Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01267253
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 31
• Locations: 43
• Arm: 1
• Actual Duration (Months): 34.9
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well brivanib alaninate works in treating patients with cervical cancer that has come back. Brivanib alaninate 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
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Persistent Disease; Recurrent Cervical Carcinoma	Drug: Brivanib Alaninate; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the proportion of patients with persistent or recurrent cervical cancer, who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial), treated with brivanib (brivanib alaninate).

2. To determine the nature and degree of toxicity of brivanib 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 cervical cancer treated with brivanib.

TERTIARY OBJECTIVES:

1. To obtain the serum expression levels of surrogate markers of brivanib effects including angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) and markers of endothelial damage (E-selectin, vascular cell adhesion molecule 1 [VCAM-1], and (intercellular adhesion molecule 1 [ICAM-1]). (exploratory) II. To determine whether these marker expression levels alone or in combination are associated with response, PFS, or overall survival. (exploratory)

OUTLINE:

Patients receive brivanib alaninate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, 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: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Brivanib (BMS582664) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix (BMS Study CA182-048)
• Actual Study Start Date: Apr 4, 2011
• Actual Primary Completion Date: Feb 28, 2014
• Actual Study Completion Date: Feb 28, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (brivanib alaninate) Patients receive brivanib alaninate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Brivanib Alaninate; Given PO; Other Names: BMS 582664 BMS-582664 ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Tumor Response [Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.]

   Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1

2. PFS for at Least 6 Months Without Non-protocol Therapy From Study Entry. [Every other cycle for first 6 months; then every 3 months therafter until disease progression confirmed; and at any other time if cliniclly indicated based on symptoms or physical signs suggestive of progressive disease]

   Proportion of participants who survive progression-free for at least 6 months without non-protocol therapy from study entry. Progression is assessed by RECIST 1.1.

3. Adverse Events (Grade 3 or Higher) During Treatment Period [During treatment period and up to 30 days after stopping the study treatment.]

   Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v.4.0

Secondary Outcome Measures

1. Progression-free Survival [From study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up]

   Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1

2. Overall Survival [From study entry to time of death or the date of last contact, up to 5 years of follow-up.]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact..

Other Outcome Measures

1. Serum Expression Levels of Surrogate Markers of Brivanib Alaninate Effects Including Angiogenic Factors (VEGF and bFGF) and Markers of Endothelial Damage (E-selectin, VCAM-1, and ICAM-1) [Up to 5 years]

   Surrogate markers will be associated with response, PFS, and OS.

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 persistent or recurrent squamous cell carcinoma, adenosquamous carcinoma, adenocarcinoma, or non-squamous cell carcinoma of the cervix with documented disease progression (disease not amenable to curative therapy); histologic confirmation of the original primary tumor is required via the pathology report

• All patients must have measurable disease, 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 who have received one prior regimen must have a GOG performance status of 0, 1, or 2

• Patients who have received two prior regimens must have a GOG performance status of 0 or 1

• 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 [UTI])

• 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

• At least 4 weeks must have elapsed from the time of any major surgical procedure

• Patients must have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix; chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen for management of advanced, metastatic, or recurrent disease (e.g.; paclitaxel and carboplatin for up to 4 cycles)

• 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

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

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

• Hemoglobin >= 9 g/dl

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

• Urinalysis needs to be assessed at baseline and proteinuria must be less than or equal to 2+ by dipstick

• If the urine dipstick is > 2+, a 24-hour protein level can be done, as clinically indicated by the investigator

• The 24-hour protein level must be less than or equal to 3.5 g/24 hours

• Bilirubin less than or equal to 1.5 x ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x ULN

• Alkaline phosphatase less than or equal to 2.5 x ULN

• Albumin greater than or equal to 2.5 g/dl

• Neuropathy (sensory and motor) less than or equal to grade 1

• Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN; patients on therapeutic warfarin are excluded from trial, anticoagulation with low molecular weight heparin is allowed

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

• Patients of childbearing potential must have a negative serum pregnancy test performed 48 hours prior to study entry and be practicing an effective form of contraception during the study and for at least 3 months after receiving the final treatment of brivanib

• All patients must have a baseline electrocardiogram completed prior to study entry

• Baseline electrocardiogram (ECG) should be repeated if corrected QT interval (QTc) is found to be > 450 msec; QTc must NOT be > 450 msec on both ECGs performed during the same visit

Exclusion Criteria:

• Patients who have had prior therapy with brivanib or anti-vascular, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy

• 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 the 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 cervical 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 cervical 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 that are on required chronic anti-platelet therapy (aspirin > 300 mg/day, or clopidogrel greater than or equal to 75 mg/day)

• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event >= grade 3 of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) within 30 days prior to study entry

• Patients with a history of poor wound healing, non-healing ulcers, or bone fractures within the last 3 months

• Patients with uncontrolled or significant cardiovascular disease including any of the following:

• Myocardial infarction within 12 months

• Uncontrolled angina within 12 months

• Class III-IV New York Heart Association (NYHA) congestive heart failure

• Uncontrolled hypertension despite anti-hypertensive therapy

• Blood pressure (BP) must be less than or equal to 140/90 at screening

• Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors should be changed to an alternative antihypertensive medication before study entry

• History of stroke, transient ischemic attack (TIA), or other central nervous system (CNS) ischemic event

• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin

• Patients must have pre-therapy left ventricular ejection fraction (LVEF) testing and have an ejection fraction >= institutional lower limit of normal (LLN)

• Patients with valvular heart disease >= grade 2

• Patients with a serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy

• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication

• Patients with hyponatremia (sodium < 130 mEq/L)

• Patients with active/known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; HIV-positive subjects on combination antiretroviral therapy are ineligible

• Patients with known brain metastases

• Patients who are pregnant or nursing

• Patients with inability to swallow tablets or untreated malabsorption syndrome

• Patients with baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to entry study)

• Patients on therapeutic warfarin anticoagulation are excluded

• Patients converted to anticoagulation with low molecular weight heparin will be allowed provided the patient?s PT is such that INR is =< 1.5 x ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
2	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
3	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
4	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
5	The Hospital of Central Connecticut	New Britain	Connecticut	United States	06050
6	Beebe Medical Center	Lewes	Delaware	United States	19958
7	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
8	Florida Hospital Orlando	Orlando	Florida	United States	32803
9	Sarasota Memorial Hospital	Sarasota	Florida	United States	34239
10	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
11	Rush University Medical Center	Chicago	Illinois	United States	60612
12	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
13	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois	United States	60521
14	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
15	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
16	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
17	Baystate Medical Center	Springfield	Massachusetts	United States	01199
18	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan	United States	48106
19	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
20	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
21	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
22	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
23	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
24	CoxHealth South Hospital	Springfield	Missouri	United States	65807
25	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
26	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
27	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
28	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
29	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
30	Case Western Reserve University	Cleveland	Ohio	United States	44106
31	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
32	Kettering Medical Center	Kettering	Ohio	United States	45429
33	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
34	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
35	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
36	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
37	West Penn Hospital	Pittsburgh	Pennsylvania	United States	15224
38	Women and Infants Hospital	Providence	Rhode Island	United States	02905
39	Baylor All Saints Medical Center at Fort Worth	Fort Worth	Texas	United States	76104
40	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
41	M D Anderson Cancer Center	Houston	Texas	United States	77030
42	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
43	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John K Chan, NRG Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT01267253
• Other Study ID Numbers: GOG-0227G; NCI-2011-03814; CDR0000690083; CA182-048; GOG-0227G; GOG-0227G; GOG-0227G; U10CA180868; U10CA027469
• First Posted: Dec 28, 2010
• Last Update Posted: Mar 20, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Recurrence

Study Results

Participant Flow

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Period Title: Overall Study
STARTED	31
COMPLETED	28
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Overall Participants	28
Age, Customized (Count of Participants)
30-39 years	8 28.6%
40-49 years	9 32.1%
50-59 years	7 25%
60-69 years	2 7.1%
70-79 years	2 7.1%
Sex/Gender, Customized (Count of Participants)
Female	28 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Tumor Response
Description	Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1
Time Frame	Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.

Outcome Measure Data

Analysis Population Description

Eligible and Treated participants

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Measure Participants	28
Number (90% Confidence Interval) [proportion]	0.071

2. Primary Outcome

Title	PFS for at Least 6 Months Without Non-protocol Therapy From Study Entry.
Description	Proportion of participants who survive progression-free for at least 6 months without non-protocol therapy from study entry. Progression is assessed by RECIST 1.1.
Time Frame	Every other cycle for first 6 months; then every 3 months therafter until disease progression confirmed; and at any other time if cliniclly indicated based on symptoms or physical signs suggestive of progressive disease

Outcome Measure Data

Analysis Population Description

Eligible and treated participants

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Measure Participants	28
Number (90% Confidence Interval) [proportion]	0.179

3. Primary Outcome

Title	Adverse Events (Grade 3 or Higher) During Treatment Period
Description	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v.4.0
Time Frame	During treatment period and up to 30 days after stopping the study treatment.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Participants

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Measure Participants	28
Leukopenia	0 0%
Thrombocytopenia	0 0%
Neutropenia	0 0%
Anemia	4 14.3%
Other Investigations	4 14.3%
Cardiac Disorders	1 3.6%
Gastrointestinal Disorders	7 25%
General disorders & administration site conditions	2 7.1%
Hepatobiliary Disorders	1 3.6%
Infections and infestations	4 14.3%
Metabolism and nutrition disorders	5 17.9%
Musculoskeletal & connective tissue disorders	3 10.7%
Neoplasms benign, malignant & unspecified	2 7.1%
Nervous system disorders	3 10.7%
Renal and urinary disorders	2 7.1%
Vascular Disorders	5 17.9%

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1
Time Frame	From study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up

Outcome Measure Data

Analysis Population Description

Eligible and Treated Participants

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Measure Participants	28
Median (95% Confidence Interval) [Months]	3.2

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact..
Time Frame	From study entry to time of death or the date of last contact, up to 5 years of follow-up.

Outcome Measure Data

Analysis Population Description

Eligible and Treated Patients

Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
Measure Participants	28
Median (95% Confidence Interval) [Months]	7.9

6. Other Pre-specified Outcome

Title	Serum Expression Levels of Surrogate Markers of Brivanib Alaninate Effects Including Angiogenic Factors (VEGF and bFGF) and Markers of Endothelial Damage (E-selectin, VCAM-1, and ICAM-1)
Description	Surrogate markers will be associated with response, PFS, and OS.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	All adverse events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.
Arm/Group Title	Brivanib
Arm/Group Description	Brivanib 800mg administered orally every day on days 1 to 28 of each cycle until disease progression or adverse effects prohibit further treatment. One cycle is 28 days.
All Cause Mortality
	Brivanib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Brivanib
	Affected / at Risk (%)	# Events
Total	14/28 (50%)
Blood and lymphatic system disorders
Anemia	1/28 (3.6%)
Cardiac disorders
Pulmonary Valve Disease	1/28 (3.6%)
Gastrointestinal disorders
Colonic Hemorrhage	1/28 (3.6%)
Diarrhea	1/28 (3.6%)
Small Intestinal Obstruction	1/28 (3.6%)
Rectal Hemorrhage	1/28 (3.6%)
Mucositis Oral	1/28 (3.6%)
Hepatobiliary disorders
Bile Duct Stenosis	1/28 (3.6%)
Infections and infestations
Sepsis	1/28 (3.6%)
Lung Infection	1/28 (3.6%)
Urinary Tract Infection	1/28 (3.6%)
Metabolism and nutrition disorders
Hyponatremia	1/28 (3.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms Benign, Malignant And Unspecified (Incl	2/28 (7.1%)
Nervous system disorders
Reversible Posterior Leukoencephalopathy Syndrome	1/28 (3.6%)
Renal and urinary disorders
Urinary Tract Obstruction	1/28 (3.6%)
Urinary Retention	1/28 (3.6%)
Vascular disorders
Hypertension	1/28 (3.6%)
Other (Not Including Serious) Adverse Events
	Brivanib
	Affected / at Risk (%)	# Events
Total	28/28 (100%)
Blood and lymphatic system disorders
Anemia	23/28 (82.1%)
Cardiac disorders
Palpitations	1/28 (3.6%)
Left Ventricular Systolic Dysfunction	1/28 (3.6%)
Sinus Tachycardia	2/28 (7.1%)
Ear and labyrinth disorders
Tinnitus	3/28 (10.7%)
Hearing Impaired	2/28 (7.1%)
Endocrine disorders
Hypothyroidism	2/28 (7.1%)
Hyperthyroidism	1/28 (3.6%)
Eye disorders
Eye Disorders - Other	1/28 (3.6%)
Photophobia	1/28 (3.6%)
Blurred Vision	2/28 (7.1%)
Gastrointestinal disorders
Dysphagia	4/28 (14.3%)
Dyspepsia	2/28 (7.1%)
Dry Mouth	2/28 (7.1%)
Constipation	9/28 (32.1%)
Diarrhea	11/28 (39.3%)
Vomiting	15/28 (53.6%)
Bloating	3/28 (10.7%)
Abdominal Pain	10/28 (35.7%)
Rectal Hemorrhage	3/28 (10.7%)
Oral Dysesthesia	1/28 (3.6%)
Mucositis Oral	4/28 (14.3%)
Abdominal Distension	2/28 (7.1%)
Nausea	20/28 (71.4%)
Gastroesophageal Reflux Disease	1/28 (3.6%)
Rectal Pain	1/28 (3.6%)
Toothache	1/28 (3.6%)
Flatulence	1/28 (3.6%)
General disorders
Pain	5/28 (17.9%)
Flu Like Symptoms	1/28 (3.6%)
Non-Cardiac Chest Pain	3/28 (10.7%)
Edema Limbs	4/28 (14.3%)
Fatigue	22/28 (78.6%)
Fever	5/28 (17.9%)
Chills	2/28 (7.1%)
Immune system disorders
Allergic Reaction	1/28 (3.6%)
Infections and infestations
Upper Respiratory Infection	1/28 (3.6%)
Tooth Infection	1/28 (3.6%)
Skin Infection	1/28 (3.6%)
Urinary Tract Infection	5/28 (17.9%)
Abdominal Infection	1/28 (3.6%)
Injury, poisoning and procedural complications
Wound Complication	1/28 (3.6%)
Bruising	1/28 (3.6%)
Investigations
Weight Loss	6/28 (21.4%)
Weight Gain	1/28 (3.6%)
Platelet Count Decreased	8/28 (28.6%)
Lymphocyte Count Decreased	5/28 (17.9%)
Hemoglobin Increased	1/28 (3.6%)
Ejection Fraction Decreased	2/28 (7.1%)
Creatinine Increased	4/28 (14.3%)
Cardiac Troponin T Increased	1/28 (3.6%)
Neutrophil Count Decreased	5/28 (17.9%)
Blood Bilirubin Increased	3/28 (10.7%)
White Blood Cell Decreased	12/28 (42.9%)
Aspartate Aminotransferase Increased	8/28 (28.6%)
Alkaline Phosphatase Increased	7/28 (25%)
Alanine Aminotransferase Increased	7/28 (25%)
Metabolism and nutrition disorders
Hyponatremia	10/28 (35.7%)
Hypomagnesemia	6/28 (21.4%)
Hypokalemia	8/28 (28.6%)
Hypocalcemia	8/28 (28.6%)
Hypoalbuminemia	9/28 (32.1%)
Hypermagnesemia	1/28 (3.6%)
Hyperkalemia	2/28 (7.1%)
Hyperglycemia	8/28 (28.6%)
Hypercalcemia	1/28 (3.6%)
Dehydration	3/28 (10.7%)
Anorexia	15/28 (53.6%)
Musculoskeletal and connective tissue disorders
Pain In Extremity	3/28 (10.7%)
Myalgia	1/28 (3.6%)
Muscle Weakness Lower Limb	1/28 (3.6%)
Joint Range Of Motion Decreased	1/28 (3.6%)
Generalized Muscle Weakness	1/28 (3.6%)
Flank Pain	1/28 (3.6%)
Bone Pain	2/28 (7.1%)
Back Pain	9/28 (32.1%)
Arthritis	2/28 (7.1%)
Arthralgia	1/28 (3.6%)
Nervous system disorders
Seizure	1/28 (3.6%)
Peripheral Sensory Neuropathy	8/28 (28.6%)
Paresthesia	1/28 (3.6%)
Memory Impairment	1/28 (3.6%)
Headache	11/28 (39.3%)
Dizziness	6/28 (21.4%)
Concentration Impairment	2/28 (7.1%)
Aphonia	1/28 (3.6%)
Psychiatric disorders
Insomnia	2/28 (7.1%)
Hallucinations	1/28 (3.6%)
Depression	4/28 (14.3%)
Anxiety	3/28 (10.7%)
Renal and urinary disorders
Urinary Urgency	1/28 (3.6%)
Urinary Tract Obstruction	1/28 (3.6%)
Urinary Retention	2/28 (7.1%)
Urinary Incontinence	1/28 (3.6%)
Urinary Tract Pain	4/28 (14.3%)
Urinary Frequency	6/28 (21.4%)
Proteinuria	6/28 (21.4%)
Hemoglobinuria	1/28 (3.6%)
Hematuria	3/28 (10.7%)
Cystitis Noninfective	1/28 (3.6%)
Chronic Kidney Disease	1/28 (3.6%)
Reproductive system and breast disorders
Reproductive System And Breast Disorders - Other	1/28 (3.6%)
Vaginal Pain	2/28 (7.1%)
Vaginal Hemorrhage	1/28 (3.6%)
Vaginal Dryness	1/28 (3.6%)
Pelvic Pain	2/28 (7.1%)
Vaginal Discharge	2/28 (7.1%)
Respiratory, thoracic and mediastinal disorders
Respiratory, Thoracic And Mediastinal Disorders -	1/28 (3.6%)
Nasal Congestion	1/28 (3.6%)
Hoarseness	2/28 (7.1%)
Dyspnea	7/28 (25%)
Cough	4/28 (14.3%)
Wheezing	1/28 (3.6%)
Allergic Rhinitis	2/28 (7.1%)
Skin and subcutaneous tissue disorders
Skin And Subcutaneous Tissue Disorders - Other	1/28 (3.6%)
Skin Hyperpigmentation	1/28 (3.6%)
Rash Acneiform	1/28 (3.6%)
Pruritus	2/28 (7.1%)
Rash Maculo-Papular	2/28 (7.1%)
Nail Ridging	1/28 (3.6%)
Nail Loss	1/28 (3.6%)
Alopecia	2/28 (7.1%)
Vascular disorders
Superior Vena Cava Syndrome	1/28 (3.6%)
Lymphedema	2/28 (7.1%)
Hypertension	12/28 (42.9%)
Hot Flashes	3/28 (10.7%)

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.