Cetuximab and Recombinant Interleukin-12 in Treating Patients With Squamous Cell Carcinoma of the Head and Neck That is Recurrent, Metastatic, or Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01468896
• Collaborator: (none)
• Enrollment: 23
• Locations: 2
• Arm: 1
• Patients Per Site: 11.5

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of recombinant interleukin-12 when given together with cetuximab and to see how well they work in treating patients with squamous cell carcinoma of the head and neck that has come back, spread to another place in the body, or cannot be removed by surgery. Recombinant interleukin-12 may stimulate the white blood cells to kill tumor cells. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread Giving recombinant interleukin-12 together with cetuximab may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Unresectable Head and Neck Squamous Cell Carcinoma	Biological: Cetuximab; Biological: Edodekin alfa; Other: Laboratory Biomarker Analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To find a safe and tolerable interleukin (IL)-12 (recombinant interleukin-12) dose for use in combination with cetuximab in patients with squamous cell carcinoma of the head and neck. (Phase I) II. To determine the response rate to the combination of IL-12 and cetuximab. (Phase II)

SECONDARY OBJECTIVES:

1. To characterize the immunologic effects of IL-12 when administered in combination with cetuximab.

OUTLINE: This is a phase I, dose-escalation study of recombinant IL-12 followed by a phase II study.

Patients receive cetuximab intravenously (IV) over 1-2 hours on day 1 and recombinant interleukin-12 subcutaneously (SC) on days 2 and 5 beginning in course 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical response or stable disease may continue with therapy until disease progression.

After completion of study treatment, patients are followed up for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of Cetuximab in Combination With Interleukin-12 Administered to Patients With Unresectable Primary or Recurrent Squamous Cell Carcinoma of the Head and Neck
• Actual Study Start Date: Oct 26, 2011
• Actual Primary Completion Date: Sep 29, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (cetuximab and recombinant interleukin-12) Patients receive cetuximab IV over 1-2 hours on day 1 and recombinant interleukin-12 SC on days 2 and 5 beginning in course 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving clinical response or stable disease may continue with therapy until disease progression.

Biological: Cetuximab; Given IV; Other Names: Cetuximab Biosimilar CDP-1 Cetuximab Biosimilar CMAB009 Cetuximab Biosimilar KL 140 Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 ; Biological: Edodekin alfa; Given SC; Other Names: Cytotoxic Lymphocyte Maturation Factor IL-12 Interleukin 12 Interleukin-12 Natural Killer Cell Stimulatory Factor NM-IL-12 Recombinant human interleukin-12 (IL-12) cytokine Ro 24-7472 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Dose-limiting Toxicity Incidents to Determine the Maximum Tolerated Dose of IL-12, Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I) [14 days]

2. Proportion of Patients Who Have Any Response to Treatment (Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors (Phase II) [Up to 6 months]

   The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

Secondary Outcome Measures

1. Induction of Systemic Plasma Levels of Interferon-gamma [Baseline up to day 50]

   Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors.

2. Number of Confirmed Clinical Responses (Phase I) [Up to 6 months]

   Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

3. Overall Survival (Phase II) [From the date of registration to date of death, assessed up to 1 year]

   The Kaplan-Meier method will be used to estimate overall survival distribution.

4. Proportion of Patients Who Are Progression-free (Phase I) [6 months]

   Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.

5. Time to Disease Progression (Phase II) [From date of registration to date of progression, assessed up to 1 year]

   The Kaplan-Meier method will be used to estimate time to progression distributions.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically-proven recurrent and/or metastatic squamous cell carcinoma of the head and neck that is unresectable; patients in the phase II portion of the trial must have measurable disease

• Any number of prior systemic therapies for metastatic/recurrent disease are permitted in both the phase I and II portions of the study; patients need not have received a prior cetuximab-based chemotherapy regimen to be eligible for this trial

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

• Life expectancy of greater than 6 months

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• The effects of IL-12 on the developing human fetus are unknown; for this reason, 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 and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

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

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not be receiving any other investigational agents

• Patients with known brain metastases may be enrolled if this site of disease has been adequately treated, the patient does not require steroids, and the patient has been stable for at least 3 months prior to enrollment

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-12 or other agents used in study

• 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 are excluded from this study because IL-12 is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IL-12, breastfeeding should be discontinued if the mother is treated with IL-12; these potential risks may also apply to other agents used in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
2	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: William E Carson, Ohio State University Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01468896
• Other Study ID Numbers: NCI-2011-03631; NCI-2011-03631; 2011C0019; 11010; CDR0000715306; 8860; 8860; N01CM00070; P30CA016058; U01CA076576; UM1CA186712
• First Posted: Nov 10, 2011
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents, Immunological; Cetuximab; Interleukin-12; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Period Title: Overall Study
STARTED	6	17
COMPLETED	6	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm 1 (Phase 1)	Arm II (Phase II)	Total
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.	Total of all reporting groups
Overall Participants	6	17	23
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56.5	62	61
Sex: Female, Male (Count of Participants)
Female	1 16.7%	0 0%	1 4.3%
Male	5 83.3%	17 100%	22 95.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	6 100%	16 94.1%	22 95.7%
Unknown or Not Reported	0 0%	1 5.9%	1 4.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 5.9%	1 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 5.9%	1 4.3%
White	5 83.3%	14 82.4%	19 82.6%
More than one race	1 16.7%	0 0%	1 4.3%
Unknown or Not Reported	0 0%	1 5.9%	1 4.3%
Region of Enrollment (Count of Participants)
United States	6 100%	17 100%	23 100%

Outcome Measures

1. Primary Outcome

Title	Number of Dose-limiting Toxicity Incidents to Determine the Maximum Tolerated Dose of IL-12, Evaluated Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	6	17
Number [Dose limiting toxicities]	2	0

2. Primary Outcome

Title	Proportion of Patients Who Have Any Response to Treatment (Complete Response or Partial Response), Determined According to Response Evaluation Criteria in Solid Tumors (Phase II)
Description	The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	17
Number [proportion of patients]	0

3. Secondary Outcome

Title	Induction of Systemic Plasma Levels of Interferon-gamma
Description	Explores graphically how changes in this marker differ between those with versus without an objective response to therapy as well as other potential factors.
Time Frame	Baseline up to day 50

Outcome Measure Data

Analysis Population Description

Unable to compare the plasma levels of interferon-gamma between those with versus without an objective response to therapy due to no objective response seen for Phase I or Phase II patients.

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Confirmed Clinical Responses (Phase I)
Description	Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Phase I)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.
Measure Participants	6
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Overall Survival (Phase II)
Description	The Kaplan-Meier method will be used to estimate overall survival distribution.
Time Frame	From the date of registration to date of death, assessed up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	0	17
Median (95% Confidence Interval) [months]	10.6

6. Secondary Outcome

Title	Proportion of Patients Who Are Progression-free (Phase I)
Description	Summarized by simple descriptive summary statistics. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	6	0
Number [proportion of patients]	.17

7. Secondary Outcome

Title	Time to Disease Progression (Phase II)
Description	The Kaplan-Meier method will be used to estimate time to progression distributions.
Time Frame	From date of registration to date of progression, assessed up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 (Phase I)	Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
Measure Participants	0	17
Median (95% Confidence Interval) [months]	4.6

Adverse Events

Adverse Event Reporting Description	Toxicities were graded using the National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Arm/Group Title	Arm 1 (Phase I)		Arm II (Phase II)
Arm/Group Description	Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 (Dose Escalation) on days 2 and 5 of the 2 week cycle, beginning with cycle 2.		Cetuximab 500 mg/m2 i.v. on day 1 of the two week cycle followed by subcutaneous IL-12 at the MTD on days 2 and 5 of the 2 week cycle beginning with cycle 2. No IL-12 is given in the first cycle. IL-12 dosing will begin in cycle 2. The IL-12 dose is 0.3 mcg/kg.
All Cause Mortality
	Arm 1 (Phase I)		Arm II (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 (Phase I)		Arm II (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		9/17 (52.9%)
Cardiac disorders
Atrial fibrillation	0/6 (0%)	0	1/17 (5.9%)	1
Supraventricular tachycardia	0/6 (0%)	0	1/17 (5.9%)	1
Gastrointestinal disorders
Dysphagia	0/6 (0%)	0	1/17 (5.9%)	1
General disorders
General Disorders and administration site conditions	1/6 (16.7%)	1	0/17 (0%)	0
Infections and infestations
Lung infection	0/6 (0%)	0	1/17 (5.9%)	1
Injury, poisoning and procedural complications
Arterial Injury	1/6 (16.7%)	1	0/17 (0%)	0
Investigations
Alkaline phosphatase increased	1/6 (16.7%)	1	0/17 (0%)	0
Lymphocyte count decreased	1/6 (16.7%)	1	0/17 (0%)	0
Metabolism and nutrition disorders
Hyponatremia	1/6 (16.7%)	1	0/17 (0%)	0
Dehydration	0/6 (0%)	0	1/17 (5.9%)	1
Hypercalcemia	0/6 (0%)	0	1/17 (5.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm benign, malignant and unspecified	0/6 (0%)	0	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	0/6 (0%)	0	1/17 (5.9%)	1
Pleuritic pain	0/6 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Arm 1 (Phase I)		Arm II (Phase II)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		17/17 (100%)
Blood and lymphatic system disorders
Anemia	2/6 (33.3%)	2	6/17 (35.3%)	8
Cardiac disorders
Sinus bradycardia	1/6 (16.7%)	1	1/17 (5.9%)	1
Sinus tachycardia	0/6 (0%)	0	1/17 (5.9%)	1
Ear and labyrinth disorders
Ear pain	0/6 (0%)	0	1/17 (5.9%)	1
Hearing impaired	0/6 (0%)	0	1/17 (5.9%)	1
Tinnitus	1/6 (16.7%)	1	0/17 (0%)	0
Endocrine disorders
Hyperthyroidism	0/6 (0%)	0	1/17 (5.9%)	1
Eye disorders
Conjunctivitis	0/6 (0%)	0	1/17 (5.9%)	1
Dry eye	1/6 (16.7%)	1	0/17 (0%)	0
Eye pain	1/6 (16.7%)	1	0/17 (0%)	0
Gastrointestinal disorders
Nausea	6/6 (100%)	9	2/17 (11.8%)	2
Constipation	0/6 (0%)	0	3/17 (17.6%)	3
Diarrhea	0/6 (0%)	0	3/17 (17.6%)	3
Gastroesophageal reflux disease	1/6 (16.7%)	1	2/17 (11.8%)	2
Dry mouth	0/6 (0%)	0	2/17 (11.8%)	2
Dysphagia	0/6 (0%)	0	2/17 (11.8%)	3
Abdominal Pain	0/6 (0%)	0	1/17 (5.9%)	1
Flatuelence	0/6 (0%)	0	1/17 (5.9%)	1
Gastrointestinal Disorder-other	0/6 (0%)	0	1/17 (5.9%)	1
Mucositis oral	1/6 (16.7%)	1	0/17 (0%)	0
Stomach Pain	0/6 (0%)	0	1/17 (5.9%)	1
Vomiting	0/6 (0%)	0	1/17 (5.9%)	4
General disorders
Fatigue	4/6 (66.7%)	4	8/17 (47.1%)	13
Chills	0/6 (0%)	0	5/17 (29.4%)	5
Fever	1/6 (16.7%)	1	4/17 (23.5%)	8
Edema Face	0/6 (0%)	0	2/17 (11.8%)	2
Edema Limbs	1/6 (16.7%)	1	1/17 (5.9%)	1
Flu Like Symptoms	0/6 (0%)	0	2/17 (11.8%)	2
Malaise	0/6 (0%)	0	2/17 (11.8%)	2
General disorders and administration site conditions-other	0/6 (0%)	0	1/17 (5.9%)	1
Pain	0/6 (0%)	0	1/17 (5.9%)	1
Infections and infestations
Paronychia	1/6 (16.7%)	1	2/17 (11.8%)	2
Skin Infection	0/6 (0%)	0	2/17 (11.8%)	2
Esophageal infection	0/6 (0%)	0	1/17 (5.9%)	1
Lung infection	0/6 (0%)	0	1/17 (5.9%)	1
Injury, poisoning and procedural complications
Arterial injury	1/6 (16.7%)	1	0/17 (0%)	0
Intestinal stoma site bleeding	1/6 (16.7%)	1	0/17 (0%)	0
Investigations
Lymphocyte count decreased	6/6 (100%)	10	6/17 (35.3%)	18
Alanine aminotransferase increased	4/6 (66.7%)	6	4/17 (23.5%)	4
Aspartate aminotransferase increased	3/6 (50%)	5	5/17 (29.4%)	11
Alkaline phosphatase increased	2/6 (33.3%)	3	3/17 (17.6%)	9
White blood cell decreased	1/6 (16.7%)	1	4/17 (23.5%)	18
Weight loss	0/6 (0%)	0	4/17 (23.5%)	8
Weight gain	0/6 (0%)	0	2/17 (11.8%)	10
Neutrophil count decreased	0/6 (0%)	0	1/17 (5.9%)	4
Platelet count decreased	0/6 (0%)	0	1/17 (5.9%)	1
Metabolism and nutrition disorders
Hyperglycemia	2/6 (33.3%)	3	6/17 (35.3%)	28
Hyponatremia	2/6 (33.3%)	3	5/17 (29.4%)	15
Hypomagnesemia	1/6 (16.7%)	4	5/17 (29.4%)	17
Anorexia	2/6 (33.3%)	2	3/17 (17.6%)	3
Hypoalbuminemia	3/6 (50%)	3	2/17 (11.8%)	3
Hypophosphatemia	2/6 (33.3%)	4	2/17 (11.8%)	3
Dehydration	1/6 (16.7%)	1	2/17 (11.8%)	4
Hypocalcemia	2/6 (33.3%)	2	1/17 (5.9%)	2
Hypokalemia	0/6 (0%)	0	3/17 (17.6%)	5
Hyperkalemia	0/6 (0%)	0	2/17 (11.8%)	3
Hypoglycemia	1/6 (16.7%)	2	0/17 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/6 (0%)	0	1/17 (5.9%)	2
Generalized muscle weakness	0/6 (0%)	0	1/17 (5.9%)	1
Musculoskeletal and connective disorder-other	0/6 (0%)	0	1/17 (5.9%)	1
Myalgia	0/6 (0%)	0	1/17 (5.9%)	1
Osteonecrosis of jaw	0/6 (0%)	0	1/17 (5.9%)	1
Trismus	0/6 (0%)	0	1/17 (5.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified	0/6 (0%)	0	10/17 (58.8%)	10
Nervous system disorders
Headache	2/6 (33.3%)	2	5/17 (29.4%)	6
Dizziness	1/6 (16.7%)	1	3/17 (17.6%)	3
Facial muscle weakness	0/6 (0%)	0	1/17 (5.9%)	1
Facial nerve disorder	1/6 (16.7%)	1	0/17 (0%)	0
Paresthesia	1/6 (16.7%)	1	0/17 (0%)	0
Psychiatric disorders
Depression	2/6 (33.3%)	2	1/17 (5.9%)	1
Insomnia	1/6 (16.7%)	1	1/17 (5.9%)	1
Renal and urinary disorders
Renal and urinary disorders-other	0/6 (0%)	0	1/17 (5.9%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/6 (0%)	0	4/17 (23.5%)	4
Cough	0/6 (0%)	0	3/17 (17.6%)	4
Dyspnea	1/6 (16.7%)	1	1/17 (5.9%)	1
Laryngeal hemorrhage	2/6 (33.3%)	2	0/17 (0%)	0
Aspiration	0/6 (0%)	0	1/17 (5.9%)	1
Hiccups	1/6 (16.7%)	1	0/17 (0%)	0
Laryngeal inflammation	0/6 (0%)	0	1/17 (5.9%)	2
Pleuritic pain	0/6 (0%)	0	1/17 (5.9%)	1
Pneumonthorax	1/6 (16.7%)	1	0/17 (0%)	0
Respiratory, thoracic and mediastinal	0/6 (0%)	0	1/17 (5.9%)	2
Sore throat	0/6 (0%)	0	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Rash acneiform	3/6 (50%)	7	6/17 (35.3%)	7
Skin and subcutaneous tissue disorder	0/6 (0%)	0	5/17 (29.4%)	5
Dry skin	2/6 (33.3%)	2	2/17 (11.8%)	3
Rash maculo-papular	1/6 (16.7%)	1	9/17 (52.9%)	17
Vascular disorders
Hypertension	1/6 (16.7%)	1	6/17 (35.3%)	21
Hypotension	1/6 (16.7%)	1	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.