Pazopanib Hydrochloride Before Surgery in Treating Patients With Kidney Cancer

NCT01158521 | Completed Phase 2 Results DMC

• 2 other identifiers: CASE4809NCI-2010-01392
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pazopanib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well pazopanib hydrochloride works when given before surgery in treating patients with kidney cancer.

Conditions

Clear Cell Renal Cell Carcinoma; Stage I Renal Cell Cancer; Stage II Renal Cell Cancer; Stage III Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Could Undergo Partial Nephrectomy After Pazopanib Therapy

  The primary end point was the percentage of patients who could undergo partial nephrectomy after pazopanib therapy. A reduction in tumor size, with pazopanib treatment, may permit the use of a partial nephrectomy, as opposed to a radical nephrectomy. This would help preserve additional vascularized parenchyma.

  Partial nephrectomy performed after 8 to 16-weeks of pazopanib prescription. The median interval from treatment start to surgery was 10.6 weeks.

Secondary Outcomes (5)

• Residual Vascularized Parenchyma After Pazopanib Therapy and Subsequent Surgery Relative to Pre-therapy Assessment.

  After 8 to 16-weeks of pazopanib therapy and 7 day washout prior to surgery.

• Change in Tumor Diameter

  At the conclusion of 8 to 16-week treatment with pazopanib therapy.

• Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Target Lesions: Complete Response, Partial Response, Overall Response (OR)=CR+PR

  At the end of 8 to 16-weeks of treatment

• Surgical Morbidity

  post-surgery

• Reduction in Tumor Volume After Treatment

  After 8 to 16-weeks of pazopanib treatment

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.

Drug: pazopanib hydrochloride; Procedure: therapeutic conventional surgery

Interventions

pazopanib hydrochloride DRUG

Oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity.

Also known as: GW786034, Votrient

Arm I

therapeutic conventional surgery PROCEDURE

Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.

Arm I

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven renal carcinoma with a clear cell component
• Need for optimized partial nephrectomy based on one or more of the following criteria (all applicable criteria should be recorded and one criterion designated as the primary reason):
• Functional or anatomic solitary kidney, bilateral tumors, or pre-existing chronic kidney disease (CKD; estimated glomerular filtration rate (GFR) by Cockcroft-Gault formula \< 60 mL/min) and tumor amenable to partial nephrectomy, but partial nephrectomy would result in estimated GFR \< 30 mL/min; this estimation will be based on current estimated GFR, nuclear renal scan to estimate relative renal function (if 2 kidneys), tumor location(s), and amount of normal renal parenchyma that would need to be removed with nephrectomy
• Radical nephrectomy is required for tumor excision; however, it would result in estimated GFR \< 30 mL/min; this estimation will be based on current estimated GFR, nuclear renal scan to estimate relative renal function (if 2 kidneys), tumor location(s), and amount of normal renal parenchyma that would need to be removed with radical nephrectomy
• Greater than 30% likelihood that a partial nephrectomy would be associated with a high risk of significant morbidity (e.g. hemorrhage) due to proximity to the renal hilum (within 3 mm of main renal artery, renal vein or their primary branches) and/or other anatomic factors as determined by the operating surgeon
• Renal nephrometry score of 10-12
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Karnofsky \>= 70%
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2.5 x laboratory upper limit of normal (ULN)
• Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x laboratory upper limit of normal (ULN)
• Total serum bilirubin =\< 1.5 x ULN
• Absolute neutrophil count (ANC) \>= 1500/uL
• Platelets \>= 100,000/uL
• Hemoglobin \>= 9.0 g/dL (no transfusion permitted within 1 week)
• Serum creatinine =\< 2.5 mg/dL

You may not qualify if:

• Prior systemic treatment for RCC
• Evidence of any distant metastatic disease
• Evidence of bleeding diathesis or coagulopathy; patients with hematuria from the primary renal tumor are eligible provided all other eligibility criteria are met
• History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting; myocardial infarction; unstable angina; coronary artery bypass graft surgery; symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Prolongation of corrected QT interval (QTc) \> 480 msecs
• Hypertension that cannot be controlled by medications to \< 160/90 mmHg
• History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (Note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible)
• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
• Hemoptysis within 6 weeks of first dose of study drug
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
• Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
• Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease; known intraluminal metastatic lesion/s with suspected 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 within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome; major resection of the stomach or small bowel
• Prior major surgery or trauma (NOT including biopsy of renal mass; also procedures such as catheter placement not considered to be major) within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• Lane BR, Derweesh IH, Kim HL, O'Malley R, Klink J, Ercole CE, Palazzi KL, Thomas AA, Rini BI, Campbell SC. Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma. Urol Oncol. 2015 Mar;33(3):112.e15-21. doi: 10.1016/j.urolonc.2014.11.009. Epub 2014 Dec 19.

  PMID: 25532471 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

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

Limitations and Caveats

Requires further prospective study. Moreover, in this study, assessment of if partial nephrectomy is feasible prior to surgery was based on subjective measures. Outcome of subjects if they did not receive neoadjuvant therapy is unknown.

Results Point of Contact

• Title: Dr. Brian Rini
• Organization: Cleveland Clinic

rinib2@ccf.org

(216) 444-9567

Study Officials

• Brian Rini

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: July 1, 2010
• First Posted: July 8, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: September 12, 2018
• Results First Posted: September 12, 2018

Record last verified: 2018-08

Locations

US (2)