Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma

• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00826241
• Collaborator: CERN Foundation - Collaborative Ependymoma Research Network (Other)
• Enrollment: 58
• Locations: 6
• Arm: 1
• Actual Duration (Months): 114.9
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if lapatinib when given in combination with temozolomide can help to control ependymoma that has come back after treatment. The safety of this combination will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors; Spinal Cord Tumors	Drug: Temozolomide; Drug: Lapatinib	Phase 2

Detailed Description

The Study Drugs:

Temozolomide is designed to kill cancer cells by damaging deoxyribonucleic acid (DNA) (the genetic material of cells). This could cause the tumor cells to die.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the human epidermal growth factor receptor 2 (Her2/neu) receptor and the epidermal growth factor receptor (EGFR).

Study Drug Administration:

If you are found to be eligible to take part in this study, every day, you will take lapatinib by mouth once a day in the morning. You should take lapatinib 1 hour before or 1 hour after eating, with at least 1 cup (about 8 oz.) of water.

On Days 1-7 and 15-21 of each cycle, you will take temozolomide by mouth 1 time each day. You will start to take a lower dose of temozolomide for the first 2 cycles, then take a higher dose for Cycles 3 and beyond if you tolerate the treatment. It should be taken at least 2 hours before and 2 hours after eating with 1 cup (about 8 oz.) of water.

You should swallow temozolomide and/or lapatinib whole, one right after the other, without chewing either of the study drugs. If you vomit while taking temozolomide and lapatinib, you cannot take more capsules before the next scheduled dose. You should report any missed pills or trouble you have with taking the pills to your study doctor. Your study doctor will give you a form (patient diary) to fill out to keep track of your treatment. You will be asked to return your completed diary and pill bottles at each visit with your doctor.

Each study "cycle" is 28 days.

Study Visits:

Every 2 weeks, blood (about 2-3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot.

Every 8 weeks, the following tests and procedures will be performed:

• You will have a physical exam, including measurement of your vital signs.

• You will have a neurological exam.

• Your performance status will be recorded.

• You will be asked about any drugs you may be taking and if you have experienced any side effects.

• You will complete the quality of life questionnaire.

• You will have an magnetic resonance imaging (MRI) scan to check the status of the disease.

• You will have either a multi-gated acquisition scan (MUGA) scan (if the doctor thinks it is needed) or an echocardiogram.

Length of Study:

You will be on study treatment for up to 2 years. You will be taken off study treatment early if the disease gets worse or you experience intolerable side effects.

After you are off study, you may be able to continue taking lapatinib for as long as the doctor thinks it is in your best interest. Your doctor will discuss this with you.

End-of-Study Visit:

After you go off study treatment, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

• You will have a physical exam.

• Your performance status will be recorded.

• You will be asked about any drugs you may be taking and if you have experienced any side effects.

• You will have a neurological exam.

• Blood (about 3 teaspoons) will be drawn for routine tests and to check your blood's ability to clot.

• You will complete the questionnaire.

• You will have an MRI scan to check the status of the disease.

• You will have either a MUGA scan (if the doctor thinks it is needed) or an echocardiogram.

Long-Term Follow-up Visit:

If you go off treatment (having completed the maximum 24 months on study drug treatment) and have stable disease or response, you will have an MRI scan to check the status of the disease every 2 months for first year after you are off study, then every 3 months for the second year, then every 4 months for the third year, and then every 6 months from then on.

If you continue taking lapatinib after you have completed up to 24 months on study treatment, you will have a clinic visit and an MRI scan to check the status of the disease every 2 months for as long as the doctor thinks it is needed. At the clinic visits, you will be asked how you are doing.

If you went off study treatment because the disease got worse or you experienced intolerable side effects, after the end-of-study visit, the study staff will call you every 3 months from then on to check how you are doing. Each phone call will take about 5 minutes.

This is an investigational study. Temozolomide is Food and Drug Administration (FDA) approved or commercially available for the treatment of tumors of the nervous system. Lapatinib is FDA approved and commercially available for the treatment of breast cancer. However, lapatinib is not FDA approved for the treatment of brain tumors. The use of lapatinib with temozolomide in the treatment of brain tumors and spinal tumors is investigational.

Up to 50 patients will take part in this multicenter study. Up to 30 will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
• Actual Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jul 31, 2018
• Actual Study Completion Date: Jul 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Temozolomide + Lapatinib Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth.	Drug: Temozolomide; Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle.; Other Names: Temodar ; Drug: Lapatinib; Starting dose 1250 mg daily by mouth.; Other Names: GW572016

Outcome Measures

Primary Outcome Measures

1. Time to Progression [Assessed every two months till disease progression, up to 4 years]

   Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

Secondary Outcome Measures

1. Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria [4 weeks]

   Anti-tumor activity as determined by the overall response (Complete response (CR) or partial response (PR)) was assessed by the MacDonald criteria. Complete response is complete resolution of all lesions. The patient cannot be on any corticosteroids with the exception of adrenal replacement doses. Partial response is ≥50% reduction in the sum of products of all measurable lesions over baseline sum observed using the same techniques as baseline. The patient must be on a stable or decreased dose of corticosteroids to be evaluable for response.

2. Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) [Date treatment consent signed to date off study, approximately 111 months and 26 days]

   Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically proven ependymoma or anaplastic ependymoma. There must be pathologic or imaging confirmation of tumor progression or regrowth. The patients histologic diagnosis must be confirmed on Central Pathology Review prior to registration Step 2.

2. History and physical examination, including neurologic examination, within 2 weeks prior to registration.

3. Patients must be able to undergo brain or spine magnetic resonance imaging (MRI) scans with intravenous gadolinium, based on tumor location(s) within 14 days prior to registration.

4. Patients must be on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.

5. Karnofsky performance status >/= 70

6. Age >/= 18

7. Complete blood count (CBC)/differential obtained within 14 days prior to registration, with adequate bone marrow function defined as follows: 1) Absolute neutrophil count (ANC) >/= 1,500/mm^{3. 2) Platelets >/= 100,000 cells/mm}3. 3) Hemoglobin >/= 10.0 gm/dL (Note: The use of transfusion or other intervention to achieve Hgb >/= 10.0 is acceptable). 4) White blood cell count (WBC) >/= 3,000/mcL.

8. Adequate liver function within 14 days prior to registration, defined as follows: serum glutamic pyruvic transaminase (SGPT) [alanine aminotransferase (ALT)] < 2.5 times the upper limit of normal, Bilirubin </= 1.6 mg/dL

9. Adequate renal function within 14 days prior to registration, defined as follows: Creatinine < 1.7 mg/dL

10. Patients must have recovered from the toxic effects of prior therapy, and there must be a minimum time of: 1) 28 days from the administration of any investigational agent.

1. 28 days from administration of prior cytotoxic therapy with the following exceptions: (a) 14 days from administration of vincristine. (b) 42 days from administration of nitrosoureas. (c) 21 days from administration of procarbazine.

1. ( 11. continued) 3) 7 days from administration of non-cytotoxic agents [e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count)]. 4) 28 days from prior radiation therapy.

2. Patients must have recovered from the effects of surgery and a minimum of 14 days must have elapsed from the day of surgery to the day of registration. For core or needle biopsy, a minimum of 7 days must have elapsed prior to registration.

3. Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be done no later than 96 hours in the immediate postoperative period or at least 4 weeks postoperatively, within 14 days prior to registration. If the " within 96-hour of surgery " scan is more than 14 days before registration, the scan needs to be repeated.

4. Patients must sign study-specific informed consent and authorization for the release of their protected health information prior to registration. Patients must be registered in the MD Anderson Cancer Center Office of Multicenter Clinical Research (MDACC OMCR) database prior to treatment with study drug.

5. Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 14 days prior to registration.

6. Women of childbearing potential and male participants must practice adequate contraception

7. All patients must have an left ventricular ejection fraction (LVEF) measurement of at least 50% by Echo or MUGA (if clinically indicated) within 14 days prior to registration. The method used for LVEF assessment in an individual subject must be the same throughout the trial.

Exclusion Criteria:

1. Prior invasive malignancy that is not the ependymoma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years

2. Transmural myocardial infarction or unstable angina within 3 months prior to study registration

3. Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >/= 2 mm using the analysis of an electrocardiography (EKG) performed within 14 days prior to registration

4. New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration

5. History of stroke or transient ischemic attack within 3 months prior to registration.

6. Inadequately controlled hypertension (systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg despite antihypertensive medication)

7. History of cerebral vascular accident (CVA) within 3 months prior to registration

8. Serious and inadequately controlled cardiac arrhythmia

9. Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)

10. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

11. Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with acquired immunodeficiency syndrome (AIDS) from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.

12. Pregnant or nursing women because of concern of fetal/infant exposure to these agents

13. Any condition that impairs ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease).

14. Patients cannot be receiving enzyme-inducing anti-epileptic Drugs (EIAEDs) nor any other Image result for CYP3A4 Cytochrome P450 3A4 (CYP3A4) inducers such as rifampin or St. John's wort beginning at least 14 days prior to registration Step 2.

15. Patients cannot be receiving CYP3A4 inhibitors beginning at least 7 days prior to registration Step 2.

16. Patients must not have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).

17. Patients cannot be receiving HAART (Highly Active Anti-Retroviral Therapy) therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
5	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
6	University of Wisconsin School of Medicine and Public Health	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• National Institutes of Health Clinical Center (CC)
• CERN Foundation - Collaborative Ependymoma Research Network

Investigators

• Principal Investigator: Marta Penas-Prado, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 21, 2017
• Informed Consent Form - Jul 21, 2017

More Information

Additional Information:

• The University of Texas M.D.Anderson Cancer Center

Publications

None provided.

• Responsible Party: Mark Gilbert, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
• ClinicalTrials.gov Identifier: NCT00826241
• Other Study ID Numbers: 999916005; NCI-2012-02131; 16-C-N005
• First Posted: Jan 22, 2009
• Last Update Posted: Mar 22, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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
• Keywords provided by Mark Gilbert, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC): Brain Tumor; Central Nervous System; CNS; Spinal Cord Tumor; Anaplastic Ependymoma; Supratentorial Ependymoma; Infratentorial Ependymoma; Spinal Cord Ependymoma; Lapatinib; GW572016; Temozolomide; Temodar
• Additional relevant MeSH terms: Neoplasms; Brain Neoplasms; Ependymoma; Spinal Cord Neoplasms; Temozolomide; Lapatinib

Study Results

Participant Flow

Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Period Title: Overall Study
STARTED	58
COMPLETED	31
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Overall Participants	58
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	49 84.5%
>=65 years	9 15.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.77 (15.15)
Sex: Female, Male (Count of Participants)
Female	40 69%
Male	18 31%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	58 100%
American Indian/Alaskan Native	1 1.7%
Black	2 3.4%
White	51 87.9%
Unknown	3 5.2%
Other	1 1.7%
Region of Enrollment (Count of Participants)
United States	58 100%

Outcome Measures

1. Primary Outcome

Title	Time to Progression
Description	Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Time Frame	Assessed every two months till disease progression, up to 4 years

Outcome Measure Data

Analysis Population Description

8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Measure Participants	50
Median (95% Confidence Interval) [Months]	7.8

2. Secondary Outcome

Title	Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria
Description	Anti-tumor activity as determined by the overall response (Complete response (CR) or partial response (PR)) was assessed by the MacDonald criteria. Complete response is complete resolution of all lesions. The patient cannot be on any corticosteroids with the exception of adrenal replacement doses. Partial response is ≥50% reduction in the sum of products of all measurable lesions over baseline sum observed using the same techniques as baseline. The patient must be on a stable or decreased dose of corticosteroids to be evaluable for response.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Measure Participants	50
Complete Response	2 3.4%
Partial Response	8 13.8%

3. Secondary Outcome

Title	Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Description	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date treatment consent signed to date off study, approximately 111 months and 26 days

Outcome Measure Data

Analysis Population Description

8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Measure Participants	50
Count of Participants [Participants]	50 86.2%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 111 months and 26 days.
Adverse Event Reporting Description	8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Arm/Group Title	Temozolomide + Lapatinib
Arm/Group Description	Temozolomide starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m^2 daily by mouth on days 1-7 & 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
All Cause Mortality
	Temozolomide + Lapatinib
	Affected / at Risk (%)	# Events
Total	4/50 (8%)
Serious Adverse Events
	Temozolomide + Lapatinib
	Affected / at Risk (%)	# Events
Total	13/50 (26%)
Blood and lymphatic system disorders
Febrile neutropenia	1/50 (2%)	2
Gastrointestinal disorders
Diarrhea	1/50 (2%)	2
Hemorrhage, GU : Bladder	1/50 (2%)	2
Infections and infestations
Infection	2/50 (4%)	4
Infection with normal ANC or Grade 1 or 2 neutrophils : Skin (cellulitis)	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : Urinary tract NOS	1/50 (2%)	2
Investigations
Leukocytes (total WBC)	1/50 (2%)	2
Lymphopenia	2/50 (4%)	18
Neutrophils/granulocytes (ANC/AGC)	1/50 (2%)	2
Platelets	2/50 (4%)	4
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-lower	1/50 (2%)	2
Pain - Other (Specify, left hip)	1/50 (2%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment (Specify,B-cell/large cell lymphoma)	1/50 (2%)	2
Nervous system disorders
Ataxia (incoordination)	1/50 (2%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/50 (2%)	2
Pneumonitis/pulmonary infiltrates	1/50 (2%)	2
Pulmonary/Upper Respiratory - Other (Specify, __)	1/50 (2%)	2
Skin and subcutaneous tissue disorders
Pruritus/itching	1/50 (2%)	2
Surgical and medical procedures
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	1/50 (2%)	2
Vascular disorders
Thrombosis/thrombus/embolism	2/50 (4%)	4
Other (Not Including Serious) Adverse Events
	Temozolomide + Lapatinib
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Blood/Bone Marrow - Other (Specify, BUN)	1/50 (2%)	2
Blood/Bone Marrow - Other (Specify,elevated bilirubin)	1/50 (2%)	2
Leukocytes (total WBC)	30/50 (60%)	352
Lymphatics - Other (Specify, left thigh)	1/50 (2%)	2
Lymphatics - Other (Specify,mild peripheral edema)	1/50 (2%)	2
Cardiac disorders
Cardiac General - Other (Specify, sinus tachycardia)	1/50 (2%)	2
Palpitations	2/50 (4%)	4
Supraventricular and nodal arrhythmia : Atrial fibrillation	1/50 (2%)	2
Valvular heart disease	1/50 (2%)	4
Ear and labyrinth disorders
Auditory/Ear - Other (Specify, fluttering sensation)	1/50 (2%)	2
Auditory/Ear - Other (Specify, hearing loss; present at baseline)	1/50 (2%)	2
Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	2/50 (4%)	4
Hearing: patients without baseline audiogram and not enrolled in a monitoring program	2/50 (4%)	4
Tinnitus	4/50 (8%)	8
Endocrine disorders
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)	2/50 (4%)	4
Thyroid function, high (hyperthyroidism, thyrotoxicosis)	1/50 (2%)	2
Thyroid function, low (hypothyroidism)	2/50 (4%)	4
Eye disorders
Cataract	1/50 (2%)	2
Ocular/Visual - Other (Specify, Dysconjugate gaze. Present after surgery.)	1/50 (2%)	2
Ocular/Visual - Other (Specify, left hemaniopsia)	1/50 (2%)	2
Ocular/Visual - Other (Specify, vision loss left eye)	1/50 (2%)	2
Ocular/Visual - Other (Specify, visual impairment)	1/50 (2%)	2
Ophthalmoplegia/diplopia (double vision)	2/50 (4%)	4
Taste alteration (dysgeusia)	1/50 (2%)	2
Vision-blurred vision	7/50 (14%)	14
Vision-flashing lights/floaters	1/50 (2%)	2
Gastrointestinal disorders
Constipation	32/50 (64%)	82
Diarrhea	19/50 (38%)	46
Distension/bloating, abdominal	1/50 (2%)	4
Dysphagia (difficulty swallowing)	1/50 (2%)	2
Flatulence	1/50 (2%)	2
Gastritis (including bile reflux gastritis)	2/50 (4%)	4
Gastrointestinal - Other (Specify, abdominal distension)	1/50 (2%)	2
Gastrointestinal - Other (Specify, cramps in pelvis)	1/50 (2%)	2
Gastrointestinal - Other (Specify,gastrointestinal pain (intermittent))	1/50 (2%)	2
Gastrointestinal - Other (Specify, mucositis oral)	1/50 (2%)	2
Gastrointestinal - Other (Specify, rectal discomfort)	1/50 (2%)	2
Gastrointestinal - Other (Specify, stool incontinence)	1/50 (2%)	2
Heartburn/dyspepsia	2/50 (4%)	4
Hemorrhage, GI : Lower GI NOS	1/50 (2%)	2
Hemorrhage, GI : Oral cavity	1/50 (2%)	2
Hemorrhage, GI : Rectum	2/50 (4%)	4
Hemorrhage/Bleeding - Other (Specify, gums)	2/50 (4%)	4
Incontinence, anal	4/50 (8%)	8
Mucositis/stomatitis (clinical exam) :	1/50 (2%)	2
Mucositis/stomatitis (clinical exam) : Oral cavity	1/50 (2%)	2
Mucositis/stomatitis (functional/symptomatic) : Oral cavity	2/50 (4%)	4
Nausea	32/50 (64%)	82
Pain - Other (Specify, stomach pain)	1/50 (2%)	2
Pain : Abdomen NOS	1/50 (2%)	2
Pain : Oral cavity	1/50 (2%)	2
Vomiting	10/50 (20%)	24
General disorders
Constitutional Symptoms - Other (Specify, constipation)	1/50 (2%)	2
Constitutional Symptoms - Other (Specify, fatigue)	1/50 (2%)	2
Constitutional Symptoms - Other (Specify, hyposmia: reduced ability to smell)	1/50 (2%)	2
Constitutional Symptoms - Other (Specify,insomnia)	1/50 (2%)	2
Edema: head and neck	2/50 (4%)	4
Edema: limb	8/50 (16%)	18
Fatigue (asthenia, lethargy, malaise)	39/50 (78%)	102
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	4/50 (8%)	14
Pain	1/50 (2%)	2
Pain : Pain NOS	1/50 (2%)	2
Rigors/chills	2/50 (4%)	4
Syndromes - Other (Specify, tremors; left hand)	1/50 (2%)	2
Immune system disorders
Allergy/Immunology - Other (Specify, environmental allergic dry cough)	1/50 (2%)	2
Infections and infestations
Infection - Other (Specify, bronchial infection)	1/50 (2%)	2
Infection - Other (Specify,Other, toe fungal)	1/50 (2%)	2
Infection - Other (Specify,shingles)	3/50 (6%)	6
Infection - Other (Specify, Varicella Zoster)	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : Esophagus	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : External ear (otitis externa)	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : Skin (cellulitis)	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : Upper airway NOS	1/50 (2%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils : Urinary tract NOS	4/50 (8%)	10
Infection with unknown ANC : Bladder (urinary)	1/50 (2%)	2
Infection with unknown ANC : Urinary tract NOS	2/50 (4%)	4
Opportunistic infection associated with >=Grade 2 Lymphopenia	1/50 (2%)	2
Injury, poisoning and procedural complications
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	2/50 (4%)	4
Wound complication, non-infectious	1/50 (2%)	2
Investigations
Alkaline phosphatase	7/50 (14%)	18
ALT, SGPT (serum glutamic pyruvic transaminase)	17/50 (34%)	54
Amylase	1/50 (2%)	2
AST, SGOT(serum glutamic oxaloacetic transaminase)	16/50 (32%)	50
Bicarbonate, serum-low	1/50 (2%)	2
Bilirubin (hyperbilirubinemia)	4/50 (8%)	16
Cholesterol, serum-high (hypercholesteremia)	3/50 (6%)	6
Creatinine	6/50 (12%)	22
Hemoglobin	25/50 (50%)	190
Lipase	1/50 (2%)	2
Lymphopenia	35/50 (70%)	444
Neutrophils/granulocytes (ANC/AGC)	17/50 (34%)	154
Platelets	23/50 (46%)	174
Potassium, serum-high (hyperkalemia)	3/50 (6%)	6
Weight loss	9/50 (18%)	18
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)	6/50 (12%)	20
Anorexia	10/50 (20%)	22
Calcium, serum-low (hypocalcemia)	7/50 (14%)	20
Glucose, serum-high (hyperglycemia)	22/50 (44%)	86
Glucose, serum-low (hypoglycemia)	9/50 (18%)	24
Magnesium, serum-low (hypomagnesemia)	3/50 (6%)	8
Metabolic/Laboratory - Other (Specify, Akaline Phosphatase Serum Low)	2/50 (4%)	4
Metabolic/Laboratory - Other (Specify, Albumin serum high)	5/50 (10%)	10
Metabolic/Laboratory - Other (Specify,alkaline phosphatase count low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify,amylase serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify,AST-SGOT serum low)	3/50 (6%)	6
Metabolic/Laboratory - Other (Specify, BUN)	1/50 (2%)	6
Metabolic/Laboratory - Other (Specify, BUN count increased)	2/50 (4%)	6
Metabolic/Laboratory - Other (Specify, BUN serum high)	3/50 (6%)	12
Metabolic/Laboratory - Other (Specify, BUN serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, carbon dioxide)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, carbon dioxide count increased)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, carbon dioxide serum high)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, chloride count decreased)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, chloride serum high)	5/50 (10%)	12
Metabolic/Laboratory - Other (Specify, chloride serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, CO2 count increased)	2/50 (4%)	4
Metabolic/Laboratory - Other (Specify, CO2 high serum)	6/50 (12%)	18
Metabolic/Laboratory - Other (Specify, creatinine count decreased)	3/50 (6%)	6
Metabolic/Laboratory - Other (Specify, creatinine serum low)	7/50 (14%)	16
Metabolic/Laboratory - Other (Specify, hyperalbumin)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, hyperphosphatemia)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, LDH)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, LDH serum increased)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, LDH count decreased)	2/50 (4%)	4
Metabolic/Laboratory - Other (Specify, LDH count increased)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, LDH serum high)	3/50 (6%)	8
Metabolic/Laboratory - Other (Specify, LDH serum low)	2/50 (4%)	10
Metabolic/Laboratory - Other (Specify, phosphorous serum high)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, protein count decreased)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, protein serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, SGOT decreased count)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, total protein serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, uric acid serum low)	1/50 (2%)	2
Metabolic/Laboratory - Other (Specify, vitamin B12 deficiency)	1/50 (2%)	2
Phosphate, serum-low (hypophosphatemia)	4/50 (8%)	22
Potassium, serum-low (hypokalemia)	3/50 (6%)	12
Sodium, serum-high (hypernatremia)	5/50 (10%)	10
Sodium, serum-low (hyponatremia)	5/50 (10%)	18
Triglyceride, serum-high (hypertriglyceridemia)	2/50 (4%)	4
Uric acid, serum-high (hyperuricemia)	7/50 (14%)	26
Musculoskeletal and connective tissue disorders
Cervical spine-range of motion	1/50 (2%)	2
Extremity-lower (gait/walking)	18/50 (36%)	42
Muscle weakness, generalized or specific area (not due to neuropathy)	1/50 (2%)	4
Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-lower	7/50 (14%)	16
Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-upper	1/50 (2%)	2
Muscle weakness, generalized or specific area (not due to neuropathy) : Facial	1/50 (2%)	2
Muscle weakness, generalized or specific area (not due to neuropathy) : Left-sided	2/50 (4%)	4
Muscle weakness, generalized or specific area (not due to neuropathy) : Right-sided	5/50 (10%)	10
Muscle weakness, generalized or specific area (not due to neuropathy) : Whole body/generalized	3/50 (6%)	6
Musculoskeletal/Soft Tissue - Other (Specify, difficulty walking)	1/50 (2%)	2
Musculoskeletal/Soft Tissue - Other (Specify, intermittent back pain)	1/50 (2%)	2
Musculoskeletal/Soft Tissue - Other (Specify, left hand)	1/50 (2%)	2
Musculoskeletal/Soft Tissue - Other (Specify, lower extremity)	1/50 (2%)	2
Musculoskeletal/Soft Tissue - Other (Specify, paresthesia, left hand (carpal tunnel type syndrome)	1/50 (2%)	2
Musculoskeletal/Soft Tissue - Other (Specify, right back tightness)	1/50 (2%)	2
Pain - Other (Specify, back and right arm)	1/50 (2%)	2
Pain - Other (Specify, joint pain)	1/50 (2%)	2
Pain - Other (Specify, left anterior iliac spine)	1/50 (2%)	2
Pain - Other (Specify, left leg)	1/50 (2%)	2
Pain - Other (Specify, left sacrum pain)	1/50 (2%)	2
Pain - Other (Specify, leg pain)	1/50 (2%)	2
Pain - Other (Specify, musculoskeletal-back)	1/50 (2%)	2
Pain - Other (Specify, pain-pelvis)	1/50 (2%)	2
Pain - Other (Specify, RUQ)	1/50 (2%)	2
Pain - Other (Specify, severe pain left thigh)	1/50 (2%)	2
Pain : Back	13/50 (26%)	28
Pain : Bone	1/50 (2%)	2
Pain : Chest/thorax NOS	3/50 (6%)	6
Pain : Extremity-limb	4/50 (8%)	8
Pain : Joint	2/50 (4%)	4
Pain : Muscle	2/50 (4%)	4
Pain : Neck	1/50 (2%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain : Tumor pain	1/50 (2%)	2
Nervous system disorders
Ataxia (incoordination)	6/50 (12%)	14
Cognitive disturbance	4/50 (8%)	8
Dizziness	5/50 (10%)	10
Extrapyramidal/involuntary movement/restlessness	1/50 (2%)	2
Memory impairment	11/50 (22%)	22
Neurology - Other (Specify, __)	12/50 (24%)	32
Neuropathy: cranial : CN VII Motor-face; Sensory-taste	2/50 (4%)	4
Neuropathy: cranial : CN VIII Hearing and balance	1/50 (2%)	2
Neuropathy: motor	6/50 (12%)	12
Neuropathy: sensory	22/50 (44%)	52
Pain - Other (Specify, headaches)	1/50 (2%)	2
Pain - Other (Specify, neuralgia)	1/50 (2%)	2
Pain : Head/headache	17/50 (34%)	38
Pyramidal tract dysfunction	9/50 (18%)	18
Seizure	3/50 (6%)	8
Speech impairment (e.g., dysphasia or aphasia)	5/50 (10%)	10
Syncope (fainting)	2/50 (4%)	4
Psychiatric disorders
Confusion	2/50 (4%)	4
Insomnia	7/50 (14%)	14
Mood alteration :	1/50 (2%)	2
Mood alteration : Agitation	2/50 (4%)	4
Mood alteration : Anxiety	9/50 (18%)	18
Mood alteration : Depression	6/50 (12%)	14
Renal and urinary disorders
Incontinence, urinary	6/50 (12%)	14
Renal/Genitourinary - Other (Specify, urinary tract infection)	1/50 (2%)	4
Urinary frequency/urgency	7/50 (14%)	14
Urinary retention (including neurogenic bladder)	6/50 (12%)	12
Reproductive system and breast disorders
Erectile dysfunction	1/50 (2%)	2
Libido	1/50 (2%)	2
Obstruction, GU : Prostate	1/50 (2%)	2
Pain : Breast	1/50 (2%)	2
Vaginal dryness	1/50 (2%)	2
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	3/50 (6%)	6
Bronchospasm, wheezing	3/50 (6%)	6
Cough	9/50 (18%)	18
Dyspnea (shortness of breath)	10/50 (20%)	24
Hemorrhage/Bleeding - Other (Specify, nose)	1/50 (2%)	2
Nasal cavity/paranasal sinus reactions	3/50 (6%)	6
Pain : Throat/pharynx/larynx	1/50 (2%)	2
Pulmonary/Upper Respiratory - Other (Specify, sinus congestion)	1/50 (2%)	4
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	1/50 (2%)	2
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify, _)	1/50 (2%)	2
Dermatology/Skin - Other (Specify,steroid-related acne)	1/50 (2%)	2
Dermatology/Skin - Other (Specify, paresthesia)	1/50 (2%)	2
Dry skin	3/50 (6%)	6
Hair loss/alopecia (scalp or body)	4/50 (8%)	8
Nail changes	2/50 (4%)	4
Pain - Other (Specify, pain in the rash area chest and the back)	1/50 (2%)	2
Pruritus/itching	9/50 (18%)	22
Rash/desquamation	15/50 (30%)	48
Rash: acne/acneiform	16/50 (32%)	42
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	4/50 (8%)	8
Rash: hand-foot skin reaction	2/50 (4%)	4
Skin breakdown/decubitus ulcer	3/50 (6%)	6
Surgical and medical procedures
Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	1/50 (2%)	2
Vascular disorders
Flushing	1/50 (2%)	2
Hot flashes/flushes	2/50 (4%)	4
Hypertension	4/50 (8%)	8
Hypotension	1/50 (2%)	2
Thrombosis/embolism (vascular access-related)	1/50 (2%)	2
Thrombosis/thrombus/embolism	2/50 (4%)	4

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.