ABC: Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00479674
• Collaborator: Genentech, Inc. (Industry), Celgene Corporation (Industry)
• Enrollment: 41
• Locations: 4
• Arm: 1
• Duration (Months): 82
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. Monoclonal antibodies including bevacizumab target vascular endothelial growth factor (VEGF) to reduce angiogenesis. We hypothesize that the previously-untested combination of weekly Abraxane® and carboplatin plus biweekly bevacizumab will lengthen time to progression without producing intolerable toxicity.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Abraxane; Drug: Bevacizumab; Drug: Carboplatin	Phase 2

Detailed Description

Anthracycline-based chemotherapy is widely used as adjuvant treatment for breast cancer. In addition to the challenge posed by anthracycline-induced cardiotoxicity, there are issues surrounding previous treatment with anthracyclines which limit its utility in the metastatic disease setting. Many patients with advanced disease will have had prior anthracycline-based adjuvant therapy, may have reached a maximum cumulative lifetime dose, or developed refractory disease, creating an obvious need for non-anthracycline treatment strategies.3 Platinum- and taxane-based chemotherapies as first-line therapy for metastatic breast cancer have demonstrated significant activity, producing single-agent response rates > 50%; in combination these rates increased to > 60% in both previously untreated and in patients who previously received anthracyclines.3 However, overall survival has remained relatively unchanged.4 As there is currently no standard of care for patients with metastatic breast cancer, various physical and psychological factors must be considered when evaluating chemotherapy treatment options, including the patient's tumor biology and growth rate, presence and extent of metastases, history of prior treatment and response, sensitivity and tolerance to therapy, and quality of life.2 Strategies to develop combination, higher dose, or sequential regimens using these active agents, while improving response rates and/or time to progression, may produce increased toxicity without increased survival.2 Because metastatic breast cancer remains essentially incurable using cytotoxic therapy alone, the study of targeted biologics offers new opportunities to enhance drug delivery via their ability to regulate specific receptors that are associated with clinically aggressive disease processes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Abraxane®, Carboplatin and Bevacizumab in "Triple Negative" (Demonstrating No Expression for Estrogen, Progesterone, or Her2 Receptors) Metastatic Breast Cancer
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Abraxane, Carboplatin, Bevacizumab Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15

Drug: Abraxane; 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death..; Other Names: nanoparticle albumin-bound paclitaxel ; Drug: Bevacizumab; 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death.; Other Names: Avastin ; Drug: Carboplatin; area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.

Outcome Measures

Primary Outcome Measures

1. Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III "Triple Negative" Metastatic Breast Cancer. [5 years]

   Best clinical response is based on RECIST criteria, the proportion in each response category along with the exact binomial confidence intervals are estimated. Toxicity summaries are also provided.

Secondary Outcome Measures

1. Median Proportion Progression-free as Estimated by Kaplan-Meier Methods [5 years]

   PFS was defined as time from trial enrollment to disease progression or death, whichever occurred first.

2. To Evaluate Sequential Plasma Samples for Presence of Selected Angiogenic Markers [18 months]

3. to Determine if Apolipoprotein Alleles (Apo-E) Correlate With Treatment-related Neuropathy [18 months]

4. to Determine if SPARC Expression in Breast Tumors Predicts Progression-free Survival (PFS) [18 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Tissue block containing tumor to confirm metastatic breast cancer is required;

• Measurable disease according to RECIST criteria

• "Triple negative" disease defined as tumor demonstrating no expression for estrogen, progesterone or human epidermal growth factor receptor 2(HER2)receptors. "No expression" is categorized as ≤ 10% of cells staining or Allred ≤ 2;

• Aged 18 years or older;

• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1; life expectancy ≥ 3 months;

• Patients may have received 0 - 1 prior therapies (except taxanes in the metastatic setting). An interval of at least 1 week must have elapsed since prior chemotherapy or hormonal therapy for metastatic disease; at least 6 months must have elapsed since prior adjuvant therapy;

• ≥ 2 weeks between surgery and study enrollment (≥ 4 weeks between major surgery (defined as open abdominal/thoracic/cardiac) and study enrollment;

• Laboratory tests performed within 14 days of study entry:

• Granulocytes ≥ 1,500/µL;

• Platelets ≥ 100,000/µL;

• Hemoglobin ≥ 9 gm/dL;

• Total bilirubin ≤ institutional upper limit of normal (ULN);

• Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN;

• Alkaline phosphatase ≤ 2.5 times ULN;

• Estimated creatinine clearance ≥ 60 mL/min.

• left ventricular ejection fraction (LVEF)≥ 50% by multigated acquisition (MUGA)/Echocardiogram;

• Informed consent to receive protocol treatment, to provide biologic specimens, and to complete neurotoxicity questionnaires;

• Cognitive and communication skills to comply with study and/or follow-up procedures;

• No reproductive potential:

• If pre-menopausal: Negative serum pregnancy test and patient agreement to use adequate contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of treatment.

• If post-menopausal: Amenorrhea for ≥ 12 months.

Exclusion Criteria:

• Pregnant or breast feeding;

• Prior treatment with Abraxane®, carboplatin or bevacizumab, or any taxane for metastatic breast cancer;

• Known hypersensitivity to any component of any study drug;

• Active infection;

• Current neuropathy ≥ grade 2;

• central nervous system (CNS) metastases as determined by head CT with contrast;

• History of bleeding within the past 6 months or active bleeding disorder;

• Serious non-healing wound, ulcer or bone fracture;

• Uncontrolled congestive heart failure (CHF), or history of myocardial infarction(MI), unstable angina, stroke, or transient ischemia within previous 6 months;

• Inadequately controlled hypertension (defined as systolic blood pressure < 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications; prior history of hypertensive crisis or hypertensive encephalopathy;

• Proteinuria (defined as urine protein: creatinine (UPC) ratio ≥ 1.0 or urine dipstick ≥ 2+.

• Significant vascular disease (aortic aneurysm, aortic dissection) or symptomatic peripheral vascular disease;

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within previous 6 months;

• Uncontrolled serious contraindicated medical condition or psychiatric illness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Presbyterian Health Care	Charlotte	North Carolina	United States	28204
2	Northeast Oncology Associates	Concord	North Carolina	United States	28205
3	Duke University Medical Center	Durham	North Carolina	United States	27710
4	Forsyth Regional Cancer Center	Winston-Salem	North Carolina	United States	27103-3019

Sponsors and Collaborators

• Duke University
• Genentech, Inc.
• Celgene Corporation

Investigators

• Principal Investigator: Kimberly Blackwell, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Nab- Paclitaxel/Bevacizumab/Carboplatin chemotherapy in the first line triple negative metastatic breast cancer

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00479674
• Other Study ID Numbers: Pro00014837; AVF3962s
• First Posted: May 28, 2007
• Last Update Posted: Feb 18, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Duke University: Metastatic Breast Cancer; Advanced Breast Cancer; Hormone Receptor AND Her2/neu Negative; Triple Negative; Triple Negative Breast Cancer; Stage IV or Inoperable Stage III Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Bevacizumab; Carboplatin; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Period Title: Overall Study
STARTED	41
COMPLETED	0
NOT COMPLETED	41

Baseline Characteristics

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (11)
Sex: Female, Male (Count of Participants)
Female	41 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	12 29.3%
White	25 61%
More than one race	0 0%
Unknown or Not Reported	4 9.8%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III "Triple Negative" Metastatic Breast Cancer.
Description	Best clinical response is based on RECIST criteria, the proportion in each response category along with the exact binomial confidence intervals are estimated. Toxicity summaries are also provided.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

2 subjects withdrew and were not assessed for response

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Measure Participants	39
Complete Response	18 43.9%
Partial Response	69 168.3%
Stable Disease	8 19.5%
Progressive Disease	5 12.2%

2. Secondary Outcome

Title	Median Proportion Progression-free as Estimated by Kaplan-Meier Methods
Description	PFS was defined as time from trial enrollment to disease progression or death, whichever occurred first.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

One subject lost to follow up and not included in analysis.

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Measure Participants	40
Median (95% Confidence Interval) [months]	15

3. Secondary Outcome

Title	To Evaluate Sequential Plasma Samples for Presence of Selected Angiogenic Markers
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Analysis of samples was not performed, as there was inadequate funding to support the testing and analysis of the samples.

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Measure Participants	0

4. Secondary Outcome

Title	to Determine if Apolipoprotein Alleles (Apo-E) Correlate With Treatment-related Neuropathy
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Samples were collected, but analysis was not performed as there was inadequate funding to support the testing and analysis of samples.

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Measure Participants	0

5. Secondary Outcome

Title	to Determine if SPARC Expression in Breast Tumors Predicts Progression-free Survival (PFS)
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Study plan stipulated that tissue samples would not be assessed for quantitatively if no difference in SPARC expression was observed between tumor and non-tumor cells was observed qualitatively.

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Measure Participants	0

Adverse Events

Arm/Group Title	Abraxane, Carboplatin, Bevacizumab
Arm/Group Description	Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15 Abraxane: 100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.. Bevacizumab: 10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death. Carboplatin: area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
All Cause Mortality
	Abraxane, Carboplatin, Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Abraxane, Carboplatin, Bevacizumab
	Affected / at Risk (%)	# Events
Total	22/41 (53.7%)
Blood and lymphatic system disorders
Anemia	1/41 (2.4%)
Gastrointestinal disorders
Dyspepsia	1/41 (2.4%)
Mucositis oral	1/41 (2.4%)
Nausea	3/41 (7.3%)
Vomiting	1/41 (2.4%)
General disorders
Pain	3/41 (7.3%)
Immune system disorders
Allergic reaction	1/41 (2.4%)
Infections and infestations
Infections and infestations - Other, specify:	1/41 (2.4%)
Injury, poisoning and procedural complications
Vascular access complication	3/41 (7.3%)
Investigations
Alanine aminotransferase increased	1/41 (2.4%)
Aspartate aminotransferase increased	1/41 (2.4%)
Neutrophil count decreased	3/41 (7.3%)
Platelet count decreased	4/41 (9.8%)
Metabolism and nutrition disorders
Dehydration	1/41 (2.4%)
Hypokalemia	1/41 (2.4%)
Nervous system disorders
Headache	2/41 (4.9%)
Nervous system disorders - Other, specify: Leptomeningeal Carcinomatosis	1/41 (2.4%)
Peripheral motor neuropathy	1/41 (2.4%)
Peripheral sensory neuropathy	2/41 (4.9%)
Psychiatric disorders
Insomnia	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/41 (2.4%)
Pleural effusion	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders - Other, specify: epistaxis	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Pruritus	1/41 (2.4%)
Skin and subcutaneous tissue disorders - Other, specify: scalp discoloration	1/41 (2.4%)
Vascular disorders
Hypertension	1/41 (2.4%)
Thromboembolic event	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Abraxane, Carboplatin, Bevacizumab
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Anemia	20/41 (48.8%)
Blood and lymphatic system disorders - Other, specify: Anemia	1/41 (2.4%)
Blood and lymphatic system disorders - Other, specify: upper extremity lymphedema	1/41 (2.4%)
Febrile neutropenia	1/41 (2.4%)
Hemolysis	1/41 (2.4%)
Lymph node pain	2/41 (4.9%)
Cardiac disorders
Cardiac disorders - Other, specify: Palpitations	1/41 (2.4%)
Palpitations	2/41 (4.9%)
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify: Ringing in ears	3/41 (7.3%)
Tinnitus	6/41 (14.6%)
Endocrine disorders
Hypothyroidism	1/41 (2.4%)
Eye disorders
Blurred vision	6/41 (14.6%)
Conjunctivitis	1/41 (2.4%)
Extraocular muscle paresis	2/41 (4.9%)
Eye disorders - Other, specify: vision changes	3/41 (7.3%)
Flashing lights	1/41 (2.4%)
Watering eyes	2/41 (4.9%)
Gastrointestinal disorders
Abdominal pain	8/41 (19.5%)
Anal fistula	1/41 (2.4%)
Anal hemorrhage	1/41 (2.4%)
Anal mucositis	2/41 (4.9%)
Colitis	1/41 (2.4%)
Constipation	25/41 (61%)
Diarrhea	15/41 (36.6%)
Dry mouth	3/41 (7.3%)
Dyspepsia	8/41 (19.5%)
Dysphagia	2/41 (4.9%)
Esophageal pain	1/41 (2.4%)
Esophagitis	1/41 (2.4%)
Gastritis	2/41 (4.9%)
Gastrointestinal disorders - Other, specify: dyspepsia	1/41 (2.4%)
Hemorrhoids	4/41 (9.8%)
Mucositis oral	20/41 (48.8%)
Nausea	26/41 (63.4%)
Oral pain	1/41 (2.4%)
Rectal fistula	1/41 (2.4%)
Rectal hemorrhage	1/41 (2.4%)
Rectal pain	1/41 (2.4%)
Vomiting	10/41 (24.4%)
General disorders
Chills	2/41 (4.9%)
Edema face	1/41 (2.4%)
Edema limbs	8/41 (19.5%)
Edema trunk	1/41 (2.4%)
Facial pain	1/41 (2.4%)
Fatigue	34/41 (82.9%)
Fever	2/41 (4.9%)
General disorders and administration site conditions - Other, specify: mouth sores	7/41 (17.1%)
Non-cardiac chest pain	4/41 (9.8%)
Pain	16/41 (39%)
Immune system disorders
Allergic reaction	3/41 (7.3%)
Cytokine release syndrome	1/41 (2.4%)
Infections and infestations
Anorectal infection	1/41 (2.4%)
Bladder infection	1/41 (2.4%)
Infections and infestations - Other, specify:	1/41 (2.4%)
Infections and infestations - Other, specify:	1/41 (2.4%)
Infections and infestations - Other, specify: URI/Sinusitis/laryngitis	2/41 (4.9%)
Sinusitis	3/41 (7.3%)
Tooth infection	2/41 (4.9%)
Upper respiratory infection	1/41 (2.4%)
Urinary tract infection	4/41 (9.8%)
Injury, poisoning and procedural complications
Bruising	1/41 (2.4%)
Tracheal hemorrhage	3/41 (7.3%)
Wound dehiscence	1/41 (2.4%)
Investigations
Alanine aminotransferase increased	5/41 (12.2%)
Alkaline phosphatase increased	6/41 (14.6%)
Aspartate aminotransferase increased	4/41 (9.8%)
Blood bilirubin increased	2/41 (4.9%)
Creatinine increased	1/41 (2.4%)
INR increased	1/41 (2.4%)
Investigations - Other, specify: hypokalemia	1/41 (2.4%)
Neutrophil count decreased	31/41 (75.6%)
Platelet count decreased	18/41 (43.9%)
Weight gain	2/41 (4.9%)
Weight loss	4/41 (9.8%)
White blood cell decreased	8/41 (19.5%)
Metabolism and nutrition disorders
Anorexia	17/41 (41.5%)
Dehydration	2/41 (4.9%)
Hyperglycemia	4/41 (9.8%)
Hypoalbuminemia	5/41 (12.2%)
Hypocalcemia	6/41 (14.6%)
Hypoglycemia	1/41 (2.4%)
Hypokalemia	6/41 (14.6%)
Hypomagnesemia	1/41 (2.4%)
Hyponatremia	5/41 (12.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/41 (22%)
Back pain	10/41 (24.4%)
Bone pain	8/41 (19.5%)
Chest wall pain	6/41 (14.6%)
Fibrosis deep connective tissue	2/41 (4.9%)
Generalized muscle weakness	3/41 (7.3%)
Musculoskeletal and connective tissue disorder - Other, specify: Cramping in Left Calf	3/41 (7.3%)
Myalgia	4/41 (9.8%)
Neck pain	2/41 (4.9%)
Pain in extremity	9/41 (22%)
Nervous system disorders
Ataxia	2/41 (4.9%)
Dizziness	6/41 (14.6%)
Dysgeusia	12/41 (29.3%)
Extrapyramidal disorder	2/41 (4.9%)
Glossopharyngeal nerve disorder	1/41 (2.4%)
Headache	16/41 (39%)
Memory impairment	2/41 (4.9%)
Nervous system disorders - Other, specify: Leptomeningeal Carcinomatosis	2/41 (4.9%)
Olfactory nerve disorder	1/41 (2.4%)
Peripheral motor neuropathy	5/41 (12.2%)
Peripheral sensory neuropathy	23/41 (56.1%)
Sinus pain	2/41 (4.9%)
Tremor	2/41 (4.9%)
Psychiatric disorders
Anxiety	11/41 (26.8%)
Depression	11/41 (26.8%)
Insomnia	16/41 (39%)
Personality change	1/41 (2.4%)
Renal and urinary disorders
Proteinuria	2/41 (4.9%)
Urinary frequency	2/41 (4.9%)
Urinary incontinence	1/41 (2.4%)
Urinary tract pain	1/41 (2.4%)
Urine discoloration	2/41 (4.9%)
Reproductive system and breast disorders
Breast pain	5/41 (12.2%)
Ovulation pain	1/41 (2.4%)
Vaginal dryness	2/41 (4.9%)
Vaginal hemorrhage	1/41 (2.4%)
Vaginal pain	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	9/41 (22%)
Bronchospasm	1/41 (2.4%)
Cough	16/41 (39%)
Dyspnea	14/41 (34.1%)
Epistaxis	11/41 (26.8%)
Pharyngolaryngeal pain	4/41 (9.8%)
Pulmonary hypertension	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders - Other, specify: epistaxis	6/41 (14.6%)
Sinus disorder	10/41 (24.4%)
Voice alteration	10/41 (24.4%)
Skin and subcutaneous tissue disorders
Alopecia	20/41 (48.8%)
Dry skin	8/41 (19.5%)
Hyperhidrosis	2/41 (4.9%)
Nail loss	8/41 (19.5%)
Pain of skin	1/41 (2.4%)
Pruritus	4/41 (9.8%)
Rash acneiform	3/41 (7.3%)
Rash maculo-papular	10/41 (24.4%)
Skin and subcutaneous tissue disorders - Other, specify: scalp discoloration	11/41 (26.8%)
Skin hyperpigmentation	5/41 (12.2%)
Skin hypopigmentation	1/41 (2.4%)
Skin ulceration	3/41 (7.3%)
Vascular disorders
Flushing	4/41 (9.8%)
Hot flashes	14/41 (34.1%)
Hypertension	5/41 (12.2%)
Lymphedema	2/41 (4.9%)
Vascular disorders - Other, specify: Nose bleed	5/41 (12.2%)

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.