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A Study of the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer

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ClinicalTrials.gov Identifier: NCT02508389
Recruitment Status : Active, not recruiting
First Posted : July 24, 2015
Last Update Posted : February 16, 2018
Sponsor:
Information provided by (Responsible Party):
Galera Therapeutics, Inc.

Brief Summary:
The purpose of the phase 2, GT-201 clinical study is to determine if GC4419 administered prior to intensity-modulated radiation therapy (IMRT) reduces the incidence, duration, and severity of radiation induced oral mucositis in patients who have been diagnosed with locally advanced, non-metastatic squamous cell carcinoma of the head and neck.

Condition or disease Intervention/treatment Phase
Radiation Induced Oral Mucositis Drug: Low Dose GC4419: 30mg/day Drug: High Dose GC4419: 90mg/day Drug: Placebo Phase 2

Detailed Description:

GT-201 is a randomized, double-blind, placebo-controlled, multi-center study conducted in the U.S. to evaluate GC4419 administered IV for the reduction of incidence, duration, and severity of radiation induced oral mucositis in patients receiving cisplatin plus intensity-modulated radiation therapy for post-operative, or definitive treatment of locally advanced, non-metastatic squamous cell carcinoma of the head and neck, limited to the oral cavity or oropharynx. Patients will be randomized equally to 1 of 3 treatment arms:

Arm A: 30 mg GC4419 per day (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Arm B: 90 mg GC4419 per day (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Arm C: Placebo daily (60 min IV infusion to complete within 60 minutes prior to IMRT), concurrent with daily fractions of IMRT (2.0 - 2.2 Gy) to a total of 60 - 72 Gy over approximately 7 weeks, plus cisplatin administered 80 - 100 mg/m2 once every three weeks for 3 doses or 30 - 40 mg/m2 once weekly for 6-7 doses (investigator's choice).

Planned radiation fields in all 3 arms must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) with each site receiving a dose of at least 50 Gy.

All patients will be assessed twice weekly for oral mucositis per WHO grading criteria until the completion of IMRT, and once weekly thereafter (if necessary) for 8 weeks, or until oral mucositis resolves to ≤ Grade 1.

Approximately 200 total to ensure that roughly 60 patients per arm receive study drug and complete requirements for primary endpoint analysis, which is defined as patients receiving a minimum cumulative dose of 60 Gy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Trial of the Effects of GC4419 on Severe Oral Mucositis in Patients Receiving Cisplatin + IMRT for Locally Advanced Non-Metastatic SCC of the Oral Cavity/Oropharynx
Study Start Date : October 12, 2015
Actual Primary Completion Date : September 18, 2017
Estimated Study Completion Date : August 2019

Arm Intervention/treatment
Experimental: Low Dose GC4419: 30mg/day
30 mg GC4419/day prior to IMRT
Drug: Low Dose GC4419: 30mg/day
Low Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).

Experimental: High Dose GC4419: 90mg/day
90 mg GC4419/day prior to IMRT
Drug: High Dose GC4419: 90mg/day
High Dose GC4419 will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).

Placebo Comparator: Placebo
Placebo daily, prior to IMRT
Drug: Placebo
Placebo will be administered by 60 minute IV infusion, within 1 hour prior to daily IMRT fractions, until IMRT is complete (generally M-F for approximately 7 weeks).




Primary Outcome Measures :
  1. Duration of Radiation Induced Severe Oral Mucositis per WHO Criteria, Through a Minimum of 60 Gy IMRT Delivered to the Tumor [ Time Frame: Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks. ]
    Evaluate and compare the duration of severe OM, as assessed from the first determination of ≥ Grade 3 OM to the first instance of non-severe OM (≤ Grade 2), without a subsequent instance of ≥ Grade 3.


Secondary Outcome Measures :
  1. Safety of Low Dose vs. High Dose GC4419, Using the Adverse Event Scale: National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v4.0) [ Time Frame: First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks. ]
    Evaluate and compare the safety of GC4419 of each respective arm.

  2. Incidence of Radiation Induced Severe Oral Mucositis per WHO Criteria, Through a Minimum of 60 Gy IMRT Delivered to the Tumor [ Time Frame: Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks. ]
    Evaluate and compare the effects of GC4419, administered at each of two daily doses vs. placebo, on the cumulative incidence of severe OM, defined as any occurrence of WHO Grade 3-4 OM, from the first IMRT fraction through the delivery of the 30th IMRT fraction (approximately 60 Gy delivered to tumor).

  3. Cumulative Incidence of Severe Oral Mucositis, per WHO Criteria for Entire Course of IMRT [ Time Frame: First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks. ]
    Evaluate and compare the cumulative incidence of severe OM from the first IMRT fraction through the last IMRT fraction.

  4. Time to Onset of Severe Oral Mucositis, per WHO Criteria [ Time Frame: Onset of Severe OM, estimated to be between first dose of IMRT and 7 weeks. ]
    Evaluate and compare the time to onset to severe OM: time (days), median IMRT dose delivered, and number of IMRT fractions delivered at onset of severe OM.

  5. Cumulative Incidence of Grade 4 Oral Mucositis, per WHO Criteria [ Time Frame: Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks. ]
    Evaluate and compare the cumulative incidence of Grade 4 OM from the first IMRT fraction through the last IMRT fraction.

  6. Duration of Severe Oral Mucositis, Per WHO Criteria [ Time Frame: Duration of Severe OM, from first observation until resolution to Grade 2 or Less, estimated to be between first dose of IMRT and 15 weeks. ]
    Evaluate and compare the duration of severe OM as assessed by the number of instances of severe OM of >/= 7 days' duration, defined as time from observation of severe OM to the next subsequent observation of OM >/= Grade 2

  7. GC4419's Effect on Tumor Response within 1 Year of IMRT Completion. [ Time Frame: Up to 1 year following completion of chemoradiation. ]
    Evaluate and compare the effect of treatment assignment on tumor outcomes (locoregional failure, distant metastases, progression-free survival, overall survival).


Other Outcome Measures:
  1. OM Incidence by Cumulative IMRT, Per WHO Criteria [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare OM incidence by cumulative IMRT from the first IMRT fraction through the end of post-IMRT early follow-up; post-IMRT early follow-up will extend for up to eight weeks post the last IMRT fraction administered or until a given patient's OM is WHO Grade 0 or 1.

  2. Cumulative Severe OM Incidence at Cumulative Delivery of 20-29, 30-39, 40-49, or 50-59 Gy of IMRT, Per WHO Criteria [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare cumulative severe OM incidence at cumulative delivery of 20-29, 30-39, 40-49, or 50-59 Gy of IMRT

  3. Areas Under the OM-Severity vs. Time Curves [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare the areas under the OM-severity vs. time curves

  4. Number of Patients with Severe OM, per WHO Criteria [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare the number of patients with severe OM on more than one visit prior to week 6, visit 2

  5. Total Number of Days (Per Patient) of Severe OM, per WHO Criteria [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare the total number of days (per patient) of severe OM though the end of IMRTon more than one visit prior to week 6, visit 2

  6. Characterize Effects of GC4419 on Ulcerative (≥ Grade 2) OM, per WHO Criteria [ Time Frame: First Dose of IMRT through 8 weeks of post IMRT follow-up, or resolution to Grade 1 or less. ]
    Evaluate and compare the effects of GC4419 on the incidence, onset, and duration of ulcerative (≥ Grade 2) OM

  7. Compare Effects of GC4419 on Chemoradiation Treatment Delays [ Time Frame: First dose of chemoradiation to last dose of chemoradiation, estimated to be between day 1 and up to 7 weeks. ]
    Evaluate and compare treatment interruptions of chemoradiation.

  8. Compare the Adverse Event Rates of GC4419 Toxicities of Interest within Each Dosing Group: xerostomia, trismus, fatigue, weight loss, radiation dermatitis, and dysgeusia [ Time Frame: First Dose of IMRT, up to approximately 7 weeks. ]
    Evaluate and compare the effects of GC4419 on other specific toxicities of interest associated with concurrent chemoradiation: xerostomia, trismus, fatigue, weight loss, radiation dermatitis, and dysgeusia (changes in taste).

  9. Compare the Results of Patient Reported Outcomes, Specifically the Oral Mucositis Daily Questionnaire within Each Dosing Group [ Time Frame: First Dose of IMRT, up to approximately 7 weeks. ]
    Evaluate and compare the effects of treatment on patient-reported outcomes as obtained using the Oral Mucositis Daily Questionnaire (OMDQ).

  10. Effect of GC4419 on Narcotic Analgesic Requirements [ Time Frame: First Dose of IMRT through the last dose of IMRT, expected to be between first dose and 7 weeks. ]
    To evaluate and compare the use of narcotic analgesics by patients according to treatment assignment.

  11. Effect of GC4419 on Gastronomy Tube Dependence [ Time Frame: Date of gastronomy tube placement through the date of removal, which is expected to be between and average of 7 days prior to starting IMRT and up to 15 weeks. ]
    Evaluate the requirement for use of gastrostomy tubes.

  12. Compare the Complication Rates of Indwelling Venous Access Devices Among All Dosing Groups [ Time Frame: Date of indwelling venous access devices through the date of removal, which is expected to be an average of up to 7 weeks. ]
    Evaluate and compare the use and complications of indwelling venous access devices.

  13. Effect of GC4419 on Requirement for Unscheduled Hospitalizations [ Time Frame: First dose of chemoradiation through the last dose of chemoradiation, expected to be between day 1 and 7 weeks. ]
    To evaluate and compare the requirement for unscheduled hospitalizations.

  14. Effect of GC4419 on Biologic Markers of Response [ Time Frame: First dose of IMRT through the last dose of IMRT, expected to be between day 1 and 7 weeks. ]
    To assess the effects of treatment assignment on biologic markers of response.



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. Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck, defined as SCC of the oral cavity or oropharynx that will be treated with cisplatin plus concurrent IMRT Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criteria #2 and #3 below are eligible for the trial.
  2. Treatment plan to receive a continuous course of IMRT delivered as single daily fractions of 2.0 to 2.2 Gy with a cumulative radiation dose between 60 Gy and 72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, tongue, soft palate) that are each planned to receive a total of > 50 Gy. Patients who have had prior surgery are eligible, provided they have fully recovered from surgery, and patients who may have surgery in the future are eligible.
  3. Treatment plan to receive standard cisplatin monotherapy administered either every three weeks (80-100 mg/m2 for 3 doses) or weekly (30-40 mg/m2 for 6-7 doses). The decision on which chemotherapy regimen to use in combination with IMRT and GC4419 will be at the discretion of the investigator.
  4. Age 18 years or older
  5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  6. Adequate hematologic function as indicated by:

    • Absolute neutrophil counts (ANC) ≥ 1,500/mm3
    • Hemoglobin (Hgb) ≥ 9.0 g/dL
    • Platelet count ≥ 100,000/mm3
  7. Adequate renal and liver function as indicated by:

    • Serum creatinine acceptable for treatment with cisplatin per institutional guidelines
    • Total bilirubin ≤ 1.5 x upper-normal limit (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x ULN
  8. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test
  9. Serum pregnancy test negative for females of childbearing potential
  10. Males and females must agree to use effective contraception starting prior to the first day of treatment and continuing for 30 days after the last dose of GC4419
  11. Properly obtained written informed consent

Exclusion Criteria:

  1. Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
  2. Metastatic disease (Stage IV C)
  3. Prior radiotherapy to the region of the study cancer or adjacent anatomical sites or more than 25% of total body marrow-bearing area (potentially interfering with chemotolerance)
  4. Prior induction chemotherapy
  5. Receiving any approved or investigational anti-cancer agent other than those provided for in this study
  6. Participation in another clinical trial or use of another investigational agent within 30 days of study entry
  7. Requirement for significantly modified diet (liquids and/or solids) due to compromised oral/pharyngeal function at baseline
  8. Requirement at baseline for parenteral or gastrointestinal tube-delivered nutrition for any reason
  9. Malignant tumors other than HNC within the last 5 years, unless treated definitively and with low risk of recurrence in the judgment of the treating investigator
  10. Active infectious disease excluding oral candidiasis
  11. Presence of oral mucositis (WHO Score ≥ Grade 1) at study entry
  12. 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)
  13. Female patients who are pregnant or breastfeeding
  14. Known allergies or intolerance to cisplatin and similar platinum-containing compounds
  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

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): NCT02508389


  Show 61 Study Locations
Sponsors and Collaborators
Galera Therapeutics, Inc.
Investigators
Study Chair: Jon T Holmlund, MD Chief Medical Officer

Responsible Party: Galera Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02508389     History of Changes
Other Study ID Numbers: GT-201
First Posted: July 24, 2015    Key Record Dates
Last Update Posted: February 16, 2018
Last Verified: February 2018

Keywords provided by Galera Therapeutics, Inc.:
squamous cell carcinoma of the head and neck
oral cavity
oropharynx
intensity-modulated radiation therapy
chemotherapy
oral mucositis
superoxide dismutase
radioprotection

Additional relevant MeSH terms:
Mucositis
Stomatitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases