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Clear Cell Renal Cell CarcinomaPhase 2NCT01158521

Pazopanib Hydrochloride Before Surgery in Treating Patients With Kidney Cancer

A Phase 2 study testing pazopanib hydrochloride and therapeutic conventional surgery in people with Clear Cell Renal Cell Carcinoma and Stage I Renal Cell Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pazopanib hydrochloride and therapeutic conventional surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
Jun 2010to Jan 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Urine to protein to creatinine (UPC) ratio < 1; if UPC > 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1g to be eligible
  • Prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.2 X upper limit of normal (ULN)
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures; subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up
  • A female is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: a hysterectomy; a bilateral oophorectomy (ovariectomy); a bilateral tubal ligation; is post-menopausal
  • 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 < 40pg/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 female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; GlaxoSmithKlein (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: an intrauterine device with a documented failure rate of less than 1% per year; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female; 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; or double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide)

Who cannot join

  • 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
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  • 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
  • Presence of uncontrolled infection
  • Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: A Phase II Study of Pazopanib to Enable Partial Nephrectomy

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the rate of partial nephrectomy in patients with primary renal tumors otherwise requiring radical nephrectomy after neoadjuvant pazopanib treatment.

SECONDARY OBJECTIVES:

  1. To determine the safety, tumor diameter/volume change, conversion of hilar to non-hilar tumors and surgical morbidity of neoadjuvant pazopanib for renal cell carcinoma (RCC).

OUTLINE:

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.

After completion of study treatment, patients are followed up for 1 year.

Being tested
pazopanib hydrochloride, therapeutic conventional surgery
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pazopanib hydrochlorideDrug

    Also called GW786034, Votrient

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

  • therapeutic conventional surgeryProcedure or surgery

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

Study groups in NCT01158521
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: pazopanib hydrochloride; Procedure: therapeutic conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

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

    Measurement of total parenchymal tissue that could be saved with pazopanib therapy and subsequent surgery, which was performed via a volumetric analysis of CT images.

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

  2. Change in Tumor Diameter

    Median (cm) tumor size reduction after pazopanib treatment, relative to baseline (i.e., before treatment).

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

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

    Efficacy of pazopanib was evaluated via the Response Evaluation Criteria in Solid Tumors, version 1.1. Assessed by MRI. Definitions of response include Complete Response (CR), Disappearance of target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)=CR+PR

    Measured: At the end of 8 to 16-weeks of treatment

  4. Surgical Morbidity

    Conversion of tumor post therapy so that there is < 10% risk that a partial nephrectomy would be associated with a high risk of significant postoperative morbidity (e.g. conversion of tumor post therapy to ≥ 3 mm away from renal hilum (main renal artery, renal vein, or primary branches)

    Measured: post-surgery

  5. Reduction in Tumor Volume After Treatment

    Median (cm^3) tumor size reduction after pazopanib treatment, relative to baseline (i.e., before treatment).

    Measured: After 8 to 16-weeks of pazopanib treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01158521
Sponsor's protocol ID
CASE4809
Other IDs
NCI-2010-01392
Status last verified
Aug 2018
First submitted
1 Jul 2010
Last updated
12 Sep 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 25532471

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pazopanib hydrochloride and therapeutic conventional surgery in people with Clear Cell Renal Cell Carcinoma and Stage I Renal Cell Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Could Undergo Partial Nephrectomy After Pazopanib Therapy (time frame: Partial nephrectomy performed after 8 to 16-weeks of pazopanib prescription. The median interval from treatment start to surgery was 10.6 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01158521, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2018.

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