Pazopanib in Treating Patients With Metastatic Non-Clear Cell Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01767636
First received: January 10, 2013
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

This phase II trial studies how well pazopanib hydrochloride works in treating patients with metastatic kidney cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of kidney cancer by blocking blood flow to the tumor


Condition Intervention Phase
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Type 1 Papillary Renal Cell Carcinoma
Type 2 Papillary Renal Cell Carcinoma
Drug: pazopanib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Efficacy Trial of Pazopanib in Non-Clear Cell Metastatic Renal Cell Cancer (mRCC) PINCR

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Overall survival rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    A "12-month overall survivor" will be considered synonymous with "success". The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated.


Secondary Outcome Measures:
  • Tumor response rate, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    A tumor response is defined to be a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart.

  • Progression-free survival [ Time Frame: From registration to the earliest date documentation of disease progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curve will be used to estimate progression-free survival time.

  • Adverse event rate, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.


Estimated Enrollment: 39
Study Start Date: May 2013
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy of pazopanib (pazopanib hydrochloride) in non clear cell metastatic renal cell cancer patients as assessed by the overall survival rate at 12 months.

SECONDARY OBJECTIVES:

I. To determine the rates of best tumor response at the end of the first two treatment cycles of pazopanib in non clear cell metastatic renal cell cancer patients.

II. To determine the benefit of pazopanib in increasing progression free survival time.

III. To describe toxicity profile of pazopanib in non clear cell metastatic renal cell cancer patients.

OUTLINE:

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological confirmation of non-clear cell renal cancer (including chromophilic [papillary], chromophobic, oncocytic, sarcomatoid, collecting duct [Bellini's duct]) or medullary renal cell carcinoma
  • Up to one prior treatment for metastatic non clear cell carcinoma is allowed prior to registration as long as the agent used to treat was not pazopanib
  • Measurable or non-measurable metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1500
  • Platelets (PLT) >= 100,000
  • Hemoglobin (HgB) > 9.0 g/dL; NOTE: Subjects may not have had a transfusion within 7 days of registration)
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN; NOTE: Concomitant elevations in bilirubin and ALT/AST above 1.0 x ULN is not permitted
  • Urine protein to creatinine ratio (UPC) < 1; NOTE: If UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
  • Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 X ULN; NOTE: Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
  • Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula
  • 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 < 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 female who has had a negative serum pregnancy test, =< 7 days prior to registration
    • 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)
  • 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; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
  • Willing to return to Mayo Clinic enrolling institution for follow-up
  • Willing to provide, blood, tissue and urine samples for mandatory future unspecified correlative research purposes

Exclusion Criteria:

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

    • Nursing women
    • Pregnant women
    • Men or women 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 treatments
  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Symptomatic anemia, uncontrolled hypertension (defined as systolic blood pressure [SBP] of >= 140 mmHg or diastolic blood pressure [DBP] of >= 90mmHg)
    • Symptomatic congestive heart failure as defined by the New York Heart Association (NYHA); does not exclude class III congestive heart failure (CHF)
    • Previously treated with therapies that are known to negatively impact cardiac function (e.g. prior treatment with anthracyclines)
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Evidence of active bleeding or bleeding diathesis
    • Psychiatric illness/social situations that would limit compliance with study requirements
    • Or any other serious uncontrolled medical disorders in the opinion of the investigator
  • History of cerebrovascular accident including transient ischemic attack (TIA), myocardial infarction, pulmonary embolism or untreated deep venous thrombosis (DVT), coronary artery bypass graft surgery within 6 months prior to registration; Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating 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 registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; 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 first dose of study drug; 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 registration
    • 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
  • 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
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or hemoptysis in excess of 2.5 mL (or one half teaspoon) =< 8 weeks of registration
  • Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy =< 14 days prior to registration
  • 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 cytochrome P450 3A4 (CYP3A4); use of the strong or moderate inhibitors are prohibited =< 7 days prior to registration
  • Receiving any medications or substances that are inducers of CYP3A4; use of inducers are prohibited =< 7 days prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01767636

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Thai H Ho, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Brian A. Costello, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Brian A. Costello, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01767636     History of Changes
Other Study ID Numbers: MC1152, NCI-2012-02027
Study First Received: January 10, 2013
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014