Doxorubicin (Doxil) Combined With Rituxan, Cyclophosphamide, Vincristine and Prednisone in Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas

• Sponsor: University of Southern California (Other)
• Overall Status: Completed
• CT.gov ID: NCT00184002
• Collaborator: Ortho Biotech, Inc. (Industry)
• Enrollment: 68
• Location: 1
• Arm: 1
• Actual Duration (Months): 123.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The current standard treatment for non-Hodgkin's lymphoma involves drugs called cyclophosphamide, doxorubicin, vincristine, prednisone and rituxan in a regimen called "R-CHOP." Using R-CHOP therapy, complete disappearance of disease is expected in over 50% of people. One of the active drugs in the R-CHOP regimen, doxorubicin, has previously been reformulated and been placed in a fatty bubble called a liposome. The reason for placing the drug in the liposome is that there is evidence that the liposome is better taken up by tumors. This liposomally encapsulated form of doxorubicin called Doxil has shown similar or better anti-tumor against certain tumors with reduced side effects. Doxil is FDA approved for ovarian cancer. However its use in non-Hodgkin's lymphoma is still investigational. By substituting Doxil for doxorubicin in the R-CHOP regimen, it is hoped this treatment will be better at shrinking tumors and with reduced side effects. The purpose of this study is to see how well the combination of Doxil, rituximab, cyclophosphamide, vincristine and prednisone (DR-COP) are in shrinking tumors in patients with non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Of Pegylated Liposomal Doxorubicin (Doxil) In Combination With Rituxan, Cyclophosphamide, Vincristine and Prednisone (DR-COP) In Newly Diagnosed Aggressive Non-Hodgkin's Lymphomas
• Actual Study Start Date: Jan 10, 2003
• Actual Primary Completion Date: Dec 19, 2012
• Actual Study Completion Date: May 7, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: DR-COP On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles.

Drug: Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone; Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1 Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles.

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Complete Response to the Combination Chemotherapy [At completion of cycle 4, 6, and 8]

   Initial disease response tests will be performed after cycle 4 on all patients. Subsequent assessments after cycles 6 and/or 8 will depend on response. If after 4 cycles of therapy complete response or partial response has been documented, therapy will continue. If stable or progressive disease has been documented, the patient will be withdrawn from the study. Response to the study treatment will be determined according to the criteria proposed in the "Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas" by Cheson et al (23).

Secondary Outcome Measures

1. Number of Patients With Serious Adverse Events as a Measure of Safety and Tolerability [At end of every cycle]

   Summary of grade 3 or higher toxicities (per Common Toxicity Criteria version 2.0) which generally is described as severe adverse reaction or symptom.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologic diagnosis of Non-Hodgkin's lymphoma of B-cell origin: follicular large cell, diffuse large cell (including all B-cell variants), Burkitt or Burkitt-like lymphoma

• All stages of disease

• Measurable or evaluable tumor parameter(s)

• Age greater than 17 years old

• Karnofsky performance status greater or equal to 50%

• AGC greater or equal to 1.0; platelets greater or equal to 75,000(unless abnormal because of lymphoma)

• Bilirubin less or equal to 2.0; SGOT less or equal to 3 times upper limit of normal (unless abnormal because of lymphoma)

• Creatinine less or equal to 2.0 or creatinine clearance greater or equal to 60 ml/min (unless abnormal because of lymphoma)

• LVEF greater or equal to 45%

• Concurrent RT with or without steroids for emergency conditions secondary to lymphoma (i.e., CNS tumor, cord compression)are permitted

• Men and women of childbearing potential must agree to use adequate birth control for the duration of the therapy and for 3 months after completion of therapy

• Signed informed consent

Exclusion Criteria:

• Prior systemic cytotoxic therapy or RT for lymphoma

• Second active tumor, other than non-melanomatous skin ca and in-situ cervical cancer

• HIV seropositive

• Primary CNS lymphoma

• Pregnant or nursing women

• Unable to comply with the requirements of the protocol, or unable to provide adequate informed consent, in the opinion of the PI

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033

Sponsors and Collaborators

• University of Southern California
• Ortho Biotech, Inc.

Investigators

• Principal Investigator: Anil Tulpule, MD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Southern California
• ClinicalTrials.gov Identifier: NCT00184002
• Other Study ID Numbers: 13NHL-02-3
• First Posted: Sep 16, 2005
• Last Update Posted: Aug 10, 2017
• Last Verified: Jul 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; Rituximab

Study Results

Participant Flow

Recruitment Details	The study began recruiting in January 2003 and ended in December 2007. All subjects were seen and treated either at USC Norris Comprehensive Cancer Center or at LAC+USC Medical Center.
Pre-assignment Detail	There were no pre-assignment criteria. All subjects were given the same treatment.

Arm/Group Title	DR-COP
Arm/Group Description	On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles. Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1
Period Title: Overall Study
STARTED	68
COMPLETED	51
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	DR-COP
Arm/Group Description	On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles. Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1
Overall Participants	68
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	60 88.2%
>=65 years	8 11.8%
Sex: Female, Male (Count of Participants)
Female	39 57.4%
Male	29 42.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	48 70.6%
Not Hispanic or Latino	20 29.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 17.6%
Native Hawaiian or Other Pacific Islander	1 1.5%
Black or African American	0 0%
White	7 10.3%
More than one race	0 0%
Unknown or Not Reported	48 70.6%
Region of Enrollment (participants) [Number]
United States	68 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Complete Response to the Combination Chemotherapy
Description	Initial disease response tests will be performed after cycle 4 on all patients. Subsequent assessments after cycles 6 and/or 8 will depend on response. If after 4 cycles of therapy complete response or partial response has been documented, therapy will continue. If stable or progressive disease has been documented, the patient will be withdrawn from the study. Response to the study treatment will be determined according to the criteria proposed in the "Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas" by Cheson et al (23).
Time Frame	At completion of cycle 4, 6, and 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DR-COP
Arm/Group Description	On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles. Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1
Measure Participants	68
Complete Response	75.0 110.3%
Partial Response	23.0 33.8%

2. Secondary Outcome

Title	Number of Patients With Serious Adverse Events as a Measure of Safety and Tolerability
Description	Summary of grade 3 or higher toxicities (per Common Toxicity Criteria version 2.0) which generally is described as severe adverse reaction or symptom.
Time Frame	At end of every cycle

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	DR-COP
Arm/Group Description	On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles. Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1
Measure Participants	68
Count of Participants [Participants]	35 51.5%

Adverse Events

Time Frame	Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose.
Arm/Group Title	DR-COP
Arm/Group Description	On cycle 1 patients receive Doxil 40 mg/m2 iv day 1 over a minimum of 60 min., Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min., Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5. On cycle 2 until study completion patients receive Doxil 40 mg/m2 iv day 1, Rituxan 375 mg/m2 iv day 1, Cyclophosphamide 750 mg/m2 iv day 1, Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum) and Prednisone 100 mg po days 1-5 1 cycle = 21 days. Continue treatment until 2 cycles beyond documentation of CR for a maximum of 8 cycles. Doxorubicin, Rituxan, Cyclophosphamide, Vincristine and Prednisone: Cycle 1 Doxil 40 mg/m2 iv day 1 over a minimum of 60 min. Cyclophosphamide 750 mg/m2 iv day 1 over a minimum of 60 min. Vincristine 1.4 mg/m2 iv bolus day 1 (2.0 mg maximum). Prednisone 100 mg po days 1-5. Cycle 2 until study completion Doxil 40 mg/m2 iv day 1 Rituxan 375 mg/m2 iv day 1 Cyclophosphamide 750 mg/m2 iv day 1
All Cause Mortality
	DR-COP
	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)
Serious Adverse Events
	DR-COP
	Affected / at Risk (%)	# Events
Total	35/68 (51.5%)
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)	35/68 (51.5%)	42
Hemoglobin	11/68 (16.2%)	13
Leukocytes (total WBC)	1/68 (1.5%)	2
Platelets	5/68 (7.4%)	9
Cardiac disorders
Cardiac left ventricular function	1/68 (1.5%)	1
Hypertension	2/68 (2.9%)	2
Hypotension	2/68 (2.9%)	2
Gastrointestinal disorders
Abdominal pain or cramping	2/68 (2.9%)	4
Diarrhea patients without colostomy	1/68 (1.5%)	1
Ileus (or neuroconstipation)	2/68 (2.9%)	2
Melena/GI bleeding	1/68 (1.5%)	1
Nausea	2/68 (2.9%)	2
Stomatitis/pharingitis (oral/pharyngeal mucositis)	2/68 (2.9%)	2
Vomiting	2/68 (2.9%)	2
General disorders
Fatigue (lethargy, malaise, asthenia)	1/68 (1.5%)	1
Weight loss	1/68 (1.5%)	1
Hepatobiliary disorders
Bilirubin	1/68 (1.5%)	1
SGOT (AST) (serum glutamic oxaloacetic transaminase)	3/68 (4.4%)	3
SGPT (ALT) (serum glutamic pyruvic transaminase)	3/68 (4.4%)	3
Infections and infestations
Febrile neutropenia	8/68 (11.8%)	8
Infection	8/68 (11.8%)	8
Infection without neutropenia	6/68 (8.8%)	6
Investigations
Cardiac troponin I (cTnl)	1/68 (1.5%)	1
Metabolism and nutrition disorders
Anorexia	1/68 (1.5%)	1
Dehydration	1/68 (1.5%)	1
Hyperglycemia	2/68 (2.9%)	5
Hypocalcemia	1/68 (1.5%)	1
Hypokalemia	3/68 (4.4%)	5
Hyponatremia	1/68 (1.5%)	1
Hypophosphatemia	1/68 (1.5%)	1
Tumor lysis syndrome	1/68 (1.5%)	1
Musculoskeletal and connective tissue disorders
Myalgia (muscle pain)	1/68 (1.5%)	1
Nervous system disorders
Neuropathy-sensory	2/68 (2.9%)	2
Renal and urinary disorders
Incontinence	1/68 (1.5%)	1
Ureteral obstruction	1/68 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	6/68 (8.8%)	6
Hypoxia	2/68 (2.9%)	2
Pleural effusion (non-malignant)	1/68 (1.5%)	1
Pneumonitis/pulmonary infiltrates	1/68 (1.5%)	2
Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis)	1/68 (1.5%)	1
Skin and subcutaneous tissue disorders
Hand-foot skin reaction	10/68 (14.7%)	10
Other (Not Including Serious) Adverse Events
	DR-COP
	Affected / at Risk (%)	# Events
Total	27/68 (39.7%)
Blood and lymphatic system disorders
Hemoglobin	23/68 (33.8%)	42
Leukocytes (total WBC)	1/68 (1.5%)	2
Neutrophils/granulocytes (ANC/AGC)	19/68 (27.9%)	34
Platelets	6/68 (8.8%)	14
Cardiac disorders
Cardiac left ventricular function	1/68 (1.5%)	1
Hypertension	5/68 (7.4%)	5
Hypotension	3/68 (4.4%)	3
Sinus bradycardia	3/68 (4.4%)	3
Sinus tachycardia	7/68 (10.3%)	10
Thrombosis/embolism	1/68 (1.5%)	1
Endocrine disorders
Hot flashes/flushes	2/68 (2.9%)	2
Eye disorders
Conjunctivitis	3/68 (4.4%)	3
Dry eye	1/68 (1.5%)	1
Vision-blurred vision	1/68 (1.5%)	1
Gastrointestinal disorders
Abdominal pain or cramping	12/68 (17.6%)	14
Ascites (non-malignant)	1/68 (1.5%)	1
Constipation	19/68 (27.9%)	25
Diarrhea patients without colostomy	12/68 (17.6%)	16
Dyspepsia/heartburn	7/68 (10.3%)	7
Dysphagia, esophagitis, odynophagia (painful swallowing)	5/68 (7.4%)	5
Flatulence	1/68 (1.5%)	1
Ileus (or neuroconstipation)	1/68 (1.5%)	1
Melena/GI bleeding	1/68 (1.5%)	1
Mouth dryness	1/68 (1.5%)	1
Nausea	22/68 (32.4%)	37
Sense of smell	2/68 (2.9%)	2
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	17/68 (25%)	24
Taste disturbance (dysgeusia)	14/68 (20.6%)	17
Vomiting	14/68 (20.6%)	22
General disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/68 (1.5%)	1
Chest pain (non-cardiac and non-pleuritic)	1/68 (1.5%)	1
Edema	11/68 (16.2%)	16
Fatigue (lethargy, malaise, asthenia)	22/68 (32.4%)	32
Fever	11/68 (16.2%)	12
Pain due to radiation	1/68 (1.5%)	1
Pain	27/68 (39.7%)	63
Rigors, chills	3/68 (4.4%)	3
Sweating (eiaphoresis)	2/68 (2.9%)	2
Weight loss	2/68 (2.9%)	2
Hepatobiliary disorders
Alkaline phosphatase	1/68 (1.5%)	1
Bilirubin	1/68 (1.5%)	1
Hypoalbuminemia	1/68 (1.5%)	1
SGOT (AST) (serum glutamic oxaloacetic transaminase)	5/68 (7.4%)	7
SGPT (ALT) (serum glutamic pyruvic transaminase)	5/68 (7.4%)	8
Infections and infestations
Infection without neutropenia	9/68 (13.2%)	15
Wound-infectious	1/68 (1.5%)	1
Injury, poisoning and procedural complications
Hemorrhage/bleeding	1/68 (1.5%)	1
Skin-Laate RT Morbidity Scoring	2/68 (2.9%)	2
Metabolism and nutrition disorders
Alkalosis (metabolic or respiratory)	1/68 (1.5%)	1
Anorexia	16/68 (23.5%)	19
Dehydration	1/68 (1.5%)	2
Hypercalcemia	1/68 (1.5%)	1
Hypercholesterolemia	2/68 (2.9%)	2
Hyperglycemia	15/68 (22.1%)	27
Hypermagnesemia	1/68 (1.5%)	1
Hypocalcemia	1/68 (1.5%)	1
Hypokalemia	6/68 (8.8%)	7
Hypomagnesemia	2/68 (2.9%)	2
Hypophosphatemia	1/68 (1.5%)	2
Musculoskeletal and connective tissue disorders
Arthralgia (joint pain)	5/68 (7.4%)	5
Bone pain	5/68 (7.4%)	11
Muscle weakness (not due to neuropathy)	4/68 (5.9%)	5
Myalgia (muscle pain)	2/68 (2.9%)	3
Nervous system disorders
Dizziness/lightheadedness	4/68 (5.9%)	4
Headache	14/68 (20.6%)	17
Neuropathy-motor	1/68 (1.5%)	1
Neuropathy-sensory	1/68 (1.5%)	1
Psychiatric disorders
Insomnia	15/68 (22.1%)	16
Mood alteration-anxiety, agitation	2/68 (2.9%)	2
Mood alteration-depression	3/68 (4.4%)	3
Renal and urinary disorders
Creatinine	1/68 (1.5%)	1
Dysuria (painful urination)	2/68 (2.9%)	2
Incontinence	1/68 (1.5%)	1
Urinary frequency/urgency	1/68 (1.5%)	1
Urinary retention	2/68 (2.9%)	2
Respiratory, thoracic and mediastinal disorders
Cough	8/68 (11.8%)	8
Dyspnea (shortness of breath)	9/68 (13.2%)	9
Hemoptysis	1/68 (1.5%)	1
Pleural Effusion (non-malignant)	1/68 (1.5%)	1
Pneumothorax	1/68 (1.5%)	1
Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis)	1/68 (1.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	24/68 (35.3%)	30
Hand-foot skin reaction	18/68 (26.5%)	23
Pigmentation changes (e.g., vitiligo)	2/68 (2.9%)	4
Pruritus	4/68 (5.9%)	4
Rash/desquamation	9/68 (13.2%)	10

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.