Sunitinib Malate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide Before Surgery in Treating Patients With Stage IIB-IIIC Breast Cancer

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00513695
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 68
• Locations: 7
• Arm: 1
• Duration (Months): 124.5
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving sunitinib malate together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide before surgery works in treating patients with stage IIB-IIIC breast cancer. Sunitinib malate 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. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib malate together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Breast Cancer; Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer	Drug: sunitinib malate; Drug: paclitaxel; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: flow cytometry	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

I.To assess the microscopic pathologic complete response rate (pCR) in patients treated with a two part, neoadjuvant regimen consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed by weekly doxorubicin and daily oral cyclophosphamide given with filgrastim (G-CSF) support for 15 weeks.

SECONDARY OBJECTIVES:

1. To assess the association between microscopic pCR and clinical complete response rate at the primary tumor site.

2. To assess the relapse rate, overall and disease-free survival in patients with breast cancer treated with neoadjuvant chemotherapy consisting of daily oral sunitinib with weekly IV paclitaxel for 12 weeks followed weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 15 weeks.

3. To assess the toxicity associated with these regimens. IV. To explore the relationship between planned correlative laboratory and clinical studies and indicators of efficacy such as pathologic response, clinical response and relapse.

OUTLINE:

Patients receive neoadjuvant chemotherapy comprising sunitinib malate orally (PO) once daily and paclitaxel intravenously (IV) over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim subcutaneously (SC) on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Maleate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Oct 16, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (neoadjuvant chemotherapy before surgery) Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery.

Drug: sunitinib malate; Given PO; Other Names: SU11248 sunitinib Sutent ; Drug: paclitaxel; Given IV; Other Names: Anzatax Asotax TAX Taxol ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Drug: cyclophosphamide; Given PO; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Biological: filgrastim; Given SC; Other Names: G-CSF Neupogen ; Procedure: therapeutic conventional surgery; Undergo surgery; Other: laboratory biomarker analysis; Correlative studies; Other: flow cytometry; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Microscopic Pathologic CR (pCR) Rate [At the time of surgery]

   Defined as no evidence of microscopic invasive tumor present at primary tumor site in the surgical specimen and calculated with exact 90% binomial confidence interval.

Secondary Outcome Measures

1. Clinical Complete Response and Correlation With Plasma VEGF, Soluble VCAM (sVCAM), and Circulating Endothelial Cells (CECs) Levels [At baseline, after week 12 of therapy, and prior to surgery]

2. Relapse Rate [Up to two years]

   Cumulative incidence rate of relapse, assessed at two years. Death is considered a competing risk.

3. Time to Disease Progression [Up to 2 years]

   Median time to disease progression, at two years, as defined by clear increase in disease sites present at registration or development of new disease sites.

4. Overall Survival [Up to 2 years]

   Kaplan-Meier estimate from the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive, assessed at two years.

5. Number and Percent of Subjects Reporting Adverse Events [28 days after the last dose of study drug]

   See Adverse Events section for more details.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be informed of the investigational nature of the study and all pertinent aspects of the trial and must sign and give written consent in accordance with institutional and federal guidelines

• Have a histologically-confirmed diagnosis of breast cancer that is locally advanced or inflammatory; inflammatory breast cancer is defined as erythema and peau d'orange involving half or more of the breast with a histologic diagnosis of breast cancer; the finding of focal dermal lymphatic involvement on histology does not constitute inflammatory breast cancer

• Have selected stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0 or T0-2, N2, M0) disease judged primarily unresectable by an experienced breast surgeon or otherwise deemed appropriate candidates for neoadjuvant treatment or stage IIIB (T4, any N, M0) or stage IIIC (any T, N3, M0) disease

• Patients must have a performance status of 0-2 by Zubrod criteria

• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

• Platelet count >= 100,000 cells/mm^3

• Serum creatinine =< 1.5 x institutional upper limit of normal (IULN)

• Bilirubin =< 2.0

• Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT)/alkaline phosphatase =< 2.0 x IULN

• Have a multi gated acquisition scan (MUGA) or echocardiogram scan performed within 3 months prior to enrollment and have a left ventricular ejection fraction (LVEF) % greater than the institutional lower limit of normal

• Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

Exclusion Criteria:

• Have evidence of distant metastases

• Have tumors that overexpress human epidermal growth factor receptor 2 (HER2)/neu as evidenced by 3+ staining by immunohistochemistry or gene amplification by fluorescent in situ hybridization (FISH)

• Have received any prior chemotherapy or hormonal therapy for breast cancer

• Have received prior radiation therapy or prior definitive surgery for breast cancer

• Have a clinical diagnosis of congestive heart failure or angina pectoris or any of the following within the 6 months prior to study drug administration:, myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

• Have ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 grade >= 2

• Have uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy)

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

• Have a known, active infection

• Have any prior malignancy except for adequately treated basal cell or squamous cell skin cancer, any in situ cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease-free for 5 years

• Human immunodeficiency virus (HIV) positive

• Are receiving or planning to receive any concurrent anticancer therapy while receiving protocol treatment

• Are receiving or planning to receive concurrent treatment on another clinical trial (supportive care trials or non-treatment trials, e.g. quality of life (QOL) are allowed; participation in the companion imaging trial, dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and fludeoxyglucose F 18 positron emission tomography (FDG PET) with Kinetic Analysis to Monitor Breast Cancer Response to Neoadjuvant Sunitinib and Metronomic Chemotherapy is also allowed)

• Be pregnant or breast feeding; female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; all female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment; male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the principal investigator or a designated associate

• Have other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
2	Katmai Oncology Group	Anchorage	Alaska	United States	99508
3	Arizona Cancer Center	Tucson	Arizona	United States	85724-5024
4	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
5	Skagit Valley Hospital	Mount Vernon	Washington	United States	98273
6	Olympic Medical Center	Port Angeles	Washington	United States	98362
7	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jennifer Specht, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Specht, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00513695
• Other Study ID Numbers: 6488; NCI-2010-00607; NCT00831584
• First Posted: Aug 9, 2007
• Last Update Posted: Aug 7, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Breast Neoplasms; Breast Neoplasms, Male; Inflammatory Breast Neoplasms; Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Period Title: Overall Study
STARTED	68
COMPLETED	63
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Overall Participants	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50
Sex: Female, Male (Count of Participants)
Female	68 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 5.9%
Not Hispanic or Latino	56 82.4%
Unknown or Not Reported	8 11.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 5.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 2.9%
White	50 73.5%
More than one race	4 5.9%
Unknown or Not Reported	8 11.8%

Outcome Measures

1. Primary Outcome

Title	Microscopic Pathologic CR (pCR) Rate
Description	Defined as no evidence of microscopic invasive tumor present at primary tumor site in the surgical specimen and calculated with exact 90% binomial confidence interval.
Time Frame	At the time of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	63
Number (95% Confidence Interval) [percent of evaluable participants]	27 39.7%

2. Secondary Outcome

Title	Clinical Complete Response and Correlation With Plasma VEGF, Soluble VCAM (sVCAM), and Circulating Endothelial Cells (CECs) Levels
Time Frame	At baseline, after week 12 of therapy, and prior to surgery

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	0

3. Secondary Outcome

Title	Relapse Rate
Description	Cumulative incidence rate of relapse, assessed at two years. Death is considered a competing risk.
Time Frame	Up to two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	63
Number (95% Confidence Interval) [probability of relapse]	0.215

4. Secondary Outcome

Title	Time to Disease Progression
Description	Median time to disease progression, at two years, as defined by clear increase in disease sites present at registration or development of new disease sites.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	63
Median (95% Confidence Interval) [days]	NA

5. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate from the start of protocol therapy until the date of death from any cause or the last date the patient was known to be alive, assessed at two years.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	63
Number (95% Confidence Interval) [survival probability]	0.875

6. Secondary Outcome

Title	Number and Percent of Subjects Reporting Adverse Events
Description	See Adverse Events section for more details.
Time Frame	28 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
Measure Participants	68
Count of Participants [Participants]	67 98.5%

Adverse Events

Arm/Group Title	Treatment (Neoadjuvant Chemotherapy Before Surgery)
Arm/Group Description	Patients receive neoadjuvant chemotherapy comprising sunitinib malate PO once daily and paclitaxel IV over 1 hour once weekly for 8-12 weeks in the absence of disease progression or unacceptable toxicity. Beginning within 3 weeks of completion of sunitinib malate and paclitaxel, patients receive doxorubicin IV once weekly for 15 weeks, cyclophosphamide PO once daily for 15 weeks, and filgrastim SC on days 2-7 for 16 weeks in the absence of disease progression or unacceptable toxicity. Beginning 3-6 weeks after completion of chemotherapy, patients undergo surgery. sunitinib malate: Given PO paclitaxel: Given IV doxorubicin hydrochloride: Given IV cyclophosphamide: Given PO filgrastim: Given SC therapeutic conventional surgery: Undergo surgery laboratory biomarker analysis: Correlative studies flow cytometry: Correlative studies
All Cause Mortality
	Treatment (Neoadjuvant Chemotherapy Before Surgery)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Neoadjuvant Chemotherapy Before Surgery)
	Affected / at Risk (%)	# Events
Total	47/68 (69.1%)
Blood and lymphatic system disorders
Neutropenia (ANC)	47/68 (69.1%)
Leucopenia	23/68 (33.8%)
Anemia	15/68 (22.1%)
Gastrointestinal disorders
Diarrhea	3/68 (4.4%)
Nausea	1/68 (1.5%)
General disorders
Fatigue	3/68 (4.4%)
Pain	2/68 (2.9%)
Investigations
ALT elevation	4/68 (5.9%)
Nervous system disorders
Sensory Neuropathy	3/68 (4.4%)
Respiratory, thoracic and mediastinal disorders
Mucositis	7/68 (10.3%)
Skin and subcutaneous tissue disorders
Rash	1/68 (1.5%)
Nail changes	2/68 (2.9%)
Other (Not Including Serious) Adverse Events
	Treatment (Neoadjuvant Chemotherapy Before Surgery)
	Affected / at Risk (%)	# Events
Total	67/68 (98.5%)
Blood and lymphatic system disorders
Neutropenia (ANC)	22/68 (32.4%)
Leucopenia	34/68 (50%)
Anemia	32/68 (47.1%)
Gastrointestinal disorders
Diarrhea	9/68 (13.2%)
Heartburn	8/68 (11.8%)
Nausea	8/68 (11.8%)
General disorders
Fatigue	37/68 (54.4%)
Pain	15/68 (22.1%)
Investigations
ALT elevation	6/68 (8.8%)
Nervous system disorders
Sensory Neuropathy	4/68 (5.9%)
Psychiatric disorders
Mood alteration	7/68 (10.3%)
Respiratory, thoracic and mediastinal disorders
Mucositis	5/68 (7.4%)
Skin and subcutaneous tissue disorders
Rash	8/68 (11.8%)
Nail changes	12/68 (17.6%)
Vascular disorders
Hypertension	8/68 (11.8%)

Limitations/Caveats

[Not Specified]

More Information

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.