A Study of Chemo +/- Low-dose Radiation as Induction Therapy in SCCHN

• Sponsor: Susanne Arnold (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02126969
• Collaborator: (none)
• Enrollment: 45
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 89.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary hypothesis of this study is that hyper-radiosensitivity (HRS) seen at extremely low doses of radiation can be exploited to enhance the effect of chemotherapy, and that this effect differs from the cellular effect of higher, standard fractions of radiation used in traditional radiation treatment paradigms.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer; Larynx	Radiation: Low dose fractionated radiation - 80cGy with chemotherapy; Drug: Docetaxel and Carboplatin AUC 6	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Docetaxel, Carboplatin With and Without Low Dose Radiation as Induction Therapy in Locally Advanced Head and Neck Cancer
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Mar 1, 2018
• Anticipated Study Completion Date: Mar 5, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy plus Radiation Therapy Low dose fractionated radiation - 80cGy with chemotherapy	Radiation: Low dose fractionated radiation - 80cGy with chemotherapy; Chemotherapy + 80 cGy of RT
Active Comparator: Chemotherapy without Radiation Chemotherapy only	Drug: Docetaxel and Carboplatin AUC 6; Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation

Outcome Measures

Primary Outcome Measures

1. Primary Site Complete Response Rate [Up to 50 days]

   Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment.

Secondary Outcome Measures

1. Overall Response Rate [Up to 50 days]

   To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): > 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression).

2. Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. [Up to 50 days (pre- and post-treatment)]

   Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. Physical; scores range from 7-35; higher scores indicate increased well-being Social/family; scores range from 7-35; higher scores indicate increased well-being Emotional; scores range from 6-30; higher scores indicate increased well-being Functional; scores range from 7-35; higher scores indicate increased well-being Additional Concerns; scores range from 10-50; lower scores indicate increased well-being FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being

3. 3-year Overall Survival [Anticipated completion date July 2022]

   . I

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced head and neck cancer of squamous type stage III, IVA and IV B and select Stage II tumors of the BOT who are appropriate for potentially curative therapy with chemoradiotherapy.

• Measurable disease.

• ECOG performance status of 0, 1 or 2

• No prior chemotherapy for the current locally advanced SCCHN.

• Age ≥18 years.

• Life expectancy of greater than 3 months

• Normal organ and marrow function measured within 14 days of registration as defined below:

• absolute neutrophil count ≥ 1,000/mcL

• platelets ≥ 100,000/mcL

• total bilirubin < institutional upper limit of normal

• AST(SGOT ≤ 2.5 × institutional upper limit of normal

• Alkaline phosphatase ≤ 2.5 × institutional upper limit of normal

• creatinine within normal institutional limits

• OR

o Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of active treatment and for 4 months after completion of chemotherapy and radiation. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of active study treatment, and for 4 months after completion of chemotherapy and radiation (both induction and definitive) administration.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior chemotherapy for SCCHN

• Patients who are receiving any other investigational agents.

• Patients with known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Carboplatin or Docetaxel.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women

• HIV-positive patients on combination antiretroviral therapy

• Other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated previous Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 3 years.

• Patients with nasopharynx or salivary gland primary site

• Patients with distant metastatic disease (M1c)

• Patients with grade II or greater peripheral neuropathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Kentucky, Markey Cancer Center	Lexington	Kentucky	United States	40536

Sponsors and Collaborators

• Susanne Arnold

Investigators

• Principal Investigator: Susanne M Arnold, MD, Lucille P. Markey Cancer Center at University of Kentucky

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2018
• Informed Consent Form - Mar 19, 2018

More Information

Publications

None provided.

• Responsible Party: Susanne Arnold, Principal Investigator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT02126969
• Other Study ID Numbers: MCC-13-HN-24
• First Posted: Apr 30, 2014
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Susanne Arnold, Principal Investigator, University of Kentucky: Cancer; Low dose radiation
• Additional relevant MeSH terms: Head and Neck Neoplasms; Carboplatin; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Chemotherapy Plus Radiation Therapy	Chemotherapy Without Radiation
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Period Title: Overall Study
STARTED	23	22
COMPLETED	22	20
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Chemotherapy Plus Radiation Therapy	Chemotherapy Without Radiation	Total
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation	Total of all reporting groups
Overall Participants	23	22	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (6.7)	55 (8.1)	57 (7.4)
Sex: Female, Male (Count of Participants)
Female	5 21.7%	2 9.1%	7 15.6%
Male	18 78.3%	20 90.9%	38 84.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	23 100%	21 95.5%	44 97.8%
Unknown or Not Reported	0 0%	1 4.5%	1 2.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 4.3%	0 0%	1 2.2%
White	22 95.7%	22 100%	44 97.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	22 100%	45 100%

Outcome Measures

1. Primary Outcome

Title	Primary Site Complete Response Rate
Description	Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment.
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy Plus Radiation Therapy	Chemotherapy Without Radiation
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Measure Participants	22	20
Count of Participants [Participants]	6 26.1%	4 18.2%

2. Secondary Outcome

Title	Overall Response Rate
Description	To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): > 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression).
Time Frame	Up to 50 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy Plus Radiation Therapy	Chemotherapy Without Radiation
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Measure Participants	22	20
Overall Complete Response Rate	1 4.3%	1 4.5%
Overall Partial Response Rate	11 47.8%	12 54.5%
Overall Stable Disease Rate	10 43.5%	7 31.8%
overall Progressive Disease Rate	0 0%	0 0%

3. Secondary Outcome

Title	Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy.
Description	Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. Physical; scores range from 7-35; higher scores indicate increased well-being Social/family; scores range from 7-35; higher scores indicate increased well-being Emotional; scores range from 6-30; higher scores indicate increased well-being Functional; scores range from 7-35; higher scores indicate increased well-being Additional Concerns; scores range from 10-50; lower scores indicate increased well-being FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being
Time Frame	Up to 50 days (pre- and post-treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemotherapy Plus Radiation Therapy	Chemotherapy Without Radiation
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT	Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
Measure Participants	22	20
PHYSICAL WELL-BEING SCORE	-1.46 (5.12)	-1.64 (7.22)
SOCIAL/FAMILY WELL-BEING SCORE	-1.34 (4.55)	-2.34 (3.72)
EMOTIONAL WELL-BEING SCORE	2.05 (3.75)	1.60 (4.31)
FUNCTIONAL WELL-BEING SCORE	-0.48 (6.04)	-1.70 (4.92)
FACT-G TOTAL SCORE	-1.23 (13.52)	-4.08 (12.72)
ADDITIONAL CONCERNS SCORE	5.01 (8.24)	3.63 (7.80)
FACT-H&N TOTAL SCORE	3.79 (18.05)	-0.46 (19.16)
TRIAL OUTCOME INDEX SCORE	3.08 (14.55)	0.29 (15.05)

4. Secondary Outcome

Title	3-year Overall Survival
Description	. I
Time Frame	Anticipated completion date July 2022

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	The first subject on was randomized on 1/30/2015 and last subject was randomized on 2/26/2018. Data was collected for AE reporting during treatment and following treatment to the first interval scans, thus AE collection occurred over approximately a 6 month period from randomization to the end of treatment for each subject.
Arm/Group Title	Chemotherapy Plus Radiation Therapy		Chemotherapy Without Radiation
Arm/Group Description	Low dose fractionated radiation - 80cGy with chemotherapy Low dose fractionated radiation - 80cGy with chemotherapy: Chemotherapy + 80 cGy of RT		Chemotherapy only Docetaxel and Carboplatin AUC 6: Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation
All Cause Mortality
	Chemotherapy Plus Radiation Therapy		Chemotherapy Without Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		1/20 (5%)
Serious Adverse Events
	Chemotherapy Plus Radiation Therapy		Chemotherapy Without Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/22 (54.5%)		6/20 (30%)
Blood and lymphatic system disorders
Febrile neutropenia	5/22 (22.7%)	5	1/20 (5%)	1
Cardiac disorders
Cardiac arrest	0/22 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Abdominal pain	1/22 (4.5%)	1	0/20 (0%)	0
Dysphagia	2/22 (9.1%)	2	1/20 (5%)	1
Esophagitis	2/22 (9.1%)	2	0/20 (0%)	0
Nausea	2/22 (9.1%)	2	1/20 (5%)	1
Vomiting	2/22 (9.1%)	2	0/20 (0%)	0
Infections and infestations
Infections and infestations - Other, specify	1/22 (4.5%)	1	0/20 (0%)	0
Sepsis	1/22 (4.5%)	1	1/20 (5%)	1
Skin infection	0/22 (0%)	0	1/20 (5%)	1
Lung infection	5/22 (22.7%)	6	1/20 (5%)	1
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify	1/22 (4.5%)	1	0/20 (0%)	0
Investigations
Neutrophil count decreased	3/22 (13.6%)	3	1/20 (5%)	1
White blood cell decreased	4/22 (18.2%)	4	0/20 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/22 (4.5%)	1	0/20 (0%)	0
Hypoglycemia	1/22 (4.5%)	1	0/20 (0%)	0
Metabolism and nutrition disorders - Other, specify	1/22 (4.5%)	1	0/20 (0%)	0
Glucose intolerance	1/22 (4.5%)	1	0/20 (0%)	0
Nervous system disorders
Syncope	0/22 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/22 (0%)	0	1/20 (5%)	1
Dyspnea	0/22 (0%)	0	1/20 (5%)	1
Laryngeal edema	0/22 (0%)	0	1/20 (5%)	1
Respiratory failure	0/22 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders - Other, specify	1/22 (4.5%)	1	0/20 (0%)	0
Laryngeal obstruction	0/22 (0%)	0	1/20 (5%)	1
Vascular disorders
Hypotension	1/22 (4.5%)	1	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Chemotherapy Plus Radiation Therapy		Chemotherapy Without Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/22 (100%)		20/20 (100%)
Blood and lymphatic system disorders
Anemia	3/22 (13.6%)	5	7/20 (35%)	9
Febrile neutropenia	2/22 (9.1%)	2	1/20 (5%)	1
Cardiac disorders
Sinus tachycardia	0/22 (0%)	0	1/20 (5%)	1
Left ventricular systolic dysfunction	1/22 (4.5%)	1	0/20 (0%)	0
Ear and labyrinth disorders
Hearing impaired	5/22 (22.7%)	6	2/20 (10%)	3
Tinnitus	5/22 (22.7%)	6	6/20 (30%)	6
Eye disorders
Blurred vision	1/22 (4.5%)	1	0/20 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/22 (13.6%)	4	3/20 (15%)	3
Constipation	11/22 (50%)	11	9/20 (45%)	9
Diarrhea	8/22 (36.4%)	8	4/20 (20%)	7
Dry mouth	0/22 (0%)	0	5/20 (25%)	5
Dyspepsia	3/22 (13.6%)	3	1/20 (5%)	1
Dysphagia	4/22 (18.2%)	5	5/20 (25%)	6
Esophagitis	1/22 (4.5%)	1	1/20 (5%)	1
Mucositis oral	18/22 (81.8%)	53	18/20 (90%)	41
Nausea	16/22 (72.7%)	24	16/20 (80%)	24
Rectal hemorrhage	1/22 (4.5%)	1	0/20 (0%)	0
Vomiting	14/22 (63.6%)	19	9/20 (45%)	11
Oral cavity fistula	1/22 (4.5%)	1	0/20 (0%)	0
Gastroesophageal reflux disease	1/22 (4.5%)	1	0/20 (0%)	0
General disorders
Fatigue	8/22 (36.4%)	10	9/20 (45%)	11
Fever	1/22 (4.5%)	1	2/20 (10%)	2
Injection site reaction	0/22 (0%)	0	1/20 (5%)	1
Pain	2/22 (9.1%)	2	1/20 (5%)	1
Edema limbs	1/22 (4.5%)	1	1/20 (5%)	1
Infusion related reaction	0/22 (0%)	0	1/20 (5%)	1
Non-cardiac chest pain	0/22 (0%)	0	1/20 (5%)	1
Hepatobiliary disorders
Hepatic failure	1/22 (4.5%)	1	0/20 (0%)	0
Immune system disorders
Allergic reaction	1/22 (4.5%)	1	0/20 (0%)	0
Infections and infestations
Conjunctivitis infective	0/22 (0%)	0	1/20 (5%)	1
Otitis media	2/22 (9.1%)	2	0/20 (0%)	0
Salivary gland infection	0/22 (0%)	0	1/20 (5%)	1
Sepsis	1/22 (4.5%)	1	0/20 (0%)	0
Sinusitis	1/22 (4.5%)	1	0/20 (0%)	0
Skin infection	2/22 (9.1%)	2	1/20 (5%)	1
Tracheitis	0/22 (0%)	0	1/20 (5%)	1
Upper respiratory infection	0/22 (0%)	0	2/20 (10%)	2
Urinary tract infection	0/22 (0%)	0	1/20 (5%)	1
Vaginal infection	0/22 (0%)	0	1/20 (5%)	1
Wound infection	0/22 (0%)	0	1/20 (5%)	1
Bronchial infection	3/22 (13.6%)	3	1/20 (5%)	1
Enterocolitis infectious	0/22 (0%)	0	1/20 (5%)	1
Lung infection	2/22 (9.1%)	2	1/20 (5%)	1
Stoma site infection	1/22 (4.5%)	1	0/20 (0%)	0
Device related infection	0/22 (0%)	0	1/20 (5%)	1
Mucosal infection	10/22 (45.5%)	12	6/20 (30%)	8
Papulopustular rash	1/22 (4.5%)	1	0/20 (0%)	0
Injury, poisoning and procedural complications
Fall	0/22 (0%)	0	1/20 (5%)	1
Injury, poisoning and procedural complications - Other, specify	1/22 (4.5%)	3	1/20 (5%)	1
Wound dehiscence	1/22 (4.5%)	1	0/20 (0%)	0
Postoperative hemorrhage	1/22 (4.5%)	1	0/20 (0%)	0
Dermatitis radiation	14/22 (63.6%)	20	12/20 (60%)	19
Tracheal hemorrhage	0/22 (0%)	0	1/20 (5%)	1
Tracheostomy site bleeding	1/22 (4.5%)	1	0/20 (0%)	0
Investigations
Alanine aminotransferase increased	1/22 (4.5%)	2	1/20 (5%)	1
Aspartate aminotransferase increased	0/22 (0%)	0	1/20 (5%)	1
Creatinine increased	1/22 (4.5%)	1	1/20 (5%)	1
Lymphocyte count decreased	3/22 (13.6%)	6	3/20 (15%)	6
Neutrophil count decreased	11/22 (50%)	15	4/20 (20%)	5
Platelet count decreased	2/22 (9.1%)	2	1/20 (5%)	3
Weight loss	1/22 (4.5%)	3	5/20 (25%)	6
White blood cell decreased	9/22 (40.9%)	12	4/20 (20%)	5
Metabolism and nutrition disorders
Anorexia	2/22 (9.1%)	2	3/20 (15%)	4
Dehydration	6/22 (27.3%)	6	6/20 (30%)	6
Hyperglycemia	1/22 (4.5%)	1	4/20 (20%)	4
Hypoalbuminemia	0/22 (0%)	0	1/20 (5%)	1
Hypocalcemia	1/22 (4.5%)	1	0/20 (0%)	0
Hypokalemia	0/22 (0%)	0	3/20 (15%)	3
Hyponatremia	2/22 (9.1%)	3	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/22 (4.5%)	1	3/20 (15%)	4
Chest wall pain	0/22 (0%)	0	1/20 (5%)	1
Myalgia	1/22 (4.5%)	1	1/20 (5%)	1
Pain in extremity	1/22 (4.5%)	1	0/20 (0%)	0
Nervous system disorders
Dizziness	1/22 (4.5%)	1	0/20 (0%)	0
Dysgeusia	1/22 (4.5%)	1	5/20 (25%)	5
Encephalopathy	0/22 (0%)	0	1/20 (5%)	1
Headache	1/22 (4.5%)	1	1/20 (5%)	1
Memory impairment	1/22 (4.5%)	1	0/20 (0%)	0
Peripheral motor neuropathy	1/22 (4.5%)	1	1/20 (5%)	2
Peripheral sensory neuropathy	2/22 (9.1%)	2	2/20 (10%)	2
Syncope	0/22 (0%)	0	2/20 (10%)	2
Psychiatric disorders
Anxiety	1/22 (4.5%)	1	1/20 (5%)	1
Confusion	1/22 (4.5%)	1	0/20 (0%)	0
Depression	1/22 (4.5%)	1	1/20 (5%)	1
Insomnia	1/22 (4.5%)	1	3/20 (15%)	3
Suicidal ideation	1/22 (4.5%)	1	0/20 (0%)	0
Renal and urinary disorders
Hematuria	1/22 (4.5%)	1	0/20 (0%)	0
Renal and urinary disorders - Other, specify	1/22 (4.5%)	1	0/20 (0%)	0
Acute kidney injury	1/22 (4.5%)	1	1/20 (5%)	3
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/22 (0%)	0	1/20 (5%)	1
Aspiration	0/22 (0%)	0	2/20 (10%)	2
Cough	3/22 (13.6%)	3	4/20 (20%)	4
Dyspnea	3/22 (13.6%)	3	0/20 (0%)	0
Hiccups	0/22 (0%)	0	1/20 (5%)	1
Laryngeal edema	0/22 (0%)	0	1/20 (5%)	1
Laryngeal stenosis	0/22 (0%)	0	1/20 (5%)	1
Nasal congestion	1/22 (4.5%)	2	1/20 (5%)	1
Respiratory failure	1/22 (4.5%)	1	0/20 (0%)	0
Sore throat	8/22 (36.4%)	9	5/20 (25%)	5
Laryngeal obstruction	1/22 (4.5%)	1	0/20 (0%)	0
Pharyngeal mucositis	1/22 (4.5%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	4/22 (18.2%)	4	6/20 (30%)	6
Pruritus	1/22 (4.5%)	1	0/20 (0%)	0
Rash acneiform	1/22 (4.5%)	2	0/20 (0%)	0
Rash maculo-papular	0/22 (0%)	0	3/20 (15%)	3
Skin and subcutaneous tissue disorders - Other, specify	3/22 (13.6%)	3	1/20 (5%)	1
Vascular disorders
Hematoma	1/22 (4.5%)	1	1/20 (5%)	1
Hypertension	0/22 (0%)	0	1/20 (5%)	1
Hypotension	1/22 (4.5%)	1	0/20 (0%)	0
Thromboembolic event	3/22 (13.6%)	3	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.