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

NCT01921426 | Completed Phase 1

• 1 other identifier: GT-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

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.

Conditions

Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Oropharynx

Keywords

Squamous Cell Carcinoma of the Head and Neck; Oral Cavity; Oropharynx; Radiation; Chemotherapy; Cisplatin; Oral Mucositis; Superoxide Dismutase

Outcome Measures

Primary Outcomes (1)

• Frequency and Severity of Adverse Events Resulting from GC4419

  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.

  14 - 35 days

Secondary Outcomes (3)

• Rate and Extent of Exposure to GC4419 (Pharmacokinetic Profile)

  18 - 49 Days

• Oral Mucositis

  49 Days

• Antitumor Effect

  14 Months

Other Outcomes (1)

• Pharmacodynamic Profile

  49 Days

Study Arms (1)

GC4419

EXPERIMENTAL

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

Interventions

GC4419 DRUG

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.

GC4419

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galera Therapeutics, Inc.: lead

Study Sites (10)

Lakeland Regional Cancer Center

Lakeland, Florida, 33805, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Summa Health System- Cooper Cancer Center

Akron, Ohio, 44304, United States

Location

St. Luke's Cancer Center

Easton, Pennsylvania, 18045, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

Cancer Care Northwest

Spokane, Washington, 99216, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Stomatitis

Interventions

avasopasem manganese

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Jon T. Holmlund, MD

  Galera Therapeutics, Inc.

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2013
• First Posted: August 13, 2013
• Study Start: August 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2016
• Last Updated: September 22, 2016

Record last verified: 2016-09

Locations

US (10)