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

NCT03334409 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACCRU-GU-1703NCI-2017-01998P30CA015083
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Treatment Failure-free Rate

  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.

  At 40 weeks

Secondary Outcomes (5)

• Overall Survival

  26 months

• Progression Free Survival

  16 Months

• Overall Response Rate

  16 Months

• Duration of Time on Pazopanib Hydrochloride

  10 months

• Frequency of Adverse Events

  10 Months

Study Arms (2)

Arm A (pazopanib hydrochloride, ascorbic acid)

EXPERIMENTAL

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; Drug: Pazopanib Hydrochloride

Arm B (pazopanib hydrochloride)

ACTIVE COMPARATOR

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

Interventions

Ascorbic Acid DRUG

Given IV

Also known as: 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

Arm A (pazopanib hydrochloride, ascorbic acid)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Arm A (pazopanib hydrochloride, ascorbic acid); Arm B (pazopanib hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (5)

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Sanford Medical Center Fargo

Fargo, North Dakota, 58104, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma

Interventions

Ascorbic Acid; pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Lance Pagliaro, M.D.
• Organization: Mayo Clinic, Rochester

Pagliaro.lance@mayo.edu

(507)293-0566

Study Officials

• Lance C Pagliaro

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 7, 2017
• Study Start: February 16, 2018
• Primary Completion: March 13, 2021
• Study Completion: March 13, 2021
• Last Updated: March 31, 2022
• Results First Posted: March 16, 2022

Record last verified: 2020-10

Locations

US (5)