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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01921426
Recruitment Status : Completed
First Posted : August 13, 2013
Last Update Posted : September 22, 2016
Information provided by (Responsible Party):
Galera Therapeutics, Inc.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Oral Cavity Squamous Cell Carcinoma of the Oropharynx Drug: GC4419 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase 1 Dose Escalation Study of GC4419 in Combination With Radiation and Chemotherapy for Squamous Cell Cancers of the Head and Neck.
Study Start Date : August 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: GC4419
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.
Drug: GC4419
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.

Primary Outcome Measures :
  1. Frequency and Severity of Adverse Events Resulting from GC4419 [ Time Frame: 14 - 35 days ]
    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.

Secondary Outcome Measures :
  1. Rate and Extent of Exposure to GC4419 (Pharmacokinetic Profile) [ Time Frame: 18 - 49 Days ]
    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.

  2. Oral Mucositis [ Time Frame: 49 Days ]
    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.

  3. Antitumor Effect [ Time Frame: 14 Months ]
    Preliminarily assess the tumor response to standard chemoradiation when administered in conjunction with GC4419 at approximately 1 year following completion of chemoradiation.

Other Outcome Measures:
  1. Pharmacodynamic Profile [ Time Frame: 49 Days ]
    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.

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

Inclusion Criteria:

  • Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck (SCCHN), defined as SCC of the oral cavity or oropharynx, that will be treated with standard cisplatin and Intensity-Modulated Radiation Therapy (IMRT)
  • Males or females aged 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate bone marrow, liver and kidney function
  • Negative serum pregnancy test for females of childbearing potential
  • Properly obtained written informed consent

Exclusion Criteria:

  • Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, salivary glands or unknown primary tumor
  • Metastatic disease (Stage IV C)
  • Prior chemotherapy for SCCHN and/or radiotherapy to the region of the study cancer or
  • Receiving any agent classified as an antioxidant
  • History of malignant tumors other than SCCHN within the last 5 years, except non-melanoma skin cancer or curatively excised in situ cervical carcinoma
  • Active infectious disease excluding oral candidiasis
  • Presence of oral mucositis at study entry
  • Chronic immunosuppression
  • Known history of HIV or active hepatitis B/C )
  • Prior history of hearing impairment
  • Use of investigational agent within 30 days of study entry
  • Known allergies or intolerance to cisplatin and similar platinum-containing compounds
  • 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

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 identifier (NCT number): NCT01921426

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United States, Florida
Lakeland Regional Cancer Center
Lakeland, Florida, United States, 33805
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Summa Health System- Cooper Cancer Center
Akron, Ohio, United States, 44304
United States, Pennsylvania
St. Luke's Cancer Center
Easton, Pennsylvania, United States, 18045
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212
United States, Washington
Cancer Care Northwest
Spokane, Washington, United States, 99216
Sponsors and Collaborators
Galera Therapeutics, Inc.
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Study Director: Jon T. Holmlund, MD Galera Therapeutics, Inc.
Principal Investigator: Madhavi Venigalla, MD Lakeland Regional Cancer Center
Principal Investigator: Weining Zhen, MD University of Nebraska
Principal Investigator: Douglas Adkins, MD Washington University School of Medicine
Principal Investigator: Pardip Pathare, MD Norwalk Hospital
Principal Investigator: Sanjiv Agarwala, MD St. Luke's Cancer Center
Principal Investigator: Charles Kunos, MD, PhD Summa Health System- Cooper Cancer Center
Principal Investigator: Yuhchyau Chen, MD, PhD University of Rochester
Principal Investigator: John Buatti, MD University of Iowa
Principal Investigator: Aftab Mahmood, MD Cancer Specialists of South Texas, P.A.
Principal Investigator: Larisa Greenberg, MD West Penn Allegheny Health System
Principal Investigator: Marcelo Bonomi, MD Wake Forest University Health Sciences
Principal Investigator: Christopher M Lee, MD Cancer Care Northwest
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Responsible Party: Galera Therapeutics, Inc. Identifier: NCT01921426    
Other Study ID Numbers: GT-001
First Posted: August 13, 2013    Key Record Dates
Last Update Posted: September 22, 2016
Last Verified: September 2016
Keywords provided by Galera Therapeutics, Inc.:
Squamous Cell Carcinoma of the Head and Neck
Oral Cavity
Oral Mucositis
Superoxide Dismutase
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Avasopasem manganese
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs