Pazopanib Hydrochloride With or Without Ascorbic Acid in Treating Patients With Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery

• Sponsor: Academic and Community Cancer Research United (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03334409
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Locations: 5
• Arms: 2
• Actual Duration (Months): 36.8
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well pazopanib hydrochloride with or without ascorbic acid work in treating patients with kidney cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ascorbic acid may help pazopanib hydrochloride stop tumor growth and improve treatment survival. Giving pazopanib hydrochloride and ascorbic acid may work better in treating patients with kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v7; Unresectable Renal Cell Carcinoma	Drug: Ascorbic Acid; Drug: Pazopanib Hydrochloride	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate and compare treatment failure-free rate at 40 weeks from randomization of patients with unresectable/metastatic clear cell renal cell carcinoma (ccRCC) receiving one of the following regimens: Arm A: pazopanib hydrochloride (pazopanib) 800 mg daily plus intravenous (IV) ascorbic acid 1g/kg 3 times/week and Arm B: pazopanib 800 mg daily.

SECONDARY OBJECTIVES:

1. To estimate and compare the overall survival (OS) in patients receiving pazopanib with or without IV ascorbic acid.

2. To estimate and compare the progression-free survival (PFS) in patients receiving pazopanib with or without IV ascorbic acid.

3. To estimate and compare the overall response rate (ORR) in patients receiving pazopanib with or without IV ascorbic acid.

4. To estimate and compare the duration on pazopanib treatment in patients receiving pazopanib with or without IV ascorbic acid.

5. To assess the adverse events (AE) profile and safety of each treatment arm using the Common Terminology Criteria for Adverse Events (CTCAE).

CORRELATIVE RESEARCH:

1. Correlation between 5 mC, 5 hmC and H3K27me3 expression (as determined by immunohistochemistry [IHC]), as well as MeDIP/hMeDIP sequencing (seq), and response to combination of IV ascorbic acid and pazopanib.

2. Correlation between iron content in tumor microenvironment (as determined by Prussian blue staining) and response to combination of IV ascorbic acid and pazopanib combination.

3. Correlation between HIF-1alpha and HIF-2alpha expression (as determined by immunohistochemistry [IHC]) and response to combination of IV ascorbic acid and pazopanib combination.

4. Correlation between GLUT1 expression (as determined by IHC) and response to combination of IV ascorbic acid and pazopanib.

5. Correlation between PDL1 expression (as determined by IHC) and response to combination of IV ascorbic acid and pazopanib.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Phase II Trial of Intravenous Ascorbic Acid (Vitamin C) as an Adjunct to Pazopanib in the First-Line or Post-Immunotherapy Setting for Metastatic or Unresectable Clear Cell Renal Cell Carcinoma (ccRCC)
• Actual Study Start Date: Feb 16, 2018
• Actual Primary Completion Date: Mar 13, 2021
• Actual Study Completion Date: Mar 13, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (pazopanib hydrochloride, ascorbic acid) Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Drug: Ascorbic Acid; Given IV; Other Names: 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one Asorbicap C Vitamin C-Long Ce-Vi-Sol Cecon Cenolate Cetane Cevalin L-Ascorbic Acid VIT C Vitamin C Vitamin-C ; Drug: Pazopanib Hydrochloride; Given PO; Other Names: GW786034B Votrient
Active Comparator: Arm B (pazopanib hydrochloride) Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Drug: Pazopanib Hydrochloride; Given PO; Other Names: GW786034B Votrient

Outcome Measures

Primary Outcome Measures

1. Treatment Failure-free Rate [At 40 weeks]

   Treatment failure is defined as any of the following: radiographic disease progression, off-protocol treatment due to adverse event, initiation of alternative therapy (except metastasectomy post clinical benefit (complete response [CR], partial response [PR], or stable disease [SD] per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 to treatment), and death due to any cause.

Secondary Outcome Measures

1. Overall Survival [26 months]

   Will be estimated using the method of Kaplan-Meier and be compared using log rank tests.

2. Progression Free Survival [16 Months]

   Will be estimated using the Kaplan-Meier method.

3. Overall Response Rate [16 Months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan, PET/CT, or MRI: Complete Response (CR), Disappearance of all target lesions and all target lymph nodes must have reduction in short axis to <1.0 cm; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation; Overall Response (OR) = CR + PR. Will be compared using a Chi-Square test.

4. Duration of Time on Pazopanib Hydrochloride [10 months]

   Will be described as the median time on treatment by arm.

5. Frequency of Adverse Events [10 Months]

   Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events and toxicities will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event frequencies for grade 3 or higher adverse events, will be compared using Chi-Square tests between the 2 treatment arms.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histological confirmation of clear cell renal cancer

• Documented metastatic or unresectable disease and at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; NOTE: Nephrectomy or ablation of the primary tumor is allowed prior to enrollment

• No prior systemic therapy for clear cell renal cancer or have progressed after immunotherapy such as ipilimumab plus nivolumab in the first line; other immunotherapies (e.g. interleukin-2) or additional lines of immunotherapy may be allowed after discussion with the principal investigator

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 21 days prior to registration)

• Platelet (PLT) >= 100,000/mm^3 (obtained =< 21 days prior to registration)

• Hemoglobin (Hgb) >= 9.0 g/dL (obtained =< 21 days prior to registration); NOTE: Subjects may not have had a transfusion =< 7 days of registration

• Total Bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 21 days prior to registration)

• NOTE: For bilirubin elevation 1 to 1.5 x ULN, alanine aminotransferase (ALT) above 1.5 x ULN (upper limit of normal) is not permitted

• NOTE: For bilirubin elevation 1 to 1.5 x ULN, aspartate aminotransferase (AST) above 1.5 x ULN (upper limit of normal) is not permitted

• Alanine amino transferase (ALT) < 2.5 X ULN, with normal bilirubin (obtained =< 21 days prior to registration); NOTE: Concomitant elevations in bilirubin and ALT above 1.5 x ULN (upper limit of normal) is not permitted

• Aspartate aminotransferase (AST) < 2.5 X ULN, with normal bilirubin (obtained =< 21 days prior to registration); NOTE: Concomitant elevations in bilirubin and AST above 1.5 x ULN (upper limit of normal) is not permitted

• Creatinine =< 1.5 mg/dl OR creatinine > 1.5 mg/dl, estimated creatinine clearance must be >= 55 mL/minute by Cockcroft Gault formula (obtained =< 21 days prior to registration)

• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained =< 21 days prior to registration); NOTE: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose

• Individuals of non-childbearing potential, or individual of childbearing potential with negative serum pregnancy test =< 7 days prior to randomization and willing to practice total abstinence or use a highly effective method of contraception, as outlined below:

• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female individual who has had the following:

• A hysterectomy

• A bilateral oophorectomy (ovariectomy)

• A bilateral tubal ligation

• Is post-menopausal

• NOTE: Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L); subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT

• Childbearing potential, including any individual who has had a negative serum pregnancy test, =< 7 days prior to randomization

• Agrees to use adequate contraception; acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows:

• Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product

• Oral contraceptive, either combined or progestogen alone

• Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year

• Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject

• Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

• Provide informed written consent

• Willing to provide archive tissue samples for correlative research purposes

Exclusion Criteria:

• Any of the following:

• Individuals/or persons who are nursing

• Individual/or persons who are pregnant

• Individuals/or persons of childbearing potential who are unwilling to employ adequate contraception

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive

• Prior history of receiving pazopanib or any other tyrosine kinase inhibitor treatments for malignancy

• Uncontrolled intercurrent illness including, but not limited to:

• Chronic ongoing or active infection

• Symptomatic anemia

• Uncontrolled hypertension (defined as systolic blood pressure [SBP] of >= 160 mmHg or diastolic blood pressure [DBP] of >= 100 mmHg)

• Symptomatic congestive heart failure as defined by the New York Heart Association (NYHA) (does not exclude class III congestive heart failure [CHF])

• Unstable angina pectoris

• Cardiac arrhythmia

• Evidence of active bleeding or bleeding diathesis

• Psychiatric illness/social situations that would limit compliance with study requirements

• Any other serious uncontrolled medical disorders in the opinion of the investigator

• History of a major thromboembolic event =< 6 months prior to randomization, including cerebrovascular accident, transient ischemic attack (TIA), myocardial infarction, symptomatic pulmonary embolism (PE) or untreated deep venous thrombosis (DVT), or coronary artery bypass graft surgery; NOTE: Subjects with recent DVT or asymptomatic PE who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible

• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm

• Other active malignancy =< 5 years prior to randomization; EXCEPTIONS: Nonmelanoma skin cancer or carcinoma-in-situ of the cervix, or cancers with low metastatic potential (e.g. Gleason score 6 prostate cancer) treated with curative therapy; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer

• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for =< 6 months prior to randomization; Note: Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases

• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

• Active peptic ulcer disease

• Known intraluminal metastatic lesion/s with risk of bleeding

• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn?s disease), or other gastrointestinal conditions with increased risk of perforation

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 28 days prior to randomization

• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

• Malabsorption syndrome

• Any prior major resection of the stomach or small bowel

• Corrected QT interval (QTc) > 480 msecs using Bazett?s formula

• Receiving any medications or substances with risk of Torsades de Pointes; Note: medications or substances on the list ?Drugs with Risk of Torsades de Pointes? are prohibited; medications or substances on the list ?Drugs with Possible or Conditional Risk of Torsades de Pointes? may be used while on study with extreme caution and careful monitoring

• Treatment with any of the following anti-cancer therapies =< 14 days prior to registration:

• Radiation therapy

• Surgery or tumor embolization

• Chemotherapy, immunotherapy

• Biologic therapy

• Investigational therapy

• Hormonal therapy

• Prior autologous or allogeneic organ or tissue transplantation

• Elective or planned major surgery to be performed during the course of the trial

• Receiving any medications or substances that are strong or moderate inhibitors of CYP3A4; use of strong or moderate inhibitors are prohibited =< 7 days prior to randomization

• Receiving any medications or substances that are inducers of CYP3A4; use of inducers are prohibited =< 7 days prior to randomization

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency (i.e. below normal limits)

• End-stage renal disease (estimated glomerular filtration rate [GFR] < 55 ml/min/body surface area [BSA]), unless the estimated creatinine clearance by Cockcroft Gault is

= 55 ml/min prior to randomization

• History of calcium oxalate stones

• History of iron overload

• Unable to swallow oral medications

• History of myocardial infarction =< 6 months, current symptomatic CHF or left ventricular ejection fraction (LVEF) < 40% or > grade 2 diastolic dysfunction, with no symptoms or signs of heart failure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
2	Carle Cancer Center	Urbana	Illinois	United States	61801
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
5	Sanford Medical Center Fargo	Fargo	North Dakota	United States	58104

Sponsors and Collaborators

• Academic and Community Cancer Research United
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Lance C Pagliaro, Academic and Community Cancer Research United

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 28, 2019

More Information

Publications

None provided.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT03334409
• Other Study ID Numbers: ACCRU-GU-1703; NCI-2017-01998; ACCRU-GU-1703; P30CA015083
• First Posted: Nov 7, 2017
• Last Update Posted: Mar 31, 2022
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Vitamins; Ascorbic Acid

Study Results

Participant Flow

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	2	3
COMPLETED	1	3
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)	Total
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	1	3	4
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55	56.7	56.3
Sex: Female, Male (Count of Participants)
Female	0 0%	1 33.3%	1 25%
Male	1 100%	2 66.7%	3 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	3 100%	4 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
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	0 0%	0 0%	0 0%
White	1 100%	3 100%	4 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
MSKCC Risk Factor (Count of Participants)
Poor risk	1 100%	1 33.3%	2 50%
Intermediate risk	0 0%	1 33.3%	1 25%
Favorable risk	0 0%	1 33.3%	1 25%

Outcome Measures

1. Primary Outcome

Title	Treatment Failure-free Rate
Description	Treatment failure is defined as any of the following: radiographic disease progression, off-protocol treatment due to adverse event, initiation of alternative therapy (except metastasectomy post clinical benefit (complete response [CR], partial response [PR], or stable disease [SD] per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 to treatment), and death due to any cause.
Time Frame	At 40 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Count of Participants [Participants]	0 0%	2 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Overall Survival
Description	Will be estimated using the method of Kaplan-Meier and be compared using log rank tests.
Time Frame	26 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Median (Full Range) [Months]	7.8	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Progression Free Survival
Description	Will be estimated using the Kaplan-Meier method.
Time Frame	16 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Median (Full Range) [Months]	5.7	11.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Overall Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan, PET/CT, or MRI: Complete Response (CR), Disappearance of all target lesions and all target lymph nodes must have reduction in short axis to <1.0 cm; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation; Overall Response (OR) = CR + PR. Will be compared using a Chi-Square test.
Time Frame	16 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Count of Participants [Participants]	0 0%	1 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Duration of Time on Pazopanib Hydrochloride
Description	Will be described as the median time on treatment by arm.
Time Frame	10 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Median (Full Range) [Months]	5.9	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Kruskal-Wallis
	Comments

6. Secondary Outcome

Title	Frequency of Adverse Events
Description	Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events and toxicities will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event frequencies for grade 3 or higher adverse events, will be compared using Chi-Square tests between the 2 treatment arms.
Time Frame	10 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)	Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.	Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Measure Participants	1	3
Count of Participants [Participants]	1 100%	2 66.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Pazopanib Hydrochloride, Ascorbic Acid), Arm B (Pazopanib Hydrochloride)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed up to 10 months. All-Cause Mortality assessed up to 26 months
Arm/Group Title	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)		Arm B (Pazopanib Hydrochloride)
Arm/Group Description	Patients receive pazopanib hydrochloride PO QD on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.		Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)		Arm B (Pazopanib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/3 (0%)
Serious Adverse Events
	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)		Arm B (Pazopanib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/3 (33.3%)
Infections and infestations
Lung infection	1/1 (100%)	1	0/3 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/1 (100%)	1	0/3 (0%)	0
Investigations
Alanine aminotransferase increased	0/1 (0%)	0	1/3 (33.3%)	2
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/1 (100%)	1	0/3 (0%)	0
Vascular disorders
Thromboembolic event	1/1 (100%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A (Pazopanib Hydrochloride, Ascorbic Acid)		Arm B (Pazopanib Hydrochloride)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anemia	0/1 (0%)	0	1/3 (33.3%)	1
Endocrine disorders
Hypothyroidism	0/1 (0%)	0	1/3 (33.3%)	1
Eye disorders
Dry eye	0/1 (0%)	0	1/3 (33.3%)	1
Eye disorders - Other, specify	0/1 (0%)	0	1/3 (33.3%)	1
Gastrointestinal disorders
Anal fistula	0/1 (0%)	0	1/3 (33.3%)	1
Diarrhea	1/1 (100%)	2	3/3 (100%)	19
Dry mouth	0/1 (0%)	0	1/3 (33.3%)	3
Dyspepsia	0/1 (0%)	0	1/3 (33.3%)	1
Dysphagia	0/1 (0%)	0	1/3 (33.3%)	2
Flatulence	0/1 (0%)	0	1/3 (33.3%)	1
Mucositis oral	0/1 (0%)	0	2/3 (66.7%)	3
Nausea	1/1 (100%)	4	3/3 (100%)	15
General disorders
Fatigue	1/1 (100%)	6	3/3 (100%)	26
Gen disord and admin site conds-Oth spec	0/1 (0%)	0	1/3 (33.3%)	3
Pain	0/1 (0%)	0	1/3 (33.3%)	4
Infections and infestations
Urinary tract infection	0/1 (0%)	0	1/3 (33.3%)	1
Investigations
Alanine aminotransferase increased	0/1 (0%)	0	2/3 (66.7%)	5
Aspartate aminotransferase increased	0/1 (0%)	0	2/3 (66.7%)	5
Blood bilirubin increased	0/1 (0%)	0	1/3 (33.3%)	2
Creatinine increased	0/1 (0%)	0	2/3 (66.7%)	15
GGT increased	0/1 (0%)	0	1/3 (33.3%)	2
Weight loss	0/1 (0%)	0	1/3 (33.3%)	8
Metabolism and nutrition disorders
Dehydration	0/1 (0%)	0	1/3 (33.3%)	1
Hypoglycemia	0/1 (0%)	0	1/3 (33.3%)	1
Hyponatremia	0/1 (0%)	0	1/3 (33.3%)	2
Musculoskeletal and connective tissue disorders
Myalgia	0/1 (0%)	0	1/3 (33.3%)	2
Nervous system disorders
Dysgeusia	0/1 (0%)	0	1/3 (33.3%)	8
Headache	0/1 (0%)	0	1/3 (33.3%)	1
Nervous system disorders - Oth spec	0/1 (0%)	0	1/3 (33.3%)	1
Peripheral sensory neuropathy	1/1 (100%)	5	1/3 (33.3%)	3
Psychiatric disorders
Anxiety	0/1 (0%)	0	1/3 (33.3%)	2
Depression	0/1 (0%)	0	1/3 (33.3%)	2
Reproductive system and breast disorders
Vaginal dryness	0/1 (0%)	0	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/1 (0%)	0	1/3 (33.3%)	2
Epistaxis	0/1 (0%)	0	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrm	0/1 (0%)	0	1/3 (33.3%)	4
Skin and subcut tissue disord - Oth spec	0/1 (0%)	0	1/3 (33.3%)	2
Social circumstances
Social circumstances - Other, specify	0/1 (0%)	0	1/3 (33.3%)	1
Vascular disorders
Hypertension	1/1 (100%)	4	3/3 (100%)	24

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.