A Study of AT-101 in Combination With Docetaxel in Squamous Cell Carcinoma Of The Head and Neck

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01285635
• Collaborator: (none)
• Enrollment: 35
• Locations: 2
• Arms: 3
• Duration (Months): 63
• Patients Per Site: 17.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will examine the effects of an investigational drug called AT-101 in combination with an FDA approved cancer drug called Docetaxel. It is hoped that AT-101 will help the Docetaxel to have a better effect in slowing or stopping cancer cell growth. This study will help the researchers learn what effects, if any, the combination of AT-101 and Docetaxel has on your cancer. For instance, will the combination cause your tumor(s) to shrink or stop growing? The researchers will also learn about the safety of the combination of AT-101 and Docetaxel. For instance, are there any side effects? If so, what kind of side effects does the combination cause? How severe are the side effects, and how often do they occur?

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)	Drug: AT-101; Drug: Docetaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II of AT-101 in Combination With Docetaxel in Patients With Recurrent, Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Docetaxel Alone	Drug: Docetaxel; Docetaxel 75 mg/m2 on Cycle Day 1
Experimental: Pulse Dose AT-101 Arm	Drug: AT-101; Pulse Dose: AT-101 dose of 40 mg b.i.d. on days 1-3 Metronomic Dose: AT-101, 20 mg daily, days 1-14; Drug: Docetaxel; Docetaxel 75 mg/m2 on Cycle Day 1
Experimental: Metronomic AT-101 Arm	Drug: AT-101; Pulse Dose: AT-101 dose of 40 mg b.i.d. on days 1-3 Metronomic Dose: AT-101, 20 mg daily, days 1-14; Drug: Docetaxel; Docetaxel 75 mg/m2 on Cycle Day 1

Outcome Measures

Primary Outcome Measures

1. Number of Patients With a Complete Response (CR) and Partial Response (PR) [12 months]

   The primary objective is to estimate the proportion of patients with a complete response (CR) and partial response(PR) defined by RECIST (Response Evaluation Criteria in Solid Tumors). CR is defined as the disappearance of all target lesions and PR is defined as at least a 20% decrease in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

1. Median Duration of Response For All Groups Combined [3 years]

2. Incidence of Grade 3 and 4 Toxicities by Arm [3 years]

   Measure the grade III/IV toxicities experienced by patients with advanced, locally recurrent, or metastatic SCCHN

3. Median Overall Survival in Months [3 Years]

4. Median Progression Free Survival in Months [3 Years]

   Progression is defined, by RECIST (Response Evaluation Criteria in Solid Tumors), as at least a 20% increase in the sum of the longest diameter of target lesions.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females at least 18 years old.

2. Histologically or cytologically confirmed diagnosis of SCCHN (Squamous Cell Carcinoma of the Head and Neck).

3. Stage IVC (metastatic), or advanced, locally recurrent SCCHN not amenable to surgery or palliative radiotherapy.

4. Presence of measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumors)

1. If the only site of measurable disease for this study is within a prior field of irradiation, then the sum of the longest diameter (SLD) of that lesion must have increased by at least 20% from the prior treatment nadir

1. Received no more than two prior systemic chemotherapeutic regimen for SCHNN in the locally advanced or metastatic setting and have relapsed after or be refractory to therapy

• Systemic therapies given in the adjuvant setting or with chemoradiotherapy are counted only if the patient relapses after 6 months of the last cycle of chemotherapy or the completion of radiation

• Included as systemic chemotherapy regimens (but not limited to) are patients who may have received erlotinib (Tarceva®) or another EGFR inhibitor. Previous treatment with paclitaxel (but not docetaxel) is permitted.

1. ECOG performance status ≤ 1 (Appendix 2)

2. Expected survival of at least 3 months

3. Adequate liver and renal and bone marrow function as indicated by:

• Serum creatinine ≤ 2.0 times the upper limit of normal, AND

• Serum albumin ≥ 3.0 gm/dL, AND

• Total bilirubin ≤ 1.0 times the upper limit of normal, AND

• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN) for the testing laboratory. Note: For patients with alkaline phosphatase ≥ 2.5 x ULN, the AST and ALT must be ≤ 1.5 x ULN

• Hemoglobin ≥ 9 g/dL (may be post-transfusion);

• Platelet count ≥ 100 x103 cells/mm3

• Neutrophil count ≥1500 cells/mm3

1. Negative pregnancy test for females of childbearing potential

2. Willingness to use contraception by a method that is deemed effective by the Investigator by both males and female patients of childbearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least 30 days following the last dose of AT-101

3. Ability to understand and the willingness to sign a written informed consent form; the consent form must be signed by the patient prior to any study-specific procedures

4. Willingness and ability to comply with study procedures and follow-up examination

Exclusion Criteria:

1. Pregnant or nursing women.

2. Prior docetaxel treatment for SCCHN in the metastatic setting.

3. Treatment of SCCHN with chemotherapy within 28 days of the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible.

4. Treatment with monoclonal antibody (e.g., VEGF or EGFR targeting antibody) within 45 days prior to the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible.

5. Treatment of SCCHN with radiotherapy within 14 days of the first dose of study treatment. Prior radiotherapy is permissible only if the lesions used for determination of disease activity (i.e., target lesions) were not previously irradiated, or have increased in size since the completion of radiotherapy, and the patient has fully recovered from any toxicity of the radiotherapy.

6. Treatment of SCCHN with erlotinib within 14 days of the first dose of study treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1. Patients whose disease responded to the most recently administered prior regimen must have documented progression of disease subsequent to that regimen, to be eligible.

7. Any concurrent therapy intended to treat SCCHN.

8. Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification

9. Symptomatic hypercalcemia or hypercalcemia that is > Grade 2.

10. Participation in any investigational drug study within 28 days prior to study treatment. (Patient must have recovered from all acute effects of previously administered investigational agents).

11. Active secondary malignancy or history of other malignancy within the last five years (patients who have been disease-free for five years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible).

12. Active symptomatic fungal, bacterial and/or viral infection including active HIV. Note: protocol does not require screening for viruses; however, patients with known active infections are excluded.

13. Patients who are contraindicated for treatment with docetaxel.

14. Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, inflammatory bowel disease, partial or complete small bowel obstruction.

15. Uncontrolled CNS (Central Nervous System) metastases. Patients with known, previously treated CNS metastases are eligible if they are neurologically stable, as per the investigating physician's clinical assessment, and do not require steroids at the time of study entry.

16. Prior use of gossypol or AT-101, or known hypersensitivity to gossypol or AT-101.

17. 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.

18. Any patient being treated for acute deep vein thrombosis or patients with a history of recurrent deep vein thrombosis independent of treatment with anticoagulation.

19. Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
2	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Francis Worden, MD, University of Michigan Rogel Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT01285635
• Other Study ID Numbers: UMCC 2010.031; HUM00040432
• First Posted: Jan 28, 2011
• Last Update Posted: Mar 31, 2016
• Last Verified: Mar 1, 2016

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Docetaxel

Study Results

Participant Flow

Pre-assignment Detail	Patients will receive arm specific therapy for the first two cycles, then all patients will be switched into the metronomic AT-101 arm for up to 10 cycles.

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Period Title: First Intervention (2 Weeks)
STARTED	13	11	11
COMPLETED	13	11	11
NOT COMPLETED	0	0	0
Period Title: First Intervention (2 Weeks)
STARTED	13	11	11
COMPLETED	13	11	11
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm	Total
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	Total of all reporting groups
Overall Participants	13	11	11	35
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56	56	59	56
Sex: Female, Male (Count of Participants)
Female	2 15.4%	2 18.2%	2 18.2%	6 17.1%
Male	11 84.6%	9 81.8%	9 81.8%	29 82.9%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With a Complete Response (CR) and Partial Response (PR)
Description	The primary objective is to estimate the proportion of patients with a complete response (CR) and partial response(PR) defined by RECIST (Response Evaluation Criteria in Solid Tumors). CR is defined as the disappearance of all target lesions and PR is defined as at least a 20% decrease in the sum of the longest diameter of target lesions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Measure Participants	13	11	11
Number of Patients with a CR	0	0	0
Number of Patients with a PR	1	1	2

2. Secondary Outcome

Title	Median Duration of Response For All Groups Combined
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

All patients on study

Arm/Group Title	Docetaxel and AT-101
Arm/Group Description	Patients all receive Docetaxel 75mg/m^2 on Day 1. Patients will receive AT-101 on one of the following arms: Arm A: Docetaxel alone for two weeks, then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles. Arm B: AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles Arm C: AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Measure Participants	35
Median (Full Range) [months]	1.9

3. Secondary Outcome

Title	Incidence of Grade 3 and 4 Toxicities by Arm
Description	Measure the grade III/IV toxicities experienced by patients with advanced, locally recurrent, or metastatic SCCHN
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Measure Participants	13	11	11
Fatigue	2 15.4%	1 9.1%	0 0%
Anorexia	1 7.7%	2 18.2%	1 9.1%
Nausea	1 7.7%	5 45.5%	0 0%
Bowel Obstruction	1 7.7%	0 0%	1 9.1%
Hematologic	14 107.7%	8 72.7%	4 36.4%
Infectious	4 30.8%	0 0%	1 9.1%
Respiratory	1 7.7%	0 0%	3 27.3%
Edema	0 0%	2 18.2%	1 9.1%
Other	1 7.7%	2 18.2%	1 9.1%

4. Secondary Outcome

Title	Median Overall Survival in Months
Time Frame	3 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Measure Participants	13	11	11
Median (95% Confidence Interval) [months]	8.3	4.9	4.9

5. Secondary Outcome

Title	Median Progression Free Survival in Months
Description	Progression is defined, by RECIST (Response Evaluation Criteria in Solid Tumors), as at least a 20% increase in the sum of the longest diameter of target lesions.
Time Frame	3 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel Then Metronomic AT-101	Pulse AT-101 Then Metronomic AT-101	Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.	AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
Measure Participants	13	11	11
Median (95% Confidence Interval) [months]	4.5	2.8	4.2

Adverse Events

Arm/Group Title	Docetaxel Then Metronomic AT-101		Pulse AT-101 Then Metronomic AT-101		Metronomic AT-101 Arm
Arm/Group Description	Docetaxel (75 mg/m2 on Cycle Day 1) for 2 weeks then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.		AT-101 (40 mg b.i.d. on days 1-3) then AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.		AT-101 (20mg daily days 1-14) and Docetaxel (75 mg/m2 on Cycle Day 1) for up to 10 cycles.
All Cause Mortality
	Docetaxel Then Metronomic AT-101		Pulse AT-101 Then Metronomic AT-101		Metronomic AT-101 Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Docetaxel Then Metronomic AT-101		Pulse AT-101 Then Metronomic AT-101		Metronomic AT-101 Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)		7/11 (63.6%)		6/11 (54.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Cardiac disorders
Hypotension	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Jejunal obstruction	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Nausea	1/13 (7.7%)		2/11 (18.2%)		0/11 (0%)
Diarrhea	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Upper gastrointestinal hemorrhage	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Vomiting	0/13 (0%)		2/11 (18.2%)		0/11 (0%)
Dysphagia	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Gastrointestinal disorders - Other	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
General disorders
Fatigue	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Pain	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Death NOS	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Infections and infestations
Periorbital infection	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Infections and infestations - Other	0/13 (0%)		2/11 (18.2%)		0/11 (0%)
Sepsis	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Stoma site infection	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Metabolism and nutrition disorders
Anorexia	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Hyponatremia	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Nervous system disorders
Syncope	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/13 (7.7%)		1/11 (9.1%)		0/11 (0%)
Lung infection	2/13 (15.4%)		3/11 (27.3%)		1/11 (9.1%)
Pharyngeal fistula	1/13 (7.7%)		1/11 (9.1%)		0/11 (0%)
Hypoxia	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Laryngeal stenosis	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Dyspnea	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Pharyngeal hemorrhage	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Vascular disorders
Hematoma	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Docetaxel Then Metronomic AT-101		Pulse AT-101 Then Metronomic AT-101		Metronomic AT-101 Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		11/11 (100%)		9/11 (81.8%)
Blood and lymphatic system disorders
Anemia	8/13 (61.5%)		9/11 (81.8%)		7/11 (63.6%)
Lymphocyte count decreased	5/13 (38.5%)		5/11 (45.5%)		5/11 (45.5%)
Neutrophil count decreased	3/13 (23.1%)		1/11 (9.1%)		0/11 (0%)
Platelet count decreased	2/13 (15.4%)		2/11 (18.2%)		2/11 (18.2%)
White blood cell decreased	3/13 (23.1%)		2/11 (18.2%)		1/11 (9.1%)
Leukocytosis	0/13 (0%)		2/11 (18.2%)		0/11 (0%)
Cardiac disorders
Atrial flutter	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Hypotension	1/13 (7.7%)		1/11 (9.1%)		2/11 (18.2%)
Hypertension	0/13 (0%)		1/11 (9.1%)		1/11 (9.1%)
Pericardial effusion	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Sinus tachycardia	0/13 (0%)		1/11 (9.1%)		1/11 (9.1%)
Supraventricular tachycardia	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Ear and labyrinth disorders
Dizziness	3/13 (23.1%)		0/11 (0%)		0/11 (0%)
Otitis externa	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Tinnitus	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Ear pain	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Otitis media	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Endocrine disorders
Hypothyroidism	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Hyperthyroidism	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Hot flashes	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Hyperhidrosis	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Eye disorders
Blurred vision	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Eye disorders - Other	2/13 (15.4%)		0/11 (0%)		1/11 (9.1%)
Scleral disorder	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Watering eyes	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Eye pain	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Eyelid function disorder	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Gastrointestinal disorders
Constipation	5/13 (38.5%)		4/11 (36.4%)		2/11 (18.2%)
Diarrhea	2/13 (15.4%)		3/11 (27.3%)		4/11 (36.4%)
Dysgeusia	1/13 (7.7%)		2/11 (18.2%)		0/11 (0%)
Dyspepsia	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Dysphagia	3/13 (23.1%)		3/11 (27.3%)		0/11 (0%)
Hemorrhoids	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Laryngeal inflammation	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Mucositis oral	2/13 (15.4%)		2/11 (18.2%)		0/11 (0%)
Nausea	5/13 (38.5%)		6/11 (54.5%)		3/11 (27.3%)
Oral pain	1/13 (7.7%)		2/11 (18.2%)		1/11 (9.1%)
Sore throat	1/13 (7.7%)		1/11 (9.1%)		0/11 (0%)
Vomiting	3/13 (23.1%)		4/11 (36.4%)		0/11 (0%)
Abdominal pain	0/13 (0%)		3/11 (27.3%)		0/11 (0%)
Dry mouth	0/13 (0%)		0/11 (0%)		2/11 (18.2%)
Flatulence	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Gastric fistula	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Gastroesophageal reflux disease	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
General disorders
Edema limbs	2/13 (15.4%)		1/11 (9.1%)		1/11 (9.1%)
Fatigue	8/13 (61.5%)		7/11 (63.6%)		5/11 (45.5%)
Fever	1/13 (7.7%)		2/11 (18.2%)		1/11 (9.1%)
Genital edema	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Localized edema	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Pain	3/13 (23.1%)		2/11 (18.2%)		2/11 (18.2%)
Pain in extremity	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Tremor	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Weight loss	3/13 (23.1%)		3/11 (27.3%)		0/11 (0%)
Chills	0/13 (0%)		2/11 (18.2%)		0/11 (0%)
Edema face	0/13 (0%)		1/11 (9.1%)		1/11 (9.1%)
Facial pain	0/13 (0%)		1/11 (9.1%)		2/11 (18.2%)
Gingival pain	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Malaise	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Sinus pain	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Lethargy	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Infections and infestations
Infections and infestations - Other	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Pharyngitis	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Flu like symptoms	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Mucosal infection	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Salivary gland infection	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Skin infection	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Injury, poisoning and procedural complications
Bruising	1/13 (7.7%)		1/11 (9.1%)		1/11 (9.1%)
Infusion related reaction	0/13 (0%)		1/11 (9.1%)		1/11 (9.1%)
Injection site reaction	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Tracheal hemorrhage	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Tracheostomy site bleeding	0/13 (0%)		1/11 (9.1%)		1/11 (9.1%)
Fall	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Surgical and medical procedures - Other	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Investigations
Alanine aminotransferase increased	2/13 (15.4%)		3/11 (27.3%)		1/11 (9.1%)
Alkaline phosphatase increased	3/13 (23.1%)		2/11 (18.2%)		3/11 (27.3%)
Aspartate aminotransferase increased	4/13 (30.8%)		3/11 (27.3%)		2/11 (18.2%)
Cholesterol high	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Creatinine increased	3/13 (23.1%)		1/11 (9.1%)		0/11 (0%)
INR increased	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Metabolism and nutrition disorders
Anorexia	4/13 (30.8%)		6/11 (54.5%)		3/11 (27.3%)
Dehydration	2/13 (15.4%)		0/11 (0%)		2/11 (18.2%)
Hyperglycemia	5/13 (38.5%)		5/11 (45.5%)		5/11 (45.5%)
Hypernatremia	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Hypoalbuminemia	1/13 (7.7%)		2/11 (18.2%)		2/11 (18.2%)
Hypocalcemia	2/13 (15.4%)		2/11 (18.2%)		0/11 (0%)
Hypokalemia	1/13 (7.7%)		2/11 (18.2%)		1/11 (9.1%)
Hyponatremia	2/13 (15.4%)		3/11 (27.3%)		3/11 (27.3%)
Hypophosphatemia	3/13 (23.1%)		4/11 (36.4%)		3/11 (27.3%)
Hypercalcemia	0/13 (0%)		3/11 (27.3%)		0/11 (0%)
Hypomagnesemia	0/13 (0%)		2/11 (18.2%)		1/11 (9.1%)
Metabolism and nutrition disorders - Other	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Hypoglycemia	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Arthritis	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Back pain	1/13 (7.7%)		1/11 (9.1%)		3/11 (27.3%)
Generalized muscle weakness	2/13 (15.4%)		3/11 (27.3%)		1/11 (9.1%)
Myalgia	3/13 (23.1%)		2/11 (18.2%)		0/11 (0%)
Neck pain	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Trismus	0/13 (0%)		3/11 (27.3%)		1/11 (9.1%)
Non-cardiac chest pain	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Nervous system disorders
Headache	2/13 (15.4%)		2/11 (18.2%)		1/11 (9.1%)
Nervous system disorders - Other	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Paresthesia	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Peripheral motor neuropathy	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Peripheral sensory neuropathy	1/13 (7.7%)		1/11 (9.1%)		1/11 (9.1%)
Stroke	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Transient ischemic attacks	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Psychiatric disorders
Agitation	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Confusion	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Delirium	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Depression	1/13 (7.7%)		1/11 (9.1%)		0/11 (0%)
Insomnia	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Anxiety	0/13 (0%)		0/11 (0%)		2/11 (18.2%)
Cognitive disturbance	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Renal and urinary disorders
Urinary frequency	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Renal and urinary disorders - Other	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Urinary incontinence	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Acute kidney injury	0/13 (0%)		0/11 (0%)		1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Cough	2/13 (15.4%)		5/11 (45.5%)		1/11 (9.1%)
Dyspnea	1/13 (7.7%)		5/11 (45.5%)		2/11 (18.2%)
Epistaxis	2/13 (15.4%)		0/11 (0%)		1/11 (9.1%)
Hoarseness	2/13 (15.4%)		1/11 (9.1%)		1/11 (9.1%)
Hypoxia	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Lung infection	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Postnasal drip	2/13 (15.4%)		0/11 (0%)		0/11 (0%)
Productive cough	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Wheezing	1/13 (7.7%)		1/11 (9.1%)		2/11 (18.2%)
Pleural effusion	0/13 (0%)		2/11 (18.2%)		1/11 (9.1%)
Upper respiratory infection	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Skin and subcutaneous tissue disorders
Alopecia	3/13 (23.1%)		1/11 (9.1%)		1/11 (9.1%)
Dry skin	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Flushing	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Nail discoloration	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Pruritus	2/13 (15.4%)		1/11 (9.1%)		0/11 (0%)
Rash acneiform	2/13 (15.4%)		1/11 (9.1%)		0/11 (0%)
Rash pustular	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Skin and subcutaneous tissue disorders - Other	1/13 (7.7%)		1/11 (9.1%)		0/11 (0%)
Rash maculo-papular	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Vascular disorders
Hematoma	0/13 (0%)		1/11 (9.1%)		0/11 (0%)
Lymph node pain	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Lymphedema	1/13 (7.7%)		0/11 (0%)		1/11 (9.1%)
Vascular disorders - Other	1/13 (7.7%)		0/11 (0%)		0/11 (0%)
Thromboembolic event	0/13 (0%)		1/11 (9.1%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE 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.