Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01225887
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 37
• Locations: 59
• Arm: 1
• Duration (Months): 51
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects and how well nintedanib works in treating patients with endometrial cancer that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma	Drug: Nintedanib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the proportion of patients with persistent or recurrent endometrial cancer, who survive progression-free without going on a subsequent therapy against the disease for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with BIBF 1120 (nintedanib).

2. To determine the nature and degree of toxicity of BIBF 1120 in this cohort of patients.

SECONDARY OBJECTIVES:

1. To estimate the progression-free survival (PFS) and overall survival (OS) of patients with persistent or recurrent endometrial cancer treated with BIBF 1120.

OUTLINE:

Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of BIBF 1120 in the Treatment of Recurrent or Persistent Endometrial Carcinoma
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (nintedanib) Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Nintedanib; Given PO; Other Names: BIBF 1120 BIBF-1120 Intedanib Multitargeted Tyrosine Kinase Inhibitor BIBF 1120 tyrosine kinase inhibitor BIBF 1120 Vargatef

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [Up to 5 years]

   The incidence of adverse events (grade 3 or higher) as assessed by the National Cancer Institute CTCAE version 4.0

2. Objective Tumor Response [For disease that can be evaluated by physical exam,response was assessed prior to each cycle CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.]

   Complete and Partial Tumor Response by RECIST 1.1

3. Progression-free Survival > 6 Months [for disease that can be evaluated by physical exam, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.]

   Whether or not the patient survived progression-free for at least 6 months.

Secondary Outcome Measures

1. Overall Survival [From study entry to death or last contact, up to 5 years]

   The observed length of life from entry into the study to death or the date of last contact.

2. Progression Free Survival [The duration of time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years]

   the period of progression free survival for patients with persistent or recurrent endometrial cancer treated with study drug.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma

• All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG Phase III protocol or Rare Tumor protocol for the same patient population

• Patients must have a GOG performance status of 0, 1, or 2

• Patients must have normal thyroid function; patients with a history of hypothyroidism are eligible, provided it is well controlled on medication

• Recovery from effects of recent surgery, radiotherapy, or chemotherapy

• Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection)

• Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration

• Any other prior therapy directed at the malignant tumor, including chemotherapy and immunologic agents, must be discontinued at least three weeks prior to registration

• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer will be counted as a systemic chemotherapy regimen

• Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease

• Patients must have NOT received any non-cytotoxic (biologic or targeted) agents, as part of their primary treatment or for management of recurrent or persistent disease; non-cytotoxic (biologic or targeted) agents include (but are not limited to) monoclonal antibodies, cytokines, and small-molecule inhibitors of signal transduction; prior hormonal therapy is allowed; there is no limit on the number of prior hormonal therapies allowed

• Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl

• Platelets greater than or equal to 100,000/mcl

• Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)

• Urine protein creatinine (UPC) ratio must be < 1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is recommended

• Bilirubin must be less than 1.5 X ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than 3 X ULN

• Alkaline phosphatase must be less than 2.5 X ULN

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal

• Electrocardiogram (EKG) must have corrected QT interval (QTc) < 450 msec without evidence of serious ventricular arrhythmia (ventricular tachycardia lasting more than 3 beats or ventricular fibrillation)

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

• Patients must meet pre-entry requirements

• Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry; women of child-bearing potential must agree to use adequate contraception (two barrier methods of birth control) 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 is to inform her treating physician immediately; all patients must be willing to take contraception up to three months after the final dose of BIBF 1120

Exclusion Criteria:

• Patients who have had prior therapy with BIBF 1120

• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies, are excluded if there is any evidence of other malignancy being present within the last three years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease

• Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last three years are excluded; patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease

• Patients with serious, non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the start date of treatment; patients with underlying lesions that caused the fistula or perforation in the past that have not been corrected

• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels

• Patients with history of brain metastases, or evidence upon physical examination of active central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases

• Uncontrolled hypertension, defined as systolic >= 150 mm Hg or diastolic >= 90 mm Hg

• Myocardial infarction or unstable angina within 6 months of study treatment

• New York Heart Association (NYHA) class II or greater congestive heart failure

• Women with an ejection fraction < institutional lower limit of normal (LLN)

• History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)

• Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater peripheral vascular disease

• History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of study treatment

• Patients undergoing invasive procedures as defined below: major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of treatment; major surgical procedure anticipated during the course of the study; minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of therapy

• Patients who are pregnant or nursing

• Patients with a history of major thromboembolic event defined as: symptomatic pulmonary embolism (PE), recurrent asymptomatic PE, or recurrent deep venous thrombosis

• Prior thrombosis or thromboembolic event due to a known inherited coagulopathy (i.e., antithrombin-III deficiency, protein C or protein S deficiency, factor V Leiden mutation presence, prothrombin G20210A mutation)

• Serious infections requiring systemic antibiotics or antiviral therapy including: known active hepatitis B or C infection; known human immunodeficiency virus (HIV) infection

• Gastrointestinal (GI) or other medical disorders that would impact ingestion or absorption of the drug

• Patients with a history of photosensitivity or who must take agents which increase photosensitivity, e.g. topical retinoids and doxycycline

• Patients who are unable to swallow capsules

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
2	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
3	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
4	Memorial University Medical Center	Savannah	Georgia	United States	31404
5	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
6	Northwestern University	Chicago	Illinois	United States	60611
7	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
8	Sudarshan K Sharma MD Limted-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
9	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
10	Saint Vincent Oncology Center	Indianapolis	Indiana	United States	46260
11	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
12	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
13	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
14	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
15	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
16	Hurley Medical Center	Flint	Michigan	United States	48502
17	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
18	Allegiance Health	Jackson	Michigan	United States	49201
19	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
20	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
21	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
22	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
23	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
24	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
25	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
26	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
27	CoxHealth South Hospital	Springfield	Missouri	United States	65807
28	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
29	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
30	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
31	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
32	Carolinas HealthCare System NorthEast	Concord	North Carolina	United States	28025
33	Akron General Medical Center	Akron	Ohio	United States	44307
34	Case Western Reserve University	Cleveland	Ohio	United States	44106
35	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
36	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
37	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
38	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
39	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
40	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
41	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
42	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
43	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
44	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
45	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
46	Women and Infants Hospital	Providence	Rhode Island	United States	02905
47	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
48	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
49	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
50	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
51	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
52	Northwest Hospital	Seattle	Washington	United States	98133
53	University of Washington Medical Center	Seattle	Washington	United States	98195
54	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
55	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
56	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
57	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
58	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
59	Bay Area Medical Center	Marinette	Wisconsin	United States	54143

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Don Dizon, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT01225887
• Other Study ID Numbers: GOG-0229K; NCI-2011-02657; CDR0000687306; GOG-DTM0906; GOG-0229K; GOG-0229K; GOG-0229K; U10CA180868; U10CA027469
• First Posted: Oct 21, 2010
• Last Update Posted: Oct 9, 2017
• Last Verified: Oct 1, 2016

• Additional relevant MeSH terms: Carcinoma; Adenocarcinoma; Carcinoma, Transitional Cell; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence; Nintedanib

Study Results

Participant Flow

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Period Title: Overall Study
STARTED	37
COMPLETED	32
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.1 (9.8)
Age, Customized (Count of Participants)
30-39 years	1 3.1%
50-59 years	4 12.5%
60-69 years	14 43.8%
70-79 years	10 31.3%
80-89 years	3 9.4%
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	The incidence of adverse events (grade 3 or higher) as assessed by the National Cancer Institute CTCAE version 4.0
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients on study who experienced adverse events (Grade 3 or higher)

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Measure Participants	32
Leukopenia	1 3.1%
Neutropenia	1 3.1%
Anemia	2 6.3%
Other Investigations	4 12.5%
Nausea	2 6.3%
Vomiting	2 6.3%
Other Gastrointestinal	6 18.8%
General & Administration site	3 9.4%
Infections/infestations	1 3.1%
Metabolism/nutrition	1 3.1%
Musculoskeletal/connective tissue	2 6.3%
Psychiatric	2 6.3%
Renal/Urinary	4 12.5%
Respiratory/thoracic/mediastinal	2 6.3%
Vascular Disorders	1 3.1%

2. Primary Outcome

Title	Objective Tumor Response
Description	Complete and Partial Tumor Response by RECIST 1.1
Time Frame	For disease that can be evaluated by physical exam,response was assessed prior to each cycle CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Measure Participants	32
Number (90% Confidence Interval) [percentage of participants]	9.4 29.4%

3. Primary Outcome

Title	Progression-free Survival > 6 Months
Description	Whether or not the patient survived progression-free for at least 6 months.
Time Frame	for disease that can be evaluated by physical exam, progression was assessed prior to each cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Measure Participants	32
Number (90% Confidence Interval) [percentage of participants]	21.9 68.4%

4. Secondary Outcome

Title	Overall Survival
Description	The observed length of life from entry into the study to death or the date of last contact.
Time Frame	From study entry to death or last contact, up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Measure Participants	32
Median (95% Confidence Interval) [months]	10.1

5. Secondary Outcome

Title	Progression Free Survival
Description	the period of progression free survival for patients with persistent or recurrent endometrial cancer treated with study drug.
Time Frame	The duration of time from study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

The time in months that a patient survived progression-free.

Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
Measure Participants	32
Median (90% Confidence Interval) [months]	3.3

Adverse Events

Time Frame	All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Also reported are Serious Adverse Events (SAEs) considered to be treatment related for up to 5 years after stopping study treatment.
Arm/Group Title	Treatment (Nintedanib)
Arm/Group Description	Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
All Cause Mortality
	Treatment (Nintedanib)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Nintedanib)
	Affected / at Risk (%)	# Events
Total	14/32 (43.8%)
Gastrointestinal disorders
Colonic Obstruction	1/32 (3.1%)
Diarrhea	1/32 (3.1%)
Nausea	1/32 (3.1%)
Ascites	1/32 (3.1%)
Jejunal Obstruction	1/32 (3.1%)
General disorders
Fever	1/32 (3.1%)
Infections and infestations
Kidney Infection	1/32 (3.1%)
Investigations
Aspartate Aminotransferase Increased	1/32 (3.1%)
Alanine Aminotransferase Increased	1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Flank Pain	1/32 (3.1%)
Renal and urinary disorders
Urinary Tract Obstruction	1/32 (3.1%)
Acute Kidney Injury	1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/32 (3.1%)
Vascular disorders
Thromboembolic Event	2/32 (6.3%)
Hypertension	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Treatment (Nintedanib)
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Anemia	15/32 (46.9%)
Cardiac disorders
Cardiac Disorders - Other	1/32 (3.1%)
Sinus Tachycardia	2/32 (6.3%)
Ear and labyrinth disorders
Tinnitus	2/32 (6.3%)
Eye disorders
Glaucoma	1/32 (3.1%)
Gastrointestinal disorders
Dyspepsia	1/32 (3.1%)
Dry Mouth	2/32 (6.3%)
Colonic Hemorrhage	1/32 (3.1%)
Constipation	6/32 (18.8%)
Diarrhea	21/32 (65.6%)
Vomiting	13/32 (40.6%)
Abdominal Pain	13/32 (40.6%)
Rectal Hemorrhage	1/32 (3.1%)
Abdominal Distension	3/32 (9.4%)
Nausea	21/32 (65.6%)
Ascites	1/32 (3.1%)
Flatulence	2/32 (6.3%)
Gastritis	1/32 (3.1%)
General disorders
Pain	4/32 (12.5%)
Malaise	1/32 (3.1%)
Non-Cardiac Chest Pain	1/32 (3.1%)
Edema Limbs	3/32 (9.4%)
Fatigue	18/32 (56.3%)
Fever	1/32 (3.1%)
Hepatobiliary disorders
Portal Vein Thrombosis	1/32 (3.1%)
Infections and infestations
Upper Respiratory Infection	1/32 (3.1%)
Skin Infection	1/32 (3.1%)
Esophageal Infection	1/32 (3.1%)
Urinary Tract Infection	1/32 (3.1%)
Investigations
Weight Loss	4/32 (12.5%)
Platelet Count Decreased	3/32 (9.4%)
Lymphocyte Count Decreased	2/32 (6.3%)
Inr Increased	2/32 (6.3%)
Ggt Increased	1/32 (3.1%)
Creatinine Increased	4/32 (12.5%)
Cholesterol High	1/32 (3.1%)
Neutrophil Count Decreased	4/32 (12.5%)
Blood Bilirubin Increased	2/32 (6.3%)
White Blood Cell Decreased	6/32 (18.8%)
Aspartate Aminotransferase Increased	13/32 (40.6%)
Alkaline Phosphatase Increased	11/32 (34.4%)
Alanine Aminotransferase Increased	13/32 (40.6%)
Metabolism and nutrition disorders
Hypophosphatemia	1/32 (3.1%)
Hyponatremia	4/32 (12.5%)
Hypomagnesemia	6/32 (18.8%)
Hypokalemia	7/32 (21.9%)
Hypoglycemia	1/32 (3.1%)
Hypocalcemia	4/32 (12.5%)
Hypoalbuminemia	5/32 (15.6%)
Hyperuricemia	1/32 (3.1%)
Hypertriglyceridemia	1/32 (3.1%)
Hypernatremia	1/32 (3.1%)
Hyperglycemia	9/32 (28.1%)
Dehydration	2/32 (6.3%)
Anorexia	10/32 (31.3%)
Acidosis	1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	3/32 (9.4%)
Myalgia	1/32 (3.1%)
Generalized Muscle Weakness	1/32 (3.1%)
Flank Pain	1/32 (3.1%)
Bone Pain	1/32 (3.1%)
Back Pain	4/32 (12.5%)
Nervous system disorders
Peripheral Sensory Neuropathy	5/32 (15.6%)
Memory Impairment	1/32 (3.1%)
Headache	7/32 (21.9%)
Dysgeusia	2/32 (6.3%)
Dizziness	2/32 (6.3%)
Psychiatric disorders
Insomnia	4/32 (12.5%)
Depression	5/32 (15.6%)
Confusion	1/32 (3.1%)
Anxiety	2/32 (6.3%)
Renal and urinary disorders
Urinary Urgency	1/32 (3.1%)
Urinary Frequency	2/32 (6.3%)
Proteinuria	1/32 (3.1%)
Hematuria	5/32 (15.6%)
Acute Kidney Injury	2/32 (6.3%)
Reproductive system and breast disorders
Vaginal Hemorrhage	2/32 (6.3%)
Dyspareunia	1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Sore Throat	1/32 (3.1%)
Postnasal Drip	2/32 (6.3%)
Pleural Effusion	1/32 (3.1%)
Epistaxis	2/32 (6.3%)
Dyspnea	4/32 (12.5%)
Cough	6/32 (18.8%)
Allergic Rhinitis	1/32 (3.1%)
Adult Respiratory Distress Syndrome	1/32 (3.1%)
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation	1/32 (3.1%)
Rash Acneiform	1/32 (3.1%)
Pruritus	2/32 (6.3%)
Rash Maculo-Papular	1/32 (3.1%)
Alopecia	1/32 (3.1%)
Vascular disorders
Thromboembolic Event	2/32 (6.3%)
Lymphedema	1/32 (3.1%)
Hypertension	5/32 (15.6%)

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.