Neoplasms

All Conditions

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

Pancreatic Cancer

Micronutrients

All Drugs and Chemicals

Manganese

Avasopasem manganese

Trace Elements

Antioxidants

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)

GC4419 90 mg +55 Gy SBRT

Active Protocol Treatment

Completion of Study -Long Term Follow up

Mouth and Tooth Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Stomatitis

Mucositis

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Oral Squamous Cell Carcinoma

Antineoplastic Agents

Anti-Infective Agents

Vasodilator Agents

Respiratory System Agents

Cisplatin

Hydrogen Peroxide

Superoxide Dismutase

Nitric Oxide

Open label, dose escalation study of GC4419 administered in 14 doses, corresponding to the first 14 doses of radiation therapy. Each dose will be given intravenously over 60 minutes. The possible doses which may be tested are: 15mg, 30mg, 50mg, 75mg, 112mg, and 170mg.

GC4419 is a novel, highly stable manganese-containing macrocyclic ligand complex with a molecular weight of 483, whose activity mimics that of naturally occurring superoxide dismutase (SOD) enzymes. It is therefore a prototype of a new class of drugs termed selective SOD mimetics. GC4419 selectively removes superoxide anions without reacting with other reactive oxygen species, including nitric oxide, hydrogen peroxide, and peroxynitrite.

Jon T. Holmlund, MD

Madhavi Venigalla, MD

Weining Zhen, MD

Douglas Adkins, MD

Pardip Pathare, MD

Sanjiv Agarwala, MD

Charles Kunos, MD, PhD

Yuhchyau Chen, MD, PhD

John Buatti, MD

Aftab Mahmood, MD

Larisa Greenberg, MD

Marcelo Bonomi, MD

Christopher M Lee, MD

The purpose of this study is to determine the safety, tolerability, and the highest dose of GC4419 that can be given to patients with squamous cell cancer of the head and neck who are receiving standard radiation therapy and chemotherapy. This study will also evaluate GC4419 for the following:

* Effect on the incidence and severity of radiation induced oral mucositis;
* Effect on the response rate of squamous cell cancer of the head and neck who are receiving radiation therapy and chemotherapy;
* Total concentrations of GC4419 that can be achieved in the blood;
* Changes in proteins and genetics associated with oral mucositis;
* Impact on delayed toxicities of radiation (dry mouth and reduced ability to fully open the mouth);
* Observe changes in genetic and molecular markers of oral mucositis;
* Observe the usage of extra health resources (e.g., unplanned ER visits, feeding tube use, etc.) of study patients;
* Assess the overall quality of life in study patients with oral mucositis.

This is a multi-center, single-agent, open-label clinical trial to be conducted in serial cohorts of patients with squamous cell cancer of the head and neck receiving escalating doses of GC4419 in combination with standard chemoradiation.

The study will follow a standard 3+3 cohort design typical for phase I clinical trials, in which 3 patients are initially entered at a given dose level and observed for dose-limiting toxicity (DLT). For the purposes of managing dose escalation, the DLT observation window will be defined as the first dose of GC4419 through 24 hours following the last dose of GC4419 for an individual patient. If zero of three patients in a dose cohort experience a DLT during the DLT observation window, enrollment to the next higher dose level will begin. If 1 of 3 patients experiences a DLT within the DLT observation window, 3 additional patients will be added to the dose level. If no DLTs are observed in the 3 additional patients, dose escalations will resume with enrollment to the next higher dose level. If ≥2 patients in a cohort experience a DLT within the DLT observation window, that dose will be considered to have exceeded the MTD. The MTD is defined as the highest dose where ≤ 1 of 6 patients experience a DLT during the DLT observation period.

Decisions to expand a dose cohort or proceed to dose escalation will be made after review of the safety data at a dose level by the Sponsor in collaboration with investigators and appropriately qualified consultants, as needed.

Planned dose levels will be 15, 30, 50, 75, 112, 150, 175, 210, and 250 mg/day, with subsequent dose increments of 50 mg/day, as data warrant or until an MTD is determined. These dose levels represent maximum dose escalation increments. At any time, if ongoing review of safety and other data warrant, intermediate dose levels may be studied (with 3-6 patients enrolled per dose level). These intermediate dose levels may be selected below the next planned dose level or between two dose levels previously studied. If an MTD has not been determined after the 250 mg dose level, further dose escalation may be undertaken at increments of 50 mg/day.

Initial dose escalation will proceed on a treatment schedule wherein GC4419 is administered prior to IMRT on each of the first 14 scheduled days of IMRT. Separate dose cohorts will also be studied wherein GC4419 is administered on each of the first 20, 25, 30, or all 35 days of IMRT (four, five, six, or seven weeks of Active Treatment). Daily dosing of GC4419 by this schedule will begin at a dose that has been shown not to exceed the MTD by the original, 14-dose schedule. Further dose levels may be selected following the same planned dose level guidelines (including possible intermediate dose levels) and rules for determining an MTD as for the 14-dose schedule. At a given daily dose level, extension of the dosing period may be undertaken in increments of one week (5 doses, M-F) per cohort, in successive cohorts. For example, dosing for 20 doses (4 weeks) may proceed at a given dose level only if the MTD has not been exceeded for the same daily dose given for 14 doses; or, dosing for 25 doses (5 weeks) may proceed at a given daily dose level only if the MTD has not been exceeded for the same daily dose given for 20 doses (4 weeks); etc. Note again that, for any cohort and treatment duration, the DLT observation period will extend to 24 hours after the last GC4419 dose for an individual patient. Note also that an extension of dosing duration and an escalation of the daily dose in the same step is not permitted.

In addition, a separate dosing cohort may be concurrently enrolled to receive 30 mg/day, M-F, for 35 doses (7 weeks), based on the calculation that the total dose administered to a given patient (1050 mg) will not exceed the total dose received by 3 patients at 75 mg/d x 14 doses (1050 mg), which was previously determined to be safe (i.e., without any patients having experienced a DLT). If this dose and schedule does not exceed the MTD as defined in this protocol, enrollment of additional 7-week dosing cohorts may be undertaken by applying the same total dose approach to future dose levels administered for \<7 weeks without exceeding the MTD.

On the 14-day schedule, missed doses of GC4419 may be made up prior to study day 28. On schedules employing administration of GC4419 for 20 or more doses, M-F, no GC4419 doses will be made up.

On any schedule, additional patients may be studied at dose levels not exceeding the MTD to characterize the safety, pharmacokinetics, and potential efficacy of GC4419 at those dose levels.

At least one recommended Phase 2 dose, by at least one schedule, will be identified for GC4419. More than one dose may be identified for further assessment of exposure/response relationships. Dose(s) recommended for further study will be at or below the MTD, with exposure and preliminary efficacy data suggesting that they may warrant further investigation for safety and efficacy.

Treatment will be administered on an outpatient basis. Supportive care measures including those directed at controlling symptoms resulting from the patient's malignancy are allowed at the discretion of the treating investigator.

Pharmacokinetic samples will be obtained from all patients.

Primary Objectives:

1. To assess the safety and tolerability of GC4419 when administered with standard chemoradiation, by observation of the frequency and severity of adverse events with the study regimen
2. To determine a Maximum Tolerated Dose/Recommended Phase 2 dose and schedule of GC4419 for further study when administered in combination with standard chemoradiation to patients with squamous cell cancers of the mouth and oropharynx

Secondary Objectives:

1. To determine the pharmacokinetic profile of GC4419 when administered in combination with standard chemoradiation
2. To determine the incidence, severity, time to first onset and duration of oral mucositis in patients receiving GC4419 when administered in combination with standard chemoradiation
3. To preliminarily assess the tumor response to standard chemoradiation when administered in conjunction with GC4419

Exploratory Objectives:

1. To determine the pharmacodynamic effects of GC4419
2. To correlate pharmacokinetic and pharmacodynamic effects of GC4419 with the incidence, severity and time to first onset of oral mucositis
3. To evaluate the potential synergistic effect of GC4419 with chemoradiation on tumor response using pharmacokinetic and pharmacodynamic analyses
4. To evaluate the effect of GC4419 on specific late toxicities (xerostomia and trismus) of standard chemoradiation
5. To collect information about health resource utilization
6. To collect information about health-related quality of life (Oral Mucositis Daily Questionnaire)

A Phase 1 Dose Escalation Study of GC4419 in Combination With Chemoradiation for Squamous Cell Cancer of the Head & Neck

A Phase 1 Dose Escalation Study of GC4419 in Combination With Radiation and Chemotherapy for Squamous Cell Cancers of the Head and Neck.

Determine the pharmacodynamic profile of GC4419 in patients with squamous cell carcinoma of the head and neck receiving GC4419 when administered in combination with standard chemoradiation by observing the changes in proteins and genetic markers associated oral mucositis.

GC4419 will be evaluated to determine safety, tolerability, and the maximum tolerated dose of GC4419 that can be administered to patients with squamous cell cancer of the head and neck who are receiving concurrent radiation (50-70 Gy, administered daily x 5 \[M-F\], in 2.0-2.2 Gy fractions) and chemotherapy (cisplatin, 80-100mg/m2, q3 weeks or weekly cisplatin 30-40mg/m2 x 6 weeks). Patients will receive 14 - 35 doses of GC4419 in serially ascending cohorts for dose and duration, which correspond to the first doses of radiation, schedule dependent. Dose limiting toxicity will be evaluated through 24 hours following the last dose of GC4419.

Determine the pharmacokinetic profile, including the extent and rate of exposure (e.g., maximum concentration, total exposure, half life, time to maximum concentration, accumulation, etc.) to GC4419, as well as GC4419 kinetics (e.g., half-life, in patients with squamous cell carcinoma of the head and neck receiving GC4419 when administered in combination with standard chemoradiation.

Determine the incidence, severity, time to first onset and duration of oral mucositis in patients with squamous cell carcinoma of the head and neck receiving GC4419 when administered in combination with standard chemoradiation.

Preliminarily assess the tumor response to standard chemoradiation when administered in conjunction with GC4419 at approximately 1 year following completion of chemoradiation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pilot Dose Escalation Trial of Stereotactic Body Radiation Therapy (SBRT) in Combination With GC4419 in Pancreatic Cancer	NCT03340974	Pancreatic Canc... Stereotactic Bo...	GC4419 Placebo Stereotactic Ra... Stereotactic Ra...	18 Years -	Galera Therapeutics, Inc.
A Phase 1 Dose Escalation Study of GC4419 in Combination With Chemoradiation for Squamous Cell Cancer of the Head & Neck	NCT01921426	Squamous Cell C... Squamous Cell C...	GC4419	18 Years -	Galera Therapeutics, Inc.

Spots Global Cancer Trial Database for gc4419

Every month we try and update this database with for gc4419 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gc4419

Every month we try and update this database with for gc4419 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gc4419 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.