Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC (GRECO-1)

• ClinicalTrials.gov Identifier: NCT04476797
• Recruitment Status: Recruiting
• First Posted: July 20, 2020
• Last Update Posted: May 31, 2022
• Sponsor: Galera Therapeutics, Inc.
• Information provided by (Responsible Party): Galera Therapeutics, Inc.

Tracking Information

• First Submitted Date: July 15, 2020
• First Posted Date: July 20, 2020
• Last Update Posted Date: May 31, 2022
• Actual Study Start Date: October 18, 2020
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2022)

• Number of dose-limiting toxicities during treatment and within 30 days post SBRT [ Time Frame: DLT 30 days post SBRT ]
  Phase 1
• Percent of patients with a best RECIST response of CR or PR amongst all responses through Month 6 [ Time Frame: 6 months post SBRT ]
  Phase 2

Original Primary Outcome Measures (submitted: July 15, 2020)

• Number of dose-limiting toxicities during treatment and within 30 days post SBRT [ Time Frame: DLT 30 days post SBRT ]
  Phase 1
• DLCO measured by RTOG scale 3 months after completion of SBRT compared to baseline [ Time Frame: DLCO 90 days post SBRT ]
  Phase 2

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase I/II Study of SBRT and GC4711 for Centrally Located or Large NSCLC
• Official Title: GRECO-1: Phase I/II, Randomized, Placebo-Controlled Study of Stereotactic Body Radiation Therapy (SBRT) and GC4711 for Centrally Located or Large, Node-Negative Non-Small Cell Lung Cancer (NSCLC)

Brief Summary

GTI-4711-101 is a Phase I/II study of the safety of GC4711, its effect on in-field tumor response and its potential to reduce radiation-related pulmonary injury due to SBRT for lymph node negative (T1 to T3N0M0) peripheral or central localized (within 2cm of the proximal bronchial tree) NSCLC.

After an open-label, Phase 1, safety cohort of 5 subjects has been completed, a randomized, placebo-controlled Phase 2 portion of 66 subjects will be conducted.

Detailed Description

Subjects must be referred for SBRT with large peripheral lesions (>1cm-7cm) and/or central localized, node negative, non-metastatic NSCLC, and have an ECOG PS score of 0-3. Feasibility of SBRT is judged by the treating physician.

SBRT is planned for the tumor location as a dose of or 3 fractions of 18-20 Gy (Phase 2 only) or 5 fractions of 10-12 Gy. SBRT fractions will be given within 180 minutes from the end of the GC4711 or placebo infusion.

After completion of Phase I, a Phase II, randomized, placebo-controlled study will be initiated, wherein approximately 66 subjects referred for SBRT with early stage large and/or central localized NSCLC will be randomized in a 1:1 ratio to receive either GC4711 or placebo given intravenously (IV) over 15 minutes before each fraction of SBRT, beginning the day of the first fraction of SBRT and ending the last day of SBRT.

Subjects will be monitored for treatment emergent adverse events for 30 days post SBRT completion. Additionally, subjects will be monitored 90 days post-SBRT for all adverse events to evaluate acute toxicities, and monitored for 1-year post-SBRT completion for specific late toxicities.

In-field tumor response and overall survival will be evaluated through 24 months post SBRT completion.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

After the open label Phase 1 portion, subjects in the Phase2 portion will be randomized in a 1:1 ratio to receive GC4711 or placebo before each fraction of SBRT

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

Phase 2 is a randomized, placebo-controlled study

Primary Purpose: Treatment

Condition

• SBRT
• NSCLC
• Non-metastatic

Intervention

• Drug: GC4711
  15 minute IV Infusion prior to SBRT
• Drug: Placebo
  15 minute IV infusion prior to SBRT

Study Arms

• Experimental: GC4711 + SBRT
  Intervention: Drug: GC4711
• Placebo Comparator: Placebo + SBRT
  Intervention: Drug: Placebo

• Publications *: Squillace S, Salvemini D. Nitroxidative stress in pain and opioid-induced adverse effects: therapeutic opportunities. Pain. 2022 Feb 1;163(2):205-213. doi: 10.1097/j.pain.0000000000002347.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 15, 2020): 71
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2023
• Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female subjects at least 18 years of age.
2. Ability to understand and the willingness to sign a written informed consent.
3. Histological or biopsy proven NSCLC.
4. ECOG performance status of 0-3.
5. Node negative (T1 to T3N0M0), centrally located (within 2cm in all directions around the proximal bronchial tree, including ultra-central tumors, abutting the bronchial tree or trachea) or large (>1-7cm) Non-Small Cell Lung Cancer (NSCLC), judged acceptable for SBRT by the treating Investigator

6. Adequate end-organ function, based on routine clinical and laboratory workup:

   1. ANC >1,000 cells/µl, Platelets ≥ 75,000 cells/µl, Hemoglobin ≥ 7.0 g/dl
   2. Serum creatinine ≤ 2 x ULN or calculated creatinine clearance ≥ 30 ml/min
   3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN
7. Males and females of must agree to use effective contraception starting prior to the first day of treatment and continuing after the last dose of GC4711/Placebo for 30 days (females) and 90 days (males).

Exclusion Criteria:

1. Subjects with confirmed nodal and/or distant disease(including brain), according standard workup by local investigator
2. Subjects with peripheral lesions 1cm or smaller
3. Prior treatment with immunotherapy within 3 months prior to Day 1 dosing.
4. Prior intra-thoracic radiotherapy or surgery with substantial overlap to planned radiation fields as determined by the treating radiation oncologist.
5. Subjects not recovered/controlled from prior treatment-related (chemotherapy or targeted therapy) toxicities judged by treating physician.
6. Uncontrolled malignancy other than lung cancer that requires active treatment or is deemed by the treating physicians to be likely to affect the subject's survival duration.
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GC4711.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
9. Participation in other clinical trials actively testing new anti-cancer treatments, unless previously written approval is provided by the Sponsor.
10. 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.
11. Female subjects who are pregnant or breastfeeding.
12. Any other conditions that, in the Investigator's opinion, might indicate the subject to be unsuitable for the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Megan Holm; 484-615-2036; mholm@galeratx.com

Contact: Jon Holmlund, MD; 610-725-1500

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04476797
• Other Study ID Numbers: GTI-4711-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Galera Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Galera Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Jon Holmlund, MD; Chief Medical Officer

• PRS Account: Galera Therapeutics, Inc.
• Verification Date: May 2022