Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01185366
• Collaborator: Novartis (Industry)
• Enrollment: 73
• Locations: 4
• Arms: 2
• Actual Duration (Months): 109.3
• Patients Per Site: 18.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to compare the effectiveness of Afinitor (everolimus) and Sutent (sunitinib) for the treatment of advanced renal cell carcinoma (kidney cancer). The safety of each treatment will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Drug: Everolimus; Drug: Sunitinib	Phase 2

Detailed Description

The Study Drugs:

Everolimus is designed to stop cells from multiplying. It may also stop the growth of new blood vessels that help tumor growth, which may cause the tumor cells to die.

Sunitinib is designed to block pathways that control important events (such as the growth of blood vessels) that are essential for the growth of cancer.

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups.

• If you are assigned to Group 1, you will take 2 everolimus tablets by mouth once every day.

• If you are assigned to Group 2, you will take sunitinib capsules by mouth every day for 4 weeks, followed by 2 weeks off.

If you have any side effects from any of the drugs, tell the study doctor right away. The study doctor may then lower the dose or keep the dose level the same.

Every 6 weeks on this study is called a study "cycle."

If the disease gets worse or you have intolerable side effects while you are on study, you will have the chance to receive the study drug that you did not receive at first. The dosing and follow-up will be the same as for all participants in that group.

Study Visits:

On Day 1 of every cycle:

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

• You will be asked about any drugs or treatments you may be receiving.

• Your performance status will be recorded.

• Blood (about 3 teaspoons) and urine will be collected for routine tests and a fasting blood sugar test. Blood or urine will also be used for a pregnancy test for women who are able to have children. If you are in Group 1, you will have an additional 1 teaspoon of blood drawn to test your cholesterol.

On Day 15 and 29 of Cycle 1:

• Your vital signs and weight will be measured.

• Blood (about 2 teaspoons) will be drawn for routine tests. If you are in Group 1, an additional 1 teaspoon of blood will be drawn to measure your cholesterol.

The Day 15 and Day 29 tests may be done at your local doctor's office.

On Day 1 of Cycles 2 and 3, and every other cycle after that (Day 1 of Cycle 5, 7, 9 and so on):

°You will have a CT scan of the chest and a CT scan or MRI of the abdomen to check the status of the disease.

Every 4 cycles (24 weeks):

°If you are in Group 2, you will have an echocardiogram or MUGA scan to check your heart's health.

Length of Study:

You may continue taking the study drugs for as long as you are benefiting. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Treatment Visit:

If you have stopped taking the study drug because of intolerable side effects, the treating physician will make every effort to check the status of the disease before you are taken off of study.

Long-Term Follow-up:

Once you are no longer on this study, the research staff will check up on you about every 6 months. This update will consist of a phone call or a review of your medical and/or other records. You will not have any extra tests, procedures, or study visits. If contacted by phone, the call would only last about 5 minutes.

This is an investigational study. Sunitinib and everolimus are both FDA approved and commercially available for the treatment of advanced kidney cancer.

Up to 108 patients will be enrolled in this multicenter trial. Up to 108 patients will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Everolimus Versus Sunitinib Therapy in Patients With Advanced Non-clear Cell Renal Cell Carcinoma
• Actual Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Sep 9, 2019
• Actual Study Completion Date: Sep 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Everolimus Group 1 Everolimus 10 mg by mouth once a day.	Drug: Everolimus; 10 mg by mouth once a day.; Other Names: Afinitor RAD001
Active Comparator: Sunitinib Group 2 Sunitinib 50 mg by mouth daily for 4 weeks on / 2 weeks off.	Drug: Sunitinib; 50 mg by mouth daily for 4 weeks on / 2 weeks off; Other Names: Sunitinib Malate SUO11248 Sutent

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) for First Line Medication [7 months]

   The amount of time after the first line medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.

2. Progression Free Survival (PFS) for Crossover Medication [4 months]

   The amount of time after the crossover medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.

Secondary Outcome Measures

1. Number of Participants Who Experienced Either a Grade 3 or 4 Adverse Event [1 year]

   Side effects, also called adverse events, that were related to either drug were documented and graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades increases in severity from 1 - 5. Grade one is a mild change which only requires monitoring. Grade 2 is a moderate change and may require some medication. Grade 3 is severe and requires hospitalization. Grade 4 is life threatening. Grade 5 is death.

2. Overall Survival of the First Line Therapy [17 months]

   The amount of time each participant is alive from the start of the first line therapy.

3. Number of Participants With Best Overall Response for First Line Medication [7 months]

   The best overall response for each participant was determined by using the Response Evaluation Criteria for Solid Tumors (RECIST). The responses are Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression Disease (PD). CR is the disappearance of the cancer everywhere in the participant. PR is at least a 30 % reduction in the measured tumors from baseline. SD is no discernible change in the presence of cancer. Progressive disease is an increase of at least 20% of the measured cancer from the cancer's smallest measure.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Patients must have advanced non-clear cell RCC, which may include but is not limited to the following subtypes: papillary I or II, chromophobe, collecting duct carcinoma (CDC), translocation or unclassified. Patients with conventional-type renal cell carcinoma who have >/= 20% sarcomatoid component in their primary tumor are eligible. Patients who have sarcomatoid features in FNA or core biopsy of any metastatic site are eligible, if they have an underlying renal cell carcinoma primary tumor.

2. Patients must have at least one measurable site of disease that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation

3. ECOG performance status 0-1

4. Age >/= 18 years

5. Patients must have adequate organ and marrow function within 14 days prior to study entry as defined below: a) Hemoglobin >/= 9 g/dl (tx allowed); b) absolute neutrophil count >/=1,500/microL; c) platelets >/= 100,000/microL; d) total bilirubin </= 1.5 mg/dl; e) AST(SGOT) or ALT (SGPT) </=2.5 X institutional uln, except in known hepatic metastasis, wherein may be </= 5 x ULN; f) Serum Creatinine </= 1.5 x ULN (as long as patient does not require dialysis)

6. INR and PTT </= 1.5 x ULN within 14 days prior to study entry. Therapeutic anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of warfarin or on a stable dose of LMW heparin for > 2 weeks (14 days) at time of randomization.

7. Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN within 14 days prior to study entry.

8. Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days before study entry. Pregnancy test must be repeated if performed > 14 days before starting study drug.

9. Patients must give written informed consent prior to study entry, in keeping with the policies of each institution.

10. Patients with a history of major psychiatric illness must be judged (by the treating physician) able to fully understand the investigational nature of the study and the risks associated with the therapy.

11. Patients with controlled brain metastases are allowed on protocol if they had solitary brain metastases that was surgically resected or treated with radiosurgery or Gamma knife, without recurrence or edema for 3 months (90days).

Exclusion Criteria:

1. No other malignancies within the past 2 years except for adequately treated carcinoma of the cervix or basal (without recurrence post-surgery or post-radiotherapy) or squamous cell carcinomas of the skin.

2. No prior systemic therapy for RCC including prior adjuvant therapy or investigational drug is allowed.

3. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks (28 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. However, patients are permitted to receive bisphosphonates. Also, patients who completed palliative radiation therapy prior to enrollment in this trial are eligible.

4. Patients, who have had a major surgery or significant traumatic injury (injury requiring > 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.

5. Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital) or CYP3A4 inhibitors is not recommended on this study.

6. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a) Symptomatic congestive heart failure of New York heart Association Class III or IV; b) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; c) severely impaired lung function as defined as 02 saturation that is 88% or less at rest on room air

7. (#6 cont'd) d) uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN;

1. active (acute or chronic) or uncontrolled severe infections requiring antibiotic intervention; f) liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

1. Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of sunitinib or everolimus or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

2. Concomitant treatment with drugs with dysrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, and indapamide) is not recommended.

3. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

4. Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period.

5. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.

6. A known history of HIV sero-positivity.

7. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus and/or sunitinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).

8. Patients with an active, bleeding diathesis.

9. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to study entry. Pregnancy test must be repeated if performed > 7 days before administration of everolimus and sunitinib)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute/Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
4	Huntsman Cancer Institute - University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Novartis

Investigators

• Principal Investigator: Amado Zurita, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 4, 2015

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01185366
• Other Study ID Numbers: 2009-0628; NCI-2012-01789
• First Posted: Aug 19, 2010
• Last Update Posted: Apr 28, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Advanced non-clear cell renal cell cancer (RCC); Clear-cell renal cell carcinoma; Collecting duct carcinoma; Translocation carcinoma; Chromophobe; Everolimus; Sunitinib; Afinitor; RAD001; Sunitinib Malate; SUO11248; Sutent; ESPN
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Everolimus; Sunitinib

Study Results

Participant Flow

Recruitment Details	73 Participants recruited from August 2010 to November 2013 at MD Anderson and Dana-Farber/Harvard Cancer Center.
Pre-assignment Detail	73 participants were recruited, 1 Screen failure. 69 participants were evaluable. Eligible patients did not take systemic medication for advanced papillary, chromophobe, CDC, Xp11.2 translocation, unclassified RCC or ccRCC with ≥ 20% sarcomatoid features in their primary tumors.

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Period Title: First Line Therapy
STARTED	38	34
Received 1st Drug	36	33
COMPLETED	35	33
NOT COMPLETED	3	1
Period Title: First Line Therapy
STARTED	35	33
Received Crossover Drug	21	23
COMPLETED	21	23
NOT COMPLETED	14	10

Baseline Characteristics

Arm/Group Title	Everolimus	Sunitinib	Total
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.	Total of all reporting groups
Overall Participants	35	33	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	60	60
Sex: Female, Male (Count of Participants)
Female	11 31.4%	14 42.4%	25 36.8%
Male	24 68.6%	19 57.6%	43 63.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 8.6%	5 15.2%	8 11.8%
Not Hispanic or Latino	3 8.6%	3 9.1%	6 8.8%
Unknown or Not Reported	29 82.9%	25 75.8%	54 79.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 5.7%	3 9.1%	5 7.4%
White	28 80%	25 75.8%	53 77.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	05 14.3%	5 15.2%	10 14.7%
Region of Enrollment (Count of Participants)
United States	35 100%	33 100%	68 100%
Histology (Count of Participants)
Papillary	13 37.1%	14 42.4%	27 39.7%
Clear Cell with sarcomatoid features	6 17.1%	6 18.2%	12 17.6%
Chromophobe	6 17.1%	6 18.2%	12 17.6%
Translocation	4 11.4%	3 9.1%	7 10.3%
Unclassified	6 17.1%	4 12.1%	10 14.7%
ECOG Performance Score (participants) [Number]
0	15 42.9%	18 54.5%	33 48.5%
1	20 57.1%	15 45.5%	35 51.5%
2	0 0%	0 0%	0 0%
3	0 0%	0 0%	0 0%
4	0 0%	0 0%	0 0%
5	0 0%	0 0%	0 0%
Memorial Sloan Kettering Risk Group (participants) [Number]
Good	4 11.4%	4 12.1%	8 11.8%
Intermediate	29 82.9%	29 87.9%	58 85.3%
Poor	2 5.7%	0 0%	2 2.9%
International Metastatic RCC Database Consortium Risk Score for Renal Cell Carcinoma (RCC) (participants) [Number]
Good	4 11.4%	3 9.1%	7 10.3%
Intermediate	24 68.6%	26 78.8%	50 73.5%
Poor	7 20%	4 12.1%	11 16.2%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) for First Line Medication
Description	The amount of time after the first line medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Measure Participants	35	33
Median (95% Confidence Interval) [months]	4.1	6.1

2. Primary Outcome

Title	Progression Free Survival (PFS) for Crossover Medication
Description	The amount of time after the crossover medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Measure Participants	21	23
Median (95% Confidence Interval) [months]	1.8	1.8

3. Secondary Outcome

Title	Number of Participants Who Experienced Either a Grade 3 or 4 Adverse Event
Description	Side effects, also called adverse events, that were related to either drug were documented and graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades increases in severity from 1 - 5. Grade one is a mild change which only requires monitoring. Grade 2 is a moderate change and may require some medication. Grade 3 is severe and requires hospitalization. Grade 4 is life threatening. Grade 5 is death.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression.
Measure Participants	57	51
Count of Participants [Participants]	18 51.4%	27 81.8%

4. Secondary Outcome

Title	Overall Survival of the First Line Therapy
Description	The amount of time each participant is alive from the start of the first line therapy.
Time Frame	17 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Measure Participants	35	33
Median (95% Confidence Interval) [months]	14.9	16.2

5. Secondary Outcome

Title	Number of Participants With Best Overall Response for First Line Medication
Description	The best overall response for each participant was determined by using the Response Evaluation Criteria for Solid Tumors (RECIST). The responses are Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression Disease (PD). CR is the disappearance of the cancer everywhere in the participant. PR is at least a 30 % reduction in the measured tumors from baseline. SD is no discernible change in the presence of cancer. Progressive disease is an increase of at least 20% of the measured cancer from the cancer's smallest measure.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Everolimus	Sunitinib
Arm/Group Description	4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Measure Participants	35	33
Complete Response	0 0%	0 0%
Partial Response	1 2.9%	3 9.1%
Stable Disease	26 74.3%	21 63.6%
Progressive Disease	8 22.9%	9 27.3%

Adverse Events

Time Frame	All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year.
Adverse Event Reporting Description	Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Arm/Group Title	Everolimus		Sunitinib
Arm/Group Description	4 weeks of everolimus 10 mg orally each day then 2 weeks of no medication until progression.		4 weeks of sunitinib 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
All Cause Mortality
	Everolimus		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/57 (36.8%)		20/51 (39.2%)
Serious Adverse Events
	Everolimus		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/57 (21.1%)		14/51 (27.5%)
Blood and lymphatic system disorders
CNS cerebrovascular ischemia	1/57 (1.8%)	1	0/51 (0%)	0
Hemorrhage	1/57 (1.8%)	1	3/51 (5.9%)	3
Gastrointestinal disorders
Vomiting	1/57 (1.8%)	1	0/51 (0%)	0
Diarrhea	1/57 (1.8%)	1	1/51 (2%)	1
Constipation	1/57 (1.8%)	1	0/51 (0%)	0
Immune system disorders
Platelets	0/57 (0%)	0	3/51 (5.9%)	3
Infections and infestations
Infection	2/57 (3.5%)	2	0/51 (0%)	0
Kidney Infection	1/57 (1.8%)	1	0/51 (0%)	0
Investigations
Hyponatremia	0/57 (0%)	0	2/51 (3.9%)	2
Musculoskeletal and connective tissue disorders
Muscle Weakness	0/57 (0%)	0	1/51 (2%)	1
Nervous system disorders
Pain	1/57 (1.8%)	1	2/51 (3.9%)	2
Renal and urinary disorders
Creatinine	0/57 (0%)	0	1/51 (2%)	1
Renal Failure	0/57 (0%)	0	1/51 (2%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/57 (8.8%)	5	0/51 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/57 (0%)	0	1/51 (2%)	1
Vascular disorders
Thrombosis	0/57 (0%)	0	1/51 (2%)	1
Other (Not Including Serious) Adverse Events
	Everolimus		Sunitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/57 (66.7%)		46/51 (90.2%)
Blood and lymphatic system disorders
Anemia	33/57 (57.9%)	88	33/51 (64.7%)	100
Hemorrhage	1/57 (1.8%)	1	7/51 (13.7%)	9
Leukocytes	12/57 (21.1%)	26	30/51 (58.8%)	112
Lymphopenia	3/57 (5.3%)	3	3/51 (5.9%)	9
Platelets	11/57 (19.3%)	21	32/51 (62.7%)	79
Endocrine disorders
Anorexia	9/57 (15.8%)	13	8/51 (15.7%)	9
Hypertension	2/57 (3.5%)	3	20/51 (39.2%)	33
Hypothyroidism	2/57 (3.5%)	2	3/51 (5.9%)	3
Hypothyroidism	2/57 (3.5%)	2	5/51 (9.8%)	6
Eye disorders
Watery eye	4/57 (7%)	6	2/51 (3.9%)	4
Watery eye	9/57 (15.8%)	13	6/51 (11.8%)	16
Gastrointestinal disorders
Constipation	9/57 (15.8%)	14	9/51 (17.6%)	10
Diarrhea	17/57 (29.8%)	33	26/51 (51%)	131
Mucositis	36/57 (63.2%)	111	27/51 (52.9%)	72
Nausea	17/57 (29.8%)	31	29/51 (56.9%)	115
Vomiting	6/57 (10.5%)	10	12/51 (23.5%)	44
Vomiting	11/57 (19.3%)	15	16/51 (31.4%)	50
General disorders
Hypoalbuminenia	3/57 (5.3%)	4	12/51 (23.5%)	23
AST	19/57 (33.3%)	33	23/51 (45.1%)	30
Fatigue	33/57 (57.9%)	96	46/51 (90.2%)	196
Dyspepsia	2/57 (3.5%)	4	13/51 (25.5%)	17
Pain	14/57 (24.6%)	31	21/51 (41.2%)	44
Hypertriglyderidemia	22/57 (38.6%)	45	0/51 (0%)	0
Hepatobiliary disorders
Hyperbilirubinemia	2/57 (3.5%)	6	7/51 (13.7%)	12
Infections and infestations
Infection	8/57 (14%)	9	4/51 (7.8%)	4
UTI	4/57 (7%)	5	3/51 (5.9%)	3
Metabolism and nutrition disorders
Alkaline phosphatase	5/57 (8.8%)	8	5/51 (9.8%)	6
ALT	12/57 (21.1%)	15	17/51 (33.3%)	21
Hypocalcemia	5/57 (8.8%)	6	13/51 (25.5%)	28
Hypercholestremia	27/57 (47.4%)	48	1/51 (2%)	1
Creatinine	20/57 (35.1%)	37	23/51 (45.1%)	50
Hyperglycemia	31/57 (54.4%)	74	17/51 (33.3%)	26
Hemoglobinuria	3/57 (5.3%)	3	2/51 (3.9%)	3
Hypophosphatemia	4/57 (7%)	6	6/51 (11.8%)	11
Hyperkalemia	2/57 (3.5%)	4	6/51 (11.8%)	8
Hypokalemia	1/57 (1.8%)	1	6/51 (11.8%)	11
Hyponatremia	3/57 (5.3%)	3	6/51 (11.8%)	18
Hypernatremia	5/57 (8.8%)		10/51 (19.6%)
Weight loss	5/57 (8.8%)	5	2/51 (3.9%)	3
Hyperkalemia	10/57 (17.5%)	11	8/51 (15.7%)	10
Hypokalemia	5/57 (8.8%)	16	10/51 (19.6%)	17
Hyponatremia	5/57 (8.8%)	10	3/51 (5.9%)	3
Hypernatremia	4/57 (7%)	4	11/51 (21.6%)	28
Hypertriglyceridemia	38/57 (66.7%)	78	2/51 (3.9%)	3
Weight loss	6/57 (10.5%)	6	2/51 (3.9%)	3
Magnesuim low	1/57 (1.8%)	1	3/51 (5.9%)	3
Hypernatremia	8/57 (14%)	13	0/51 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness	1/57 (1.8%)	1	5/51 (9.8%)	5
Neuropathy	3/57 (5.3%)	3	7/51 (13.7%)	9
Nervous system disorders
Depression	0/57 (0%)	0	3/51 (5.9%)	3
Neutrophils	3/57 (5.3%)	6	20/51 (39.2%)	79
Dysgeusia	6/57 (10.5%)	6	19/51 (37.3%)	20
Dysgeusia	10/57 (17.5%)	10	25/51 (49%)	27
Headache	4/57 (7%)	4	7/51 (13.7%)	12
Renal and urinary disorders
Proteinuria	15/57 (26.3%)	37	16/51 (31.4%)	27
Proteinuria	25/57 (43.9%)	47	22/51 (43.1%)	33
Respiratory, thoracic and mediastinal disorders
Cough	6/57 (10.5%)	9	3/51 (5.9%)	4
Dyspnea	19/57 (33.3%)	25	17/51 (33.3%)	34
Edema	12/57 (21.1%)	25	18/51 (35.3%)	38
Pneumonitis	6/57 (10.5%)	7	0/51 (0%)	0
Pneumonitis	10/57 (17.5%)	11	0/51 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	10/57 (17.5%)	10	8/51 (15.7%)	10
Nail changes	5/57 (8.8%)	5	3/51 (5.9%)	4
Rash	19/57 (33.3%)	52	24/51 (47.1%)	97
Rash	29/57 (50.9%)	64	21/51 (41.2%)	53
Hand foot skin reaction	1/57 (1.8%)	3	22/51 (43.1%)	70

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.