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

• Sponsor: Galera Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02508389
• Collaborator: (none)
• Enrollment: 223
• Locations: 64
• Arms: 3
• Duration (Months): 46.6
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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; Radiation: Intensity-Modulated Radiation Therapy; Drug: Cisplatin	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 via an intravenous line (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 Design

• Study Type: Interventional
• Actual Enrollment: 223 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 + Intensity-modulated Radiation Therapy (IMRT) for Locally Advanced Non-Metastatic Squamous Cell Carcinoma (SCC) of the Oral Cavity/Oropharynx
• Study Start Date: Oct 12, 2015
• Actual Primary Completion Date: Sep 18, 2017
• Actual Study Completion Date: Aug 29, 2019

Arms and Interventions

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).; Radiation: Intensity-Modulated Radiation Therapy; Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks; Drug: Cisplatin; Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
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).; Radiation: Intensity-Modulated Radiation Therapy; Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks; Drug: Cisplatin; Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
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).; Radiation: Intensity-Modulated Radiation Therapy; Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks; Drug: Cisplatin; Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor

Outcome Measures

Primary Outcome Measures

1. Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria [From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks]

   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. Number of Participants With Treatment-Emergent Adverse Events [First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.]

   Number of participants with treatment emergent adverse events (TEAE) per arm

2. Number of Participants Who Experience Severe OM [Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks.]

   Number of participants who experience severe OM from the first IMRT fraction through the last IMRT fraction

3. Number of Participants Who Experienced Grade 4 OM From the First IMRT Fraction Through the Last IMRT Fraction [First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks.]

   Number of Participants who experienced Grade 4 OM

4. Number of IMRT Fractions Delivered at Onset of Severe OM [Onset of Severe OM, estimated to be between first dose of IMRT and 7 weeks.]

   Onset of severe OM: number of IMRT fractions delivered at onset of severe OM

5. Number of Participants Who Experienced Grade 4 Oral Mucocitis (OM) From the First IMRT Fraction Through the Last IMRT Fraction [Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.]

   Number of Participants who experienced Grade 4 OM

6. Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths [Up to 1 year following completion of chemoradiation.]

   Effect of treatment assignment on tumor outcomes (locoregional failure, distant metastases, progression-free survival, overall survival) Only 73 subjects in Placebo Arm were analyzed for locoregional failure, distant disease and progression-free survival because 1 subject was determined after enrollment to have a non-head and neck cancer and was therefore excluded from these analyses

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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

1. Human papilloma virus (HPV) status in tumor has been documented using tumor immunohistochemistry for HPV-p16 or other accepted test

2. Serum pregnancy test negative for females of childbearing potential

3. 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

4. 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 head and neck cancer (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 (World Health Organization 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center at Dignity Health St. Joseph's	Phoenix	Arizona	United States	85004
2	University of Arizona	Tucson	Arizona	United States	85724
3	Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
4	University of Arkansas for Medical Sciences- Winthrop P. Rockefeller Cancer Institute	Little Rock	Arkansas	United States	72205
5	VA Long Beach Healthcare System	Long Beach	California	United States	90822
6	USC Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
7	Clinical Trials and Research Associates, Inc.	Montebello	California	United States	90604
8	UC Irvine Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
9	Stanford Cancer Institute	Stanford	California	United States	94305
10	St. Mary's Regional Cancer Center	Grand Junction	Colorado	United States	81501
11	UConn Health School of Dental Medicine	Farmington	Connecticut	United States	06030
12	Pasco Pinellas Cancer Center	Holiday	Florida	United States	34691
13	Lakeland Regional Health Cancer Center	Lakeland	Florida	United States	32504
14	UF Health Cancer Center at Orlando Health	Orlando	Florida	United States	32806
15	Sacred Heart Medical Oncology Group	Pensacola	Florida	United States	32504
16	Northwestern University	Chicago	Illinois	United States	60611
17	University of Indianan, Goshen Center for Cancer Care	Goshen	Indiana	United States	46526
18	Department of Radiation Oncology University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
19	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
20	Ashland-Bellefonte Cancer Center	Ashland	Kentucky	United States	41101
21	University of Kentucky, Albert B. Chandler Medical Center	Lexington	Kentucky	United States	40536
22	University of Louisville Hospital, James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
23	Tulane Cancer Center	New Orleans	Louisiana	United States	70112
24	CHRISTUS Schumpert Cancer Treatment Center	Shreveport	Louisiana	United States	71101
25	Baystate Regional Cancer Program	Springfield	Massachusetts	United States	01199
26	University of Michigan	Ann Arbor	Michigan	United States	48109
27	Henry Ford Allegiance Health	Jackson	Michigan	United States	49201
28	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
29	Ellis Fichel Cancer Center, University of Missouri	Columbia	Missouri	United States	65212
30	Billings Clinic	Billings	Montana	United States	59101
31	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59102
32	Renown Cancer Institute	Reno	Nevada	United States	89502
33	Hunterdon Hematology Oncology, LLC Hunterdon Regional Cancer Center	Flemington	New Jersey	United States	08822
34	Jersey Shore University Medical Center- Hackensack Meridian Health	Neptune	New Jersey	United States	07753
35	Montefiore Medical Center	Bronx	New York	United States	10467
36	East Carolina University, Leo W. Jenkins Cancer Center	Greenville	North Carolina	United States	27834
37	Marion L. Shepard Cancer Center	Washington	North Carolina	United States	27889
38	Wake Forest Health	Winston-Salem	North Carolina	United States	27157
39	Ohio State University, James Cancer Center	Columbus	Ohio	United States	43210
40	Toledo Clinic Cancer Center	Toledo	Ohio	United States	43623
41	Oregon Health and Science University	Portland	Oregon	United States	97239
42	VA Portland Health Care System	Portland	Oregon	United States	97239
43	St. Luke's University Health Network	Easton	Pennsylvania	United States	18045
44	Thomas-Jefferson University Hospital-Bodine Center for Cancer Treatment	Philadelphia	Pennsylvania	United States	19107
45	Allegheny General Hospital, Allegheny Cancer Center	Pittsburgh	Pennsylvania	United States	15212
46	Rhode Island Hospital	Providence	Rhode Island	United States	02903
47	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
48	Charleston Cancer Center	Charleston	South Carolina	United States	29406
49	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
50	Prairie Lakes Health Care System	Watertown	South Dakota	United States	57201
51	Mountain States Health Alliance	Johnson City	Tennessee	United States	36704
52	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
53	Texas Oncology	Plano	Texas	United States	75093
54	Scott and White Memorial Hospital and Clinic	Temple	Texas	United States	76508
55	Hope Cancer Center	Tyler	Texas	United States	75701
56	The University of Vermont Medical Center	Burlington	Vermont	United States	05401
57	Providence Regional Medical Center	Everett	Washington	United States	98201
58	VA Puget Sound Health Care System	Seattle	Washington	United States	98108
59	Cancer Care Northwest	Spokane	Washington	United States	99216
60	West Virginia University	Morgantown	West Virginia	United States	26506
61	Northeast Cancer Centre, Health Sciences North	Sudbury	Ontario	Canada	P3E 5J1
62	Jewish General Hospital	Montreal	Quebec	Canada
63	Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-centre-du-Québec	Trois-Rivières	Quebec	Canada	G8Z 3R9
64	Fundación de Investigación	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• Galera Therapeutics, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Oct 19, 2017
• Statistical Analysis Plan - Oct 19, 2017

More Information

Publications

None provided.

• Responsible Party: Galera Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02508389
• Other Study ID Numbers: GT-201
• First Posted: Jul 24, 2015
• Last Update Posted: Sep 20, 2021
• Last Verified: Aug 1, 2021

• 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; Avasopasem manganese

Study Results

Participant Flow

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Period Title: Overall Study
STARTED	73	76	74
COMPLETED	45	45	42
NOT COMPLETED	28	31	32

Baseline Characteristics

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo	Total
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Total of all reporting groups
Overall Participants	73	76	74	223
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (9.10)	57.6 (10.6)	57.9 (9.61)	57.7 (9.76)
Sex: Female, Male (Count of Participants)
Female	9 12.3%	12 15.8%	10 13.5%	31 13.9%
Male	64 87.7%	64 84.2%	64 86.5%	192 86.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.7%	4 5.3%	2 2.7%	8 3.6%
Not Hispanic or Latino	68 93.2%	72 94.7%	70 94.6%	210 94.2%
Unknown or Not Reported	3 4.1%	0 0%	2 2.7%	5 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 1.3%	1 1.4%	2 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 4.1%	3 3.9%	4 5.4%	10 4.5%
White	69 94.5%	71 93.4%	68 91.9%	208 93.3%
More than one race	0 0%	1 1.3%	0 0%	1 0.4%
Unknown or Not Reported	1 1.4%	0 0%	1 1.4%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Duration (in Days) of Radiation Induced Severe Oral Mucositis (OM) Per World Health Organization (WHO) Criteria
Description	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
Time Frame	From start of Intensity-modulated radiation therapy (IMRT) through 8 weeks follow-up, an average of 15 weeks

Outcome Measure Data

Analysis Population Description

intent to treat population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Median (Full Range) [days]	8	1.5	19

2. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events
Description	Number of participants with treatment emergent adverse events (TEAE) per arm
Time Frame	First dose of IMRT through the completion of IMRT, estimated to be up to 7 weeks.

Outcome Measure Data

Analysis Population Description

Treated Population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	72	72
Number of Subjects with at least one TEAE	73 100%	72 94.7%	72 97.3%
Number of Subjects with at least one serious TEAE	34 46.6%	34 44.7%	28 37.8%

3. Secondary Outcome

Title	Number of Participants Who Experience Severe OM
Description	Number of participants who experience severe OM from the first IMRT fraction through the last IMRT fraction
Time Frame	Minimum of 60 Gy administered to tumor, approximately 30 IMRT fractions, which is estimated to be 6-7 weeks.

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Number [participants]	29 39.7%	28 36.8%	43 58.1%

4. Secondary Outcome

Title	Number of Participants Who Experienced Grade 4 OM From the First IMRT Fraction Through the Last IMRT Fraction
Description	Number of Participants who experienced Grade 4 OM
Time Frame	First dose of IMRT through the completion of IMRT, estimated to be up to 6-7 weeks.

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Number [participants]	44 60.3%	33 43.4%	48 64.9%

5. Secondary Outcome

Title	Number of IMRT Fractions Delivered at Onset of Severe OM
Description	Onset of severe OM: number of IMRT fractions delivered at onset of severe OM
Time Frame	Onset of Severe OM, estimated to be between first dose of IMRT and 7 weeks.

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Median (95% Confidence Interval) [IMRT Fractions]	33	35	28

6. Secondary Outcome

Title	Number of Participants Who Experienced Grade 4 Oral Mucocitis (OM) From the First IMRT Fraction Through the Last IMRT Fraction
Description	Number of Participants who experienced Grade 4 OM
Time Frame	Onset of Grade 4 OM, estimated to be between first dose of IMRT and 7 weeks.

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Number [participants]	15 20.5%	12 15.8%	22 29.7%

7. Secondary Outcome

Title	Number of Participants With Tumor Outcomes Defined as Locoregional Failure, Distant Metastases, Disease Progression and Deaths
Description	Effect of treatment assignment on tumor outcomes (locoregional failure, distant metastases, progression-free survival, overall survival) Only 73 subjects in Placebo Arm were analyzed for locoregional failure, distant disease and progression-free survival because 1 subject was determined after enrollment to have a non-head and neck cancer and was therefore excluded from these analyses
Time Frame	Up to 1 year following completion of chemoradiation.

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Low Dose GC4419: 30mg/Day	High Dose GC4419: 90mg/Day	Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor	Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
Measure Participants	73	76	74
Number With Locoregional Failure	7 9.6%	6 7.9%	5 6.8%
Number With Distant Disease	9 12.3%	6 7.9%	6 8.1%
Number with Progressive Disease	15 20.5%	12 15.8%	11 14.9%
Number of Deaths	11 15.1%	10 13.2%	10 13.5%

Adverse Events

Time Frame	from first dose study drug through 30 days after last dose, approximately 11 weeks
Adverse Event Reporting Description	All-cause mortality was reported for all randomized intent-to-treat subjects (ITT) (inclusive of randomization failures who did not get treated). Adverse Events (AEs)/Serious Adverse Events (SAEs) were analyzed for only subjects who received at least one dose of study drug (treated population)
Arm/Group Title	Low Dose GC4419: 30mg/Day		High Dose GC4419: 90mg/Day		Placebo
Arm/Group Description	30 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor		90 mg GC4419/day prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor		Placebo daily, prior to IMRT 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). Intensity-Modulated Radiation Therapy: Daily fractions of IMRT (2.0-2.2 Gy) to a total of 60-72 Gy over approximately 7 weeks Cisplatin: Administered 80-100 mg/m2 once every three weeks for 3 doses or 30-40 mg/m2 once weekly for 6-7 doses. Substitution of other systemic agents due to related toxicities (i.e., carboplatin) would be evaluated to determine eligibility by the Medical Monitor
All Cause Mortality
	Low Dose GC4419: 30mg/Day		High Dose GC4419: 90mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/73 (1.4%)		1/76 (1.3%)		2/73 (2.7%)
Serious Adverse Events
	Low Dose GC4419: 30mg/Day		High Dose GC4419: 90mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/73 (46.6%)		34/72 (47.2%)		28/72 (38.9%)
Blood and lymphatic system disorders
Febrile neutropenia	5/73 (6.8%)		4/72 (5.6%)		3/72 (4.2%)
Anaemia	1/73 (1.4%)		0/72 (0%)		1/72 (1.4%)
Leukopenia	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Lymphopenia	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Cardiac disorders
Atrial fibrillation	1/73 (1.4%)		1/72 (1.4%)		0/72 (0%)
Atrial flutter	2/73 (2.7%)		0/72 (0%)		0/72 (0%)
Acute coronary syndrome	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Bradycardia	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Gastrointestinal disorders
Vomiting	1/73 (1.4%)		2/72 (2.8%)		6/72 (8.3%)
Nausea	3/73 (4.1%)		2/72 (2.8%)		1/72 (1.4%)
Dysphagia	0/73 (0%)		1/72 (1.4%)		3/72 (4.2%)
Constipation	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Diarrhoea	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Duodenal ulcer	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Haematemesis	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Odynophagia	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Upper gastrointestinal haemorrhage	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Dehydration	1/73 (1.4%)		3/72 (4.2%)		2/72 (2.8%)
Decreased appetite	0/73 (0%)		0/72 (0%)		3/72 (4.2%)
Hyponatraemia	2/73 (2.7%)		1/72 (1.4%)		0/72 (0%)
Malnutrition	1/73 (1.4%)		2/72 (2.8%)		0/72 (0%)
Failure to thrive	2/73 (2.7%)		0/72 (0%)		0/72 (0%)
Hyperglycaemia	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Hypocalcaemia	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
General disorders
Pyrexia	3/73 (4.1%)		2/72 (2.8%)		0/72 (0%)
Asthenia	1/73 (1.4%)		1/72 (1.4%)		0/72 (0%)
Mucosal inflammation	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Pain	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Hepatobiliary disorders
Bile duct obstruction	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Infections and infestations
Lung Infection	1/73 (1.4%)		2/72 (2.8%)		2/72 (2.8%)
Pneumonia	0/73 (0%)		2/72 (2.8%)		3/72 (4.2%)
Sepsis	1/73 (1.4%)		1/72 (1.4%)		2/72 (2.8%)
Clostridium difficile infection	2/73 (2.7%)		0/72 (0%)		0/72 (0%)
Oral herpes	1/73 (1.4%)		0/72 (0%)		1/72 (1.4%)
Urinary tract infection	1/73 (1.4%)		1/72 (1.4%)		0/72 (0%)
Bacteraemia	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Cellulitis	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Cellulitis streptococcal	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Cystitis	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Device related infection	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Infected dermal cyst	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Infection	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Lower respiratory tract infection	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Oesophageal candidiasis	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Pharyngitis	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Subcutaneous abscess	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Injury, poisoning and procedural complications
Infusion related reaction	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Investigations
Weight decreased	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Musculoskeletal and connective tissue disorders
Flank pain	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Nervous system disorders
Syncope	1/73 (1.4%)		0/72 (0%)		2/72 (2.8%)
Cerebrovascular accident	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Encephalopathy	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Generalised tonic-clonic seizure	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Guillain-Barre syndrome	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Seizure	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Psychiatric disorders
Alcohol withdrawal syndrome	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Confusional state	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Renal and urinary disorders
Acute kidney injury	5/73 (6.8%)		4/72 (5.6%)		1/72 (1.4%)
Reproductive system and breast disorders
Testicular torsion	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/73 (2.7%)		0/72 (0%)		0/72 (0%)
Pulmonary embolism	0/73 (0%)		1/72 (1.4%)		1/72 (1.4%)
Acute respiratory failure	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Chronic obstructive pulmonary disease	0/73 (0%)		1/72 (1.4%)		0/72 (0%)
Pneumonia aspiration	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Skin and subcutaneous tissue disorders
Rash	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Swelling face	0/73 (0%)		0/72 (0%)		1/72 (1.4%)
Vascular disorders
Hypotension	2/73 (2.7%)		3/72 (4.2%)		2/72 (2.8%)
Deep vein thrombosis	2/73 (2.7%)		0/72 (0%)		1/72 (1.4%)
Hypertension	1/73 (1.4%)		0/72 (0%)		0/72 (0%)
Other (Not Including Serious) Adverse Events
	Low Dose GC4419: 30mg/Day		High Dose GC4419: 90mg/Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/73 (100%)		72/72 (100%)		72/72 (100%)
Blood and lymphatic system disorders
Lymphopenia	67/73 (91.8%)		63/72 (87.5%)		64/72 (88.9%)
Leukopenia	27/73 (37%)		28/72 (38.9%)		28/72 (38.9%)
Neutropenia	18/73 (24.7%)		17/72 (23.6%)		19/72 (26.4%)
Anaemia	20/73 (27.4%)		17/72 (23.6%)		9/72 (12.5%)
Thrombocytopenia	5/73 (6.8%)		7/72 (9.7%)		10/72 (13.9%)
Febrile neutropenia	5/73 (6.8%)		6/72 (8.3%)		3/72 (4.2%)
Cytopenia	5/73 (6.8%)		1/72 (1.4%)		2/72 (2.8%)
Cardiac disorders
Sinus tachycardia	2/73 (2.7%)		4/72 (5.6%)		0/72 (0%)
Ear and labyrinth disorders
Tinnitus	19/73 (26%)		15/72 (20.8%)		19/72 (26.4%)
Ear pain	5/73 (6.8%)		5/72 (6.9%)		4/72 (5.6%)
Hearing impaired	6/73 (8.2%)		2/72 (2.8%)		4/72 (5.6%)
Eye disorders
Vision blurred	0/73 (0%)		7/72 (9.7%)		2/72 (2.8%)
Gastrointestinal disorders
Nausea	50/73 (68.5%)		59/72 (81.9%)		54/72 (75%)
Constipation	43/73 (58.9%)		46/72 (63.9%)		38/72 (52.8%)
Vomiting	38/73 (52.1%)		35/72 (48.6%)		34/72 (47.2%)
Dysphagia	31/73 (42.5%)		34/72 (47.2%)		31/72 (43.1%)
Diarrhoea	31/73 (42.5%)		22/72 (30.6%)		28/72 (38.9%)
Gastrooesophageal reflux disease	9/73 (12.3%)		12/72 (16.7%)		11/72 (15.3%)
Dyspepsia	13/73 (17.8%)		8/72 (11.1%)		6/72 (8.3%)
Salivary hypersecretion	6/73 (8.2%)		11/72 (15.3%)		3/72 (4.2%)
Odynophagia	6/73 (8.2%)		5/72 (6.9%)		4/72 (5.6%)
Abdominal pain	2/73 (2.7%)		2/72 (2.8%)		4/72 (5.6%)
Glossodynia	3/73 (4.1%)		4/72 (5.6%)		1/72 (1.4%)
Flatulence	0/73 (0%)		5/72 (6.9%)		0/72 (0%)
General disorders
Fatigue	44/73 (60.3%)		47/72 (65.3%)		50/72 (69.4%)
Pyrexia	15/73 (20.5%)		13/72 (18.1%)		15/72 (20.8%)
Chills	10/73 (13.7%)		11/72 (15.3%)		10/72 (13.9%)
Oedema peripheral	5/73 (6.8%)		8/72 (11.1%)		6/72 (8.3%)
Asthenia	3/73 (4.1%)		4/72 (5.6%)		5/72 (6.9%)
Face oedema	3/73 (4.1%)		3/72 (4.2%)		4/72 (5.6%)
Pain	1/73 (1.4%)		4/72 (5.6%)		2/72 (2.8%)
Infections and infestations
Oral candidiasis	33/73 (45.2%)		31/72 (43.1%)		21/72 (29.2%)
Candida infection	13/73 (17.8%)		11/72 (15.3%)		12/72 (16.7%)
Urinary tract infection	4/73 (5.5%)		6/72 (8.3%)		2/72 (2.8%)
Mucosal infection	5/73 (6.8%)		2/72 (2.8%)		3/72 (4.2%)
Stoma site infection	0/73 (0%)		5/72 (6.9%)		3/72 (4.2%)
Pharyngitis	1/73 (1.4%)		4/72 (5.6%)		2/72 (2.8%)
Injury, poisoning and procedural complications
Radiation skin injury	37/73 (50.7%)		38/72 (52.8%)		34/72 (47.2%)
Stoma site pain	8/73 (11%)		1/72 (1.4%)		6/72 (8.3%)
Procedural pain	2/73 (2.7%)		0/72 (0%)		4/72 (5.6%)
Investigations
Weight decreased	29/73 (39.7%)		32/72 (44.4%)		25/72 (34.7%)
Electrocardiogram QT prolonged	6/73 (8.2%)		5/72 (6.9%)		4/72 (5.6%)
Metabolism and nutrition disorders
Dehydration	27/73 (37%)		30/72 (41.7%)		23/72 (31.9%)
Decreased appetite	22/73 (30.1%)		31/72 (43.1%)		23/72 (31.9%)
Hypokalaemia	19/73 (26%)		21/72 (29.2%)		13/72 (18.1%)
Hypomagnesaemia	16/73 (21.9%)		18/72 (25%)		16/72 (22.2%)
Hyponatraemia	11/73 (15.1%)		7/72 (9.7%)		10/72 (13.9%)
Hypocalcaemia	3/73 (4.1%)		5/72 (6.9%)		5/72 (6.9%)
Hypophosphataemia	3/73 (4.1%)		3/72 (4.2%)		6/72 (8.3%)
Hyperglycaemia	3/73 (4.1%)		5/72 (6.9%)		3/72 (4.2%)
Malnutrition	2/73 (2.7%)		5/72 (6.9%)		2/72 (2.8%)
Musculoskeletal and connective tissue disorders
Neck pain	7/73 (9.6%)		9/72 (12.5%)		7/72 (9.7%)
Pain in jaw	2/73 (2.7%)		3/72 (4.2%)		8/72 (11.1%)
Back pain	2/73 (2.7%)		5/72 (6.9%)		2/72 (2.8%)
Nervous system disorders
Dysgeusia	40/73 (54.8%)		31/72 (43.1%)		35/72 (48.6%)
Headache	16/73 (21.9%)		24/72 (33.3%)		17/72 (23.6%)
Dizziness	16/73 (21.9%)		19/72 (26.4%)		9/72 (12.5%)
Paraesthesia	7/73 (9.6%)		12/72 (16.7%)		9/72 (12.5%)
Syncope	4/73 (5.5%)		5/72 (6.9%)		4/72 (5.6%)
Psychiatric disorders
Insomnia	11/73 (15.1%)		11/72 (15.3%)		8/72 (11.1%)
Anxiety	8/73 (11%)		6/72 (8.3%)		7/72 (9.7%)
Depression	1/73 (1.4%)		4/72 (5.6%)		6/72 (8.3%)
Confusional state	0/73 (0%)		4/72 (5.6%)		1/72 (1.4%)
Renal and urinary disorders
Acute kidney injury	10/73 (13.7%)		5/72 (6.9%)		8/72 (11.1%)
Renal disorder	4/73 (5.5%)		5/72 (6.9%)		4/72 (5.6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	46/73 (63%)		44/72 (61.1%)		46/72 (63.9%)
Hiccups	17/73 (23.3%)		19/72 (26.4%)		17/72 (23.6%)
Dysphonia	16/73 (21.9%)		16/72 (22.2%)		18/72 (25%)
Cough	13/73 (17.8%)		8/72 (11.1%)		11/72 (15.3%)
Dyspnoea	8/73 (11%)		9/72 (12.5%)		8/72 (11.1%)
Upper-airway cough syndrome	9/73 (12.3%)		5/72 (6.9%)		7/72 (9.7%)
Increased upper airway secretion	3/73 (4.1%)		5/72 (6.9%)		2/72 (2.8%)
Skin and subcutaneous tissue disorders
Dry skin	5/73 (6.8%)		12/72 (16.7%)		11/72 (15.3%)
Pruritus	7/73 (9.6%)		7/72 (9.7%)		6/72 (8.3%)
Alopecia	5/73 (6.8%)		9/72 (12.5%)		3/72 (4.2%)
Erythema	1/73 (1.4%)		4/72 (5.6%)		5/72 (6.9%)
Rash maculo-papular	3/73 (4.1%)		5/72 (6.9%)		1/72 (1.4%)
Skin exfoliation	3/73 (4.1%)		4/72 (5.6%)		2/72 (2.8%)
Skin hyperpigmentation	4/73 (5.5%)		4/72 (5.6%)		1/72 (1.4%)
Rash	5/73 (6.8%)		0/72 (0%)		3/72 (4.2%)
Vascular disorders
Hypotension	12/73 (16.4%)		17/72 (23.6%)		7/72 (9.7%)
Hypertension	7/73 (9.6%)		12/72 (16.7%)		10/72 (13.9%)
Flushing	8/73 (11%)		2/72 (2.8%)		2/72 (2.8%)
Orthostatic hypotension	4/73 (5.5%)		2/72 (2.8%)		4/72 (5.6%)
Deep vein thrombosis	4/73 (5.5%)		1/72 (1.4%)		3/72 (4.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.