
First Posted: November 14, 2017    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Galera Therapeutics, Inc.:
Super Oxide Dismutase
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases