Sorafenib With or Without Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00114244
• Collaborator: (none)
• Enrollment: 52
• Location: 1
• Arms: 2
• Duration (Months): 69
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This randomized phase II is studying how well giving sorafenib with or without gemcitabine works in treating patients with metastatic pancreatic cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with gemcitabine may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Pancreatic Cancer	Drug: sorafenib tosylate; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the objective response rate in patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

SECONDARY OBJECTIVES:

1. To determine the six month overall survival rate, 3 month progression free survival rate, time to tumor progression and overall survival of patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

2. To determine the safety profile of gemcitabine and BAY43-9006 in patients with metastatic pancreatic cancer and compared to those treated with single agent BAY 43-9006.

3. To determine whether mRNA expression levels of genes involved in the gemcitabine pathway (RR, dck, dcd) and genes involved in the Raf pathway (cyclin D, VEGFR2, p21) will predict for time to progression, overall survival, and response, in patients with metastatic pancreatic cancer treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

4. To determine whether genomic polymorphisms of genes (measured in peripheral blood mononuclear cells) involved in the gemcitabine pathway (RR) and genes involved in the ras pathway (VEGFR2, cyclin D, p21) will predict for time to progression, overall survival, tumor response, and toxicity in patients with advanced cancer of the pancreas treated with concurrent gemcitabine and BAY43-9006 and sequential BAY 43-9006 followed by gemcitabine/BAY 43-9006 at progression.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.

ARM II: Patients receive oral sorafenib as in Arm I and gemcitabine IV over 100 minutes on days 1, 8, and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase II Study of BAY 43-9006 in Combination With Gemcitabine in Metastatic Pancreatic Carcinoma
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (sorafenib tosylate) Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II.	Drug: sorafenib tosylate; Given PO; Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Arm II (sorafenib tosylate, gemcitabine hydrochloride) Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15.	Drug: sorafenib tosylate; Given PO; Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN ; Drug: gemcitabine hydrochloride; Given IV; Other Names: dFdC difluorodeoxycytidine hydrochloride gemcitabine Gemzar ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Objective Response (OR = CR or PR) as Determined by the RECIST Criteria [Every 6 weeks.]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan, MRI, X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Secondary Outcome Measures

1. Overall Survival [From first day of treatment to time of death due to any cause, assessed up to 6 months]

   Estimated using the product-limit method of Kaplan and Meier by arm.

2. Progression-free Survival [From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 3 months]

   Estimated using the product-limit method of Kaplan and Meier by arm. The probability of progression-free survival at 3 months and overall survival at 6 months, and their Greenwood's standard errors will be summarized by arm.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic pancreatic carcinoma

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• No prior chemotherapy for metastatic disease is allowed; prior adjuvant chemotherapy is allowed provided that patients did not receive gemcitabine and the chemotherapy completed > 6 months prior to initiation of study therapy

• Available tumor biopsy specimen (paraffin embedded or fresh frozen) that was obtained at the time of diagnosis and/or prior to study entry is required

• Life expectancy of greater than 3 months

• ECOG performance status =< 1

• Leukocytes >= 3,000/μL

• Absolute neutrophil count >= 1,500/μL

• Platelets >= 100,000/μL

• Hemoglobin >= 9 mg/dL

• Total bilirubin =< 1.5 X institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) =< 3 X institutional upper limit of normal, unless the liver is involved with tumor, in which the AST (SGOT)/ALT (SGPT) must be =< 5 X institutional upper limit of normal

• Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2

• The effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because raf kinase inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Because BAY 43-9006 is at least partially metabolized by the CYP 3A enzyme in the liver, the possible effect that inhibitors of CYP 3A may have on BAY 43-9006 is unknown; therefore, patients taking inhibitors of CYP 3A (such as ketoconazole, itraconazole, and ritonavir) may not be enrolled in this study

• Patients may not be receiving any other investigational agents

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006 or gemcitabine

• Secondary primary malignancy (except in situ carcinoma of the cervix, in situ cancer of the prostate, in situ cancer of the breast or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence); concurrent or history of another malignancy =< 5 years

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the mother is treated with BAY 43-9006

• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

• Patients with evidence of bleeding diathesis

• Patients receiving therapeutic doses of anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Heinz-Josef Lenz, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00114244
• Other Study ID Numbers: NCI-2012-02835; NCI-2012-02835; PHII-50; 6576; N01CM62209
• First Posted: Jun 14, 2005
• Last Update Posted: Jan 14, 2015
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Arm I (Sorafenib Tosylate)	Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	15	37
COMPLETED	13	30
NOT COMPLETED	2	7

Baseline Characteristics

Arm/Group Title	Arm I (Sorafenib Tosylate)	Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)	Total
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	15	37	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66	65	65
Sex: Female, Male (Count of Participants)
Female	6 40%	15 40.5%	21 40.4%
Male	9 60%	22 59.5%	31 59.6%
Region of Enrollment (participants) [Number]
United States	15 100%	37 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response (OR = CR or PR) as Determined by the RECIST Criteria
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan, MRI, X-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame	Every 6 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Sorafenib Tosylate)	Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15	37
Number [participants]	0 0%	1 2.7%

2. Secondary Outcome

Title	Overall Survival
Description	Estimated using the product-limit method of Kaplan and Meier by arm.
Time Frame	From first day of treatment to time of death due to any cause, assessed up to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Sorafenib Tosylate)	Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15	37
Median (95% Confidence Interval) [Months]	4.3	6.5

3. Secondary Outcome

Title	Progression-free Survival
Description	Estimated using the product-limit method of Kaplan and Meier by arm. The probability of progression-free survival at 3 months and overall survival at 6 months, and their Greenwood's standard errors will be summarized by arm.
Time Frame	From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Sorafenib Tosylate)	Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies	Patients receive 400 mg oral sorafenib as in Arm I and 1000 mg/m2 gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15	37
Median (95% Confidence Interval) [Months]	2.3	2.9

Adverse Events

Time Frame	Adverse Events occured over a 36 month period.
Adverse Event Reporting Description	"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Arm/Group Title	Arm I (Sorafenib Tosylate)		Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
Arm/Group Description	Patients receive 400 mg oral sorafenib twice daily on days 1-28. Patients experiencing disease progression cross over to Arm II. sorafenib tosylate: Given PO laboratory biomarker analysis: Correlative studies		Patients receive 400 mg oral sorafenib as in Arm I and gemcitabine IV over 100 minutes on days 1, 8, and 15. sorafenib tosylate: Given PO gemcitabine hydrochloride: Given IV laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Arm I (Sorafenib Tosylate)		Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Sorafenib Tosylate)		Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/15 (53.3%)		15/37 (40.5%)
Cardiac disorders
Sinus tachycardia	1/15 (6.7%)	1	0/37 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	2	2/37 (5.4%)	2
Cheilitis	0/15 (0%)	0	1/37 (2.7%)	1
Constipation	1/15 (6.7%)	1	0/37 (0%)	0
Diarrhea	0/15 (0%)	0	1/37 (2.7%)	1
Duodenal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	2
Esophagitis	0/15 (0%)	0	1/37 (2.7%)	1
Gastritis	0/15 (0%)	0	1/37 (2.7%)	1
Gastrointestinal disorder	0/15 (0%)	0	1/37 (2.7%)	1
Intra-abdominal hemorrhage	1/15 (6.7%)	1	0/37 (0%)	0
Nausea	1/15 (6.7%)	2	2/37 (5.4%)	2
Obstruction gastric	0/15 (0%)	0	1/37 (2.7%)	1
Small intestinal obstruction	0/15 (0%)	0	1/37 (2.7%)	1
Upper gastrointestinal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Vomiting	1/15 (6.7%)	1	2/37 (5.4%)	2
General disorders
Death	0/15 (0%)	0	1/37 (2.7%)	1
Disease progression	2/15 (13.3%)	2	3/37 (8.1%)	3
Fatigue	0/15 (0%)	0	1/37 (2.7%)	1
Pain	1/15 (6.7%)	1	0/37 (0%)	0
Hepatobiliary disorders
Gallbladder obstruction	1/15 (6.7%)	1	0/37 (0%)	0
Infections and infestations
Catheter related infection	0/15 (0%)	0	1/37 (2.7%)	1
Skin infection	1/15 (6.7%)	1	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Vascular access complication	0/15 (0%)	0	3/37 (8.1%)	3
Investigations
Alkaline phosphatase increased	0/15 (0%)	0	1/37 (2.7%)	1
Hyperbilirubinemia	0/15 (0%)	0	1/37 (2.7%)	1
Metabolism and nutrition disorders
Dehydration	1/15 (6.7%)	1	2/37 (5.4%)	2
Hypocalcemia	0/15 (0%)	0	1/37 (2.7%)	1
Hyponatremia	0/15 (0%)	0	2/37 (5.4%)	2
Nervous system disorders
Ischemia cerebrovascular	1/15 (6.7%)	1	0/37 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	0/15 (0%)	0	1/37 (2.7%)	1
Vascular disorders
Thrombosis	4/15 (26.7%)	4	4/37 (10.8%)	4
Other (Not Including Serious) Adverse Events
	Arm I (Sorafenib Tosylate)		Arm II (Sorafenib Tosylate, Gemcitabine Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		37/37 (100%)
Blood and lymphatic system disorders
Blood disorder	0/15 (0%)	0	1/37 (2.7%)	1
Hemoglobin decreased	4/15 (26.7%)	13	17/37 (45.9%)	49
Thrombotic microangiopathy	0/15 (0%)	0	1/37 (2.7%)	1
Cardiac disorders
Sinus bradycardia	0/15 (0%)	0	1/37 (2.7%)	1
Sinus tachycardia	0/15 (0%)	0	1/37 (2.7%)	1
Ventricular flutter	0/15 (0%)	0	1/37 (2.7%)	1
Ear and labyrinth disorders
Ear disorder	0/15 (0%)	0	1/37 (2.7%)	1
Ear pain	0/15 (0%)	0	1/37 (2.7%)	2
Tinnitus	0/15 (0%)	0	1/37 (2.7%)	1
Eye disorders
Vision blurred	0/15 (0%)	0	2/37 (5.4%)	4
Gastrointestinal disorders
Abdominal distension	0/15 (0%)	0	3/37 (8.1%)	3
Abdominal pain	10/15 (66.7%)	17	21/37 (56.8%)	45
Ascites	0/15 (0%)	0	2/37 (5.4%)	3
Constipation	7/15 (46.7%)	9	14/37 (37.8%)	32
Diarrhea	5/15 (33.3%)	18	16/37 (43.2%)	36
Dyspepsia	0/15 (0%)	0	3/37 (8.1%)	4
Dysphagia	0/15 (0%)	0	1/37 (2.7%)	1
Ear, nose and throat examination abnormal	0/15 (0%)	0	5/37 (13.5%)	6
Esophageal mucositis	0/15 (0%)	0	1/37 (2.7%)	2
Esophagitis	0/15 (0%)	0	2/37 (5.4%)	3
Flatulence	0/15 (0%)	0	4/37 (10.8%)	6
Gastritis	1/15 (6.7%)	1	0/37 (0%)	0
Gastro-intestinal fistula	0/15 (0%)	0	1/37 (2.7%)	1
Hemorrhoids	0/15 (0%)	0	1/37 (2.7%)	1
Intra-abdominal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Lower gastrointestinal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Mucositis oral	0/15 (0%)	0	3/37 (8.1%)	5
Nausea	8/15 (53.3%)	13	14/37 (37.8%)	23
Oral pain	1/15 (6.7%)	2	0/37 (0%)	0
Rectal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Small intestinal obstruction	0/15 (0%)	0	1/37 (2.7%)	2
Stomach pain	0/15 (0%)	0	1/37 (2.7%)	1
Vomiting	5/15 (33.3%)	8	8/37 (21.6%)	10
General disorders
Chills	0/15 (0%)	0	7/37 (18.9%)	7
Death	1/15 (6.7%)	1	7/37 (18.9%)	7
Disease progression	11/15 (73.3%)	11	18/37 (48.6%)	18
Edema limbs	1/15 (6.7%)	1	4/37 (10.8%)	8
Fatigue	10/15 (66.7%)	33	27/37 (73%)	64
Fever	1/15 (6.7%)	1	4/37 (10.8%)	4
Flu-like symptoms	0/15 (0%)	0	1/37 (2.7%)	1
General symptom	1/15 (6.7%)	2	1/37 (2.7%)	1
Pain	0/15 (0%)	0	1/37 (2.7%)	2
Pericardial pain	1/15 (6.7%)	1	0/37 (0%)	0
Sudden death	0/15 (0%)	0	1/37 (2.7%)	1
Hepatobiliary disorders
Hepatic failure	0/15 (0%)	0	1/37 (2.7%)	1
Immune system disorders
Hypersensitivity	1/15 (6.7%)	1	0/37 (0%)	0
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)	0/15 (0%)	0	1/37 (2.7%)	1
Urinary tract infection	0/15 (0%)	0	1/37 (2.7%)	1
Wound infection	0/15 (0%)	0	1/37 (2.7%)	3
Injury, poisoning and procedural complications
Wound dehiscence	0/15 (0%)	0	3/37 (8.1%)	4
Investigations
Alanine aminotransferase increased	2/15 (13.3%)	3	19/37 (51.4%)	40
Alkaline phosphatase increased	5/15 (33.3%)	14	22/37 (59.5%)	41
Aspartate aminotransferase increased	2/15 (13.3%)	4	18/37 (48.6%)	43
Creatinine increased	0/15 (0%)	0	1/37 (2.7%)	2
Hyperbilirubinemia	2/15 (13.3%)	3	6/37 (16.2%)	7
Leukocyte count decreased	0/15 (0%)	0	3/37 (8.1%)	3
Leukopenia	1/15 (6.7%)	6	9/37 (24.3%)	18
Lymphocyte count decreased	0/15 (0%)	0	1/37 (2.7%)	1
Lymphopenia	1/15 (6.7%)	3	7/37 (18.9%)	13
Neutrophil count decreased	2/15 (13.3%)	6	17/37 (45.9%)	29
Platelet count decreased	3/15 (20%)	10	21/37 (56.8%)	54
Serum cholesterol increased	0/15 (0%)	0	1/37 (2.7%)	1
Weight loss	3/15 (20%)	5	10/37 (27%)	15
Metabolism and nutrition disorders
Anorexia	7/15 (46.7%)	17	21/37 (56.8%)	38
Blood bicarbonate decreased	0/15 (0%)	0	3/37 (8.1%)	3
Blood glucose increased	0/15 (0%)	0	3/37 (8.1%)	3
Dehydration	0/15 (0%)	0	3/37 (8.1%)	4
Glucose intolerance	0/15 (0%)	0	1/37 (2.7%)	2
Hypercalcemia	0/15 (0%)	0	3/37 (8.1%)	3
Hyperglycemia	2/15 (13.3%)	10	14/37 (37.8%)	29
Hyperkalemia	1/15 (6.7%)	1	0/37 (0%)	0
Hypermagnesemia	0/15 (0%)	0	2/37 (5.4%)	2
Hypernatremia	1/15 (6.7%)	1	2/37 (5.4%)	2
Hypoalbuminemia	1/15 (6.7%)	6	8/37 (21.6%)	19
Hypocalcemia	1/15 (6.7%)	5	9/37 (24.3%)	16
Hypoglycemia	1/15 (6.7%)	2	3/37 (8.1%)	3
Hypokalemia	2/15 (13.3%)	2	8/37 (21.6%)	16
Hypomagnesemia	0/15 (0%)	0	6/37 (16.2%)	8
Hyponatremia	0/15 (0%)	0	5/37 (13.5%)	7
Hypophosphatemia	1/15 (6.7%)	1	3/37 (8.1%)	7
Iron increased	0/15 (0%)	0	1/37 (2.7%)	1
Serum albumin decreased	0/15 (0%)	0	2/37 (5.4%)	2
Serum calcium decreased	0/15 (0%)	0	1/37 (2.7%)	1
Serum calcium increased	0/15 (0%)	0	1/37 (2.7%)	1
Serum glucose decreased	0/15 (0%)	0	1/37 (2.7%)	1
Serum phosphate decreased	0/15 (0%)	0	2/37 (5.4%)	2
Serum potassium decreased	0/15 (0%)	0	2/37 (5.4%)	2
Serum triglycerides increased	0/15 (0%)	0	1/37 (2.7%)	2
Musculoskeletal and connective tissue disorders
Back pain	3/15 (20%)	4	4/37 (10.8%)	5
Bone pain	0/15 (0%)	0	1/37 (2.7%)	1
Joint disorder	0/15 (0%)	0	2/37 (5.4%)	2
Joint effusion	0/15 (0%)	0	1/37 (2.7%)	2
Joint pain	0/15 (0%)	0	2/37 (5.4%)	2
Muscle weakness	2/15 (13.3%)	3	0/37 (0%)	0
Muscle weakness lower limb	0/15 (0%)	0	1/37 (2.7%)	1
Myalgia	1/15 (6.7%)	1	3/37 (8.1%)	3
Pain in extremity	0/15 (0%)	0	3/37 (8.1%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/15 (6.7%)	1	0/37 (0%)	0
Nervous system disorders
Depressed level of consciousness	2/15 (13.3%)	2	0/37 (0%)	0
Dizziness	0/15 (0%)	0	4/37 (10.8%)	6
Headache	0/15 (0%)	0	1/37 (2.7%)	1
Mental status changes	0/15 (0%)	0	1/37 (2.7%)	4
Neuralgia	0/15 (0%)	0	1/37 (2.7%)	1
Peripheral motor neuropathy	0/15 (0%)	0	5/37 (13.5%)	6
Peripheral sensory neuropathy	1/15 (6.7%)	1	2/37 (5.4%)	11
Speech disorder	1/15 (6.7%)	1	0/37 (0%)	0
Taste alteration	0/15 (0%)	0	2/37 (5.4%)	4
Psychiatric disorders
Anxiety	0/15 (0%)	0	1/37 (2.7%)	2
Insomnia	1/15 (6.7%)	1	7/37 (18.9%)	8
Personality change	0/15 (0%)	0	1/37 (2.7%)	1
Renal and urinary disorders
Bladder hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Hemorrhage urinary tract	0/15 (0%)	0	1/37 (2.7%)	1
Proteinuria	1/15 (6.7%)	1	3/37 (8.1%)	4
Urine discoloration	0/15 (0%)	0	1/37 (2.7%)	1
Reproductive system and breast disorders
Breast pain	0/15 (0%)	0	1/37 (2.7%)	1
Testicular pain	0/15 (0%)	0	1/37 (2.7%)	1
Vaginal hemorrhage	0/15 (0%)	0	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/15 (6.7%)	1	2/37 (5.4%)	4
Dyspnea	0/15 (0%)	0	1/37 (2.7%)	1
Hemorrhage nasal	0/15 (0%)	0	2/37 (5.4%)	3
Hiccough	0/15 (0%)	0	1/37 (2.7%)	1
Pharyngolaryngeal pain	0/15 (0%)	0	1/37 (2.7%)	1
Pneumonitis	0/15 (0%)	0	1/37 (2.7%)	1
Respiratory disorder	0/15 (0%)	0	2/37 (5.4%)	2
Voice alteration	0/15 (0%)	0	1/37 (2.7%)	1
Skin and subcutaneous tissue disorders
Acne	2/15 (13.3%)	2	2/37 (5.4%)	3
Alopecia	1/15 (6.7%)	2	10/37 (27%)	31
Dry skin	0/15 (0%)	0	1/37 (2.7%)	3
Erythema multiforme	0/15 (0%)	0	1/37 (2.7%)	1
Hand-and-foot syndrome	2/15 (13.3%)	2	5/37 (13.5%)	9
Pruritus	1/15 (6.7%)	1	1/37 (2.7%)	1
Rash desquamating	3/15 (20%)	3	9/37 (24.3%)	10
Skin disorder	0/15 (0%)	0	1/37 (2.7%)	1
Sweating	2/15 (13.3%)	4	2/37 (5.4%)	3
Vascular disorders
Hypertension	0/15 (0%)	0	2/37 (5.4%)	2
Phlebitis	0/15 (0%)	0	1/37 (2.7%)	1
Phlebitis superficial	1/15 (6.7%)	1	1/37 (2.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.