Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00071058
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 73
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will examine the safety and effectiveness of treating adrenocortical cancer with combination chemotherapy using doxorubicin, vincristine, and etoposide in addition to the drugs mitotane and tariquidar and, when possible, surgery. Adrenocortical cancer cells have a large amount of a protein called P-glycoprotein that "pumps" anti-cancer drugs out of the cells, decreasing their effectiveness. Continuous infusions of doxorubicin, vincristine, and etoposide may improve chemotherapy results by blocking the P-glycoprotein pump, as may use of tariquidar, an experimental drug that is known to block the P-glycoprotein pump.

Patients 18 years of age and older with adrenocortical cancer that has recurred, spread, or cannot be treated surgically may be eligible for this study. Candidates will be screened with a medical history and physical examination; review of pathology slides; blood tests; electrocardiogram (EKG); imaging tests, including computed tomography (CT) of the chest, abdomen and pelvis; chest x-ray; and possibly a bone scan or other imaging tests needed to evaluate the cancer, urine studies, and an echocardiogram. Also, a biopsy (removal of a small sample of tumor tissue) may be required if a specimen is not available to confirm the cancer.

Participants will undergo the following tests and procedures:

• Tumor biopsy. Before starting chemotherapy, a small piece of tumor is removed to study the P-glycoprotein pump and to determine the tumor genetics.

• Blood draw. Blood is drawn before treatment begins to establish baseline levels for future blood tests.

• Central venous catheter placement. A specially trained physician places a plastic tube into a major vein in the chest. The tube is used to give the study drugs and other medications and to withdraw blood samples. It can stay in the body for months or be removed after each treatment is completed. The tube placement is done under a local anesthetic in the radiology department or operating room.

• Chemotherapy. Treatment cycles are 21 days. Doxorubicin, vincristine, and etoposide are given through the central venous catheter by an infusion pump continuously over 96 hours starting day 1 of each cycle. The dose of these drugs may be increased or decreased from cycle to cycle, based on side effects. Mitotane is given in pill form starting day 1 of cycle 1 and is taken every day throughout the entire study. The mitotane dose is gradually increased as long as the side effects are tolerable. Tariquidar is given through the central venous catheter as a 30-minute infusion on days 1 and 3 of every cycle. The tariquidar dose remains the same throughout the study. Treatment will continue for two cycles after all the cancer is gone, or until surgery is done to remove some or all of the remaining cancer, or, if surgery is not an option, until the cancer has grown to where it is defined as progressive disease.

• Nuclear scans. A nuclear scan is done before treatment begins and again on day 1 or day 3 of the first treatment cycle after administration of tariquidar to evaluate the P glycoprotein response to treatment.

• Computed tomography (CT) scans. These scans are done every two treatment cycles to follow disease progress.

• Surgery. Surgery to remove areas of cancer may be considered at any point during the study (including before beginning treatment), if it is deemed beneficial. Treatment with the study drugs will begin or resume after surgery. The length of treatment will depend on the response to treatment before the surgery and on whether there is any cancer remaining after the surgery.

Condition or Disease	Intervention/Treatment	Phase
Adrenal Cortex Neoplasms	Drug: XR9576 (Tariquidar)	Phase 2

Detailed Description

Adrenocortical cancer (ACC) is a rare tumor that is optimally treated with surgical resection. However, many patients present with unresectable disease and relapses are common after surgical resection creating a need for more effective systemic therapies. Several investigators have reported responses to a variety of chemotherapy agents, without a clear improvement in overall survival. A possible explanation for these disappointing results is the high levels of expression of P-glycoprotein (Pgp) seen in a majority of adrenocortical cancers. Pgp, a membrane protein that can function as a drug efflux pump lowering the intracellular concentrations of various drugs, has been implicated as a mechanism of drug resistance.

A prior National Cancer Institute (NCI) study (referred to as MAVE) tried to improve response rates by using a combined modality approach with chemotherapy and surgery. Prior in vitro studies had shown that mitotane inhibited Pgp and that continuous exposure to doxorubicin and vincristine was more effective at overcoming Pgp-mediated resistance than the same drugs given on an intermittent schedule. The MAVE study used daily oral mitotane with infusional doxorubicin, vincristine, and etoposide prior to tumor resection in patients with resectable or potentially resectable tumors. The results showed an overall response rate of 19% (including minor responses), and an overall median survival of 13.5 months. These results were similar to those reported with previous regimens in adrenocortical cancer (ACC). A possible explanation for the failure to achieve a higher response rate may be that mitotane was unable to inhibit Pgp. Although the serum levels of mitotane achieved in patients had been shown to block Pgp in vitro, inhibition of Pgp in patients was not accomplished, as documented by a validated surrogate assay using Pgp-expressing CD56+ cells and the Pgp substrate, rhodamine. Thus the question of whether Pgp inhibition would improve response rates remains unanswered.

This trial will attempt to answer the latter question by using an agent, tariquidar (XR9576), which has been proven to inhibit Pgp in humans with minimal toxicity alone or in combination with chemotherapy. Tariquidar will be used with the regimen from the prior MAVE study in an effort to improve response rates and overall survival in patients with ACC whose options at this time are limited.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study of Combination Chemotherapy & Surgical Resection in the Tx of Adrenocortical Cancer: Mitotane & Continuous Infusion Doxorubicin, Vincristine & Etoposide w/the P-glycoprotein Antagonist, Tariquidar (XR9576), Before & After Surgical Resection
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Surgery plus chemotherapy Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m^2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.

Drug: XR9576 (Tariquidar); Other Names: 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Partial or Complete Response [Every 6 weeks for up to a year]

   Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all signs and symptoms of tumor for a period of at least 4 weeks. Partial response is defined as at least a 30% decrease in the sum of the longest diameter of all measured lesions lasting for a period of 4 weeks.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [60 months, 19 days]

   Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Eligibility Criteria

Criteria

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

• INCLUSION CRITERIA:

Pathologic confirmation of adrenocortical cancer by the Laboratory of Pathology, NCI

Diagnosis of recurrent, metastatic, or primary unresectable adrenocortical carcinoma.

Measurable disease at presentation.

A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

Age greater than or equal to 18 years.

Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date.

Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation.

Prior mitotane therapy is allowed. Patients do not need to be off mitotane therapy prior to starting this protocol.

Organ and marrow function as defined below:

• Total bilirubin less than or equal to 1.5 times ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome,

• Aspartate aminotransferase (AST) less than or equal to 3 times ULN, Alanine aminotransferase (ALT) less than or equal to 3 times ULN

• Creatinine clearance greater than or equal to 40 ml/min (measured in a timed urine collection) or serum creatinine less than or equal to 1.6 mg/dl

• Absolute neutrophil count greater than or equal to 1000/mm^3,

• Platelet count greater than or equal to 100,000/mm^3

Ability to understand and sign an informed consent document.

Ability and willingness to follow the guidelines of the clinical protocol including visits to National Cancer Institute (NCI), Bethesda, Maryland for treatment and follow up visits.

The effects of chemotherapy on the developing human fetus are potentially harmful therefore women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier methods) during the study and for a period of 1 month after the last dose of chemotherapy.

EXCLUSION CRITERIA:

Patients with adrenocortical tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants.

Uncontrolled illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, seizure disorder, or psychiatric illness that may limit compliance with study requirements. These illnesses may be exacerbated by chemotherapy.

Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.

Pregnancy due to the possible adverse effects on the developing fetus.

Lactating women who are breast-feeding due to the possibility of transmitting chemotherapy to the child.

The presence of a second malignancy, other than squamous cell carcinoma of the skin or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study.

Currently receiving treatment (which cannot be discontinued) with the following agents:

diltiazem, nicardipine, phenothiazines, phenytoin, or verapamil because these are Pgp inhibitors and will interfere with the primary objective of the study.

Ejection fraction less than 40% as determined by multi-gated acquisition scan (MUGA), echocardiogram (Echo), or cardiac magnetic resonance imaging (MRI) in patients with a clinical history suggestive of systolic dysfunction.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Institute (NCI)	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Antonio Fojo, M.D., National Cancer Institute, National Institutes of Health

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Cohn K, Gottesman L, Brennan M. Adrenocortical carcinoma. Surgery. 1986 Dec;100(6):1170-7.

• ClinicalTrials.gov Identifier: NCT00071058
• Other Study ID Numbers: 040011; 04-C-0011; NCT00073996
• First Posted: Oct 10, 2003
• Last Update Posted: Sep 18, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by , ,: P-glycoprotein Inhibition; Drug Resistance Reversal; Pharmacodynamics; Molecular Target; Endocrine Cancer; Adrenocortical Cancer; ACC; Adrenocortical Tumor
• Additional relevant MeSH terms: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma

Study Results

Participant Flow

Arm/Group Title	Surgery Plus Chemotherapy
Arm/Group Description	Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m^2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
Period Title: Overall Study
STARTED	50
COMPLETED	49
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Surgery Plus Chemothrapy
Arm/Group Description	Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
Overall Participants	50
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	49 98%
>=65 years	1 2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.56 (12.2)
Sex: Female, Male (Count of Participants)
Female	37 74%
Male	13 26%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2%
Not Hispanic or Latino	48 96%
Unknown or Not Reported	1 2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 6%
White	46 92%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Partial or Complete Response
Description	Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all signs and symptoms of tumor for a period of at least 4 weeks. Partial response is defined as at least a 30% decrease in the sum of the longest diameter of all measured lesions lasting for a period of 4 weeks.
Time Frame	Every 6 weeks for up to a year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgery Plus Chemotherapy
Arm/Group Description	Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
Measure Participants	49
Complete Response	4 8%
Partial Response	6 12%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time Frame	60 months, 19 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Surgery Plus Chemotherapy
Arm/Group Description	Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m^2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
Measure Participants	49
Number [Participants]	49 98%

Adverse Events

Arm/Group Title	Surgery Plus Chemothrapy
Arm/Group Description	Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy. Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
All Cause Mortality
	Surgery Plus Chemothrapy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Surgery Plus Chemothrapy
	Affected / at Risk (%)	# Events
Total	13/50 (26%)
Blood and lymphatic system disorders
Leukocytes (total WBC)	1/50 (2%)	1
Neutrophils/granulocytes (ANC/AGC)	3/50 (6%)	3
Cardiac disorders
Cardiac left ventricular function	1/50 (2%)	1
Cardiac-ischemia/infarction	1/50 (2%)	2
Thrombosis/embolism	2/50 (4%)	2
Gastrointestinal disorders
Anorexia	1/50 (2%)	1
Constipation	3/50 (6%)	3
Dehydration	1/50 (2%)	1
Diarrhea patients without colostomy	1/50 (2%)	1
Dysphagia, esophagitis, odynophagia (painful swallowing)	1/50 (2%)	1
Ileus (or neuroconstipation)	1/50 (2%)	1
Nausea	5/50 (10%)	5
Vomiting	3/50 (6%)	3
Abdominal pain or cramping	2/50 (4%)	2
General disorders
Fatigue (lethargy, malaise, asthenia)	1/50 (2%)	1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	5/50 (10%)	5
Rigors/chills	1/50 (2%)	1
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/50 (2%)	1
Infections and infestations
Febrile Neutropenia	2/50 (4%)	2
Infection	1/50 (2%)	1
Infection without neutropenia	1/50 (2%)	1
Metabolism and nutrition disorders
Hyponatremia	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/50 (2%)	1
Other (Not Including Serious) Adverse Events
	Surgery Plus Chemothrapy
	Affected / at Risk (%)	# Events
Total	49/50 (98%)
Blood and lymphatic system disorders
Hemoglobin	47/50 (94%)	176
Leukocytes (total WBC)	34/50 (68%)	62
Neutrophils/granulocytes (ANC/AGC)	45/50 (90%)	101
Platelets	33/50 (66%)	109
Prothrombin time (PT)	1/50 (2%)	1
Hematuria (in the absence of vaginal bleeding)	2/50 (4%)	2
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	1/50 (2%)	1
Vaginal bleeding	2/50 (4%)	2
Cardiac disorders
Palpitations	1/50 (2%)	1
Sinus tachycardia	1/50 (2%)	1
Vasovagal episode	1/50 (2%)	1
Cardiac left ventricular function	1/50 (2%)	1
Edema	6/50 (12%)	6
Hypertension	1/50 (2%)	1
Hypotension	1/50 (2%)	1
Peripheral arterial ischemia	1/50 (2%)	1
Thrombosis/embolism	4/50 (8%)	4
Ear and labyrinth disorders
Earache (otalgia)	1/50 (2%)	1
Endocrine disorders
Hot flashes/flushes	4/50 (8%)	6
Eye disorders
Cataract	1/50 (2%)	1
Conjunctivitis	1/50 (2%)	1
Dry eye	1/50 (2%)	1
Tearing (watery eyes)	2/50 (4%)	2
Vision-blurred vision	4/50 (8%)	4
Vision-flashing lights/floaters	1/50 (2%)	1
Gastrointestinal disorders
Anorexia	33/50 (66%)	56
Constipation	28/50 (56%)	45
Dehydration	6/50 (12%)	8
Diarrhea patients without colostomy	28/50 (56%)	56
Dyspepsia/heartburn	8/50 (16%)	9
Dysphagia, esophagitis, odynophagia (painful swallowing)	4/50 (8%)	7
Flatulence	3/50 (6%)	3
Ileus (or neuroconstipation)	1/50 (2%)	1
Nausea	42/50 (84%)	91
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	30/50 (60%)	61
Taste disturbance (dysgeusia)	10/50 (20%)	16
Vomiting	30/50 (60%)	54
Abdominal pain or cramping	19/50 (38%)	29
Rectal or perirectal pain (proctalgia)	1/50 (2%)	1
Gastrointestinal-Other (Specify, dental extraction; early satiety; bloating)	3/50 (6%)	3
General disorders
Fatigue (lethargy, malaise, asthenia)	44/50 (88%)	111
Fever	12/50 (24%)	13
Rigors, chills	1/50 (2%)	1
Sweating (diaphoresis)	3/50 (6%)	4
Weight loss	11/50 (22%)	15
Chest pain (non-cardiac and non-pleuritic)	2/50 (4%)	2
Pain-Other (Specify, Back Pain; Neck; Flank R; Pain in right rib )	4/50 (8%)	4
Hepatobiliary disorders
Alkaline phosphatase	13/50 (26%)	22
Bilirubin	4/50 (8%)	4
Hypoalbuminemia	25/50 (50%)	55
SGOT (AST) (serum glutamic oxaloacetic transaminase)	26/50 (52%)	58
SGPT (ALT) (serum glutamic pyruvic transaminase)	23/50 (46%)	52
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	3/50 (6%)	3
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	9/50 (18%)	11
Infections and infestations
Catheter-related infection	1/50 (2%)	1
Febrile neutropenia	3/50 (6%)	3
Infection	2/50 (4%)	2
Infection without neutropenia	16/50 (32%)	29
Infection/Febrile Neutropenia-Other (Specify, vag. yeast infection)	3/50 (6%)	4
Metabolism and nutrition disorders
Hypercalcemia	1/50 (2%)	3
Hyperglycemia	1/50 (2%)	1
Hyperkalemia	1/50 (2%)	1
Hypermagnesemia	1/50 (2%)	1
Hypernatremia	1/50 (2%)	2
Hypocalcemia	5/50 (10%)	5
Hypokalemia	23/50 (46%)	44
Hypomagnesemia	9/50 (18%)	15
Hyponatremia	17/50 (34%)	22
Musculoskeletal and connective tissue disorders
Muscle weakness (not due to neuropathy)	9/50 (18%)	10
Musculoskeletal-Other (Specify, fracture of L. fibula)	1/50 (2%)	1
Arthralgia (joint pain)	33/50 (66%)	93
Bone pain	2/50 (4%)	3
Myalgia (muscle pain)	11/50 (22%)	18
Nervous system disorders
Ataxia (incoordination)	4/50 (8%)	4
Confusion	5/50 (10%)	5
Dizziness/lightheadedness	7/50 (14%)	9
Insomnia	6/50 (12%)	8
Mood alteration-anxiety, agitation	2/50 (4%)	2
Mood alteration-depression	3/50 (6%)	5
Neurology-Other (Specify, largyngitis, voice hoarseness; neurology: Tinnitus L>R )	2/50 (4%)	2
Neuropathy - motor	2/50 (4%)	2
Neuropathy-sensory	29/50 (58%)	48
Headache	9/50 (18%)	12
Renal and urinary disorders
Proteinuria	1/50 (2%)	1
Urinary frequency/urgency	3/50 (6%)	4
Urinary retention	5/50 (10%)	5
Reproductive system and breast disorders
Vaginitis (not due to infection)	1/50 (2%)	1
Sexual/Reproductive Function-Other (Specify, Amenorrhea)	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders
Pleuritic pain	1/50 (2%)	1
Cough	3/50 (6%)	3
Dyspnea (shortness of breath)	12/50 (24%)	14
Hypoxia	1/50 (2%)	1
Pneumothorax	1/50 (2%)	1
Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis)	3/50 (6%)	4
Skin and subcutaneous tissue disorders
Alopecia	34/50 (68%)	37
Bruising (in absence of grade 3 or 4 thrombocytopenia)	2/50 (4%)	2
Hand-foot skin reaction	3/50 (6%)	6
Nail changes	1/50 (2%)	1
Pigmentation changes (e.g., vitiligo)	1/50 (2%)	1
Rash/desquamation	8/50 (16%)	9
Dermatology/Skin-Other (Specify, Head Rash; pain: port problems, pain, redness )	2/50 (4%)	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.