Clinical trial NCT01512186: A Phase II Study Investigating Upfront Pazopanib In Metastatic Renal Cancer Renal Cancer (Panther)
Official title: A Phase II Study Investigating Upfront Pazopanib In Metastatic Clear Cell Renal Cancer (Panther)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Metastatic Clear Cell Renal Cancer
Keywords: Clear cell renal cancer
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2012-01-19
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population for this trial are patients with confirmed clear cell carcinoma with measurable metastases on CT/MRI imaging (by RECIST). Only a component of clear cell is required.

Brief summary: The purpose of this study is to investigate if 14 weeks of pazopanib therapy prior to surgery (nephrectomy) is of benefit to patients with metastatic renal cancer. Ninety-five patients will be recruited into his study.

Detailed description: This is a Phase II, open label study evaluating pre-operative pazopanib treatment in previously untreated patients with metastatic clear cell renal cancer. This study follows a Simon 2 stage design

Patients will take pazopanib for 14 weeks followed by a nephrectomy. The drug will continue after nephrectomy until disease progression is documented. Patients will come off study once disease progression occurs, where they will then be followed for survival. Subsequent treatment at the discretion of the treating physician will be documented.

After surgery, all patients will be radiologically evaluated 8 weekly until progression. Standard radical nephrectomy with lymph node dissection will be performed on those patients who are deemed operable. The surgery can be laparoscopic or open. Those not deemed suitable for nephrectomy after 14 weeks of treatment will be offered a repeat biopsy.

Eligibility criteria: Inclusion Criteria:

* Histopathologically confirmed clear cell carcinoma with measurable metastases on CT/MRI imaging (by RECIST v1.1). Only a component of clear cell is required.

  * No prior systemic treatment or nephrectomy for RCC. Palliative radiotherapy is acceptable to non target lesions.
  * Adequate organ function as defined by the following criteria:

    i. Total serum bilirubin ≤1.5 x uln (patients with gilbert's disease exempt) ii. Serum transaminases (ALT) \<3 x uln iii. Calculated creatinine clearance \>30ml/min iv. Absolute neutrophil count (ANC) ≥1000/mm3 without growth factor support v. Platelets ≥ 75,000/mm3
  * Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
  * Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures
  * ECOG performance status of 0, 1 or 2.
  * 18 years or above (no upper age limit) Male or female

Exclusion Criteria:

* Congestive heart failure (class III or IV NYHA), myocardial infarction or coronary artery bypass graft/ stenting or stroke in the previous six months, ongoing severe or unstable arrhythmia requiring medication.

  * Previous treatment for renal cancer
  * Pregnancy or breastfeeding. Female patients must be surgically sterile, be postmenopausal, or must agree to use adequate contraception during the period of therapy.
  * Male patients must be surgically sterile or agree to use adequate contraception during the period of therapy.
  * Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would in the judgement of the investigator, impart excess risk associated with study participation or study drug administration, or which, in the judgement of the investigator, would make the patient inappropriate for entry into this study
  * Prolonged QT interval \>480msecs or a history of prolonged QT interval \>480msecs
  * Ongoing major gastrointestinal disease including ulcerative colitis, bleeding peptic ulcer disease or inflammatory bowel disease.
  * Bleeding diathesis
  * Current uncontrolled hypertension
  * Another malignancy requiring treatment within the last 5 years. Local prostate cancer not requiring hormone therapy or an asymptomatic raised PSA is acceptable.

Primary outcomes:
measure: Clinical benefit of 14 weeks of pre-operative pazopanib therapy, prior to nephrectomy using RECIST 1.1 criteria
timeFrame: Interim analysis after 34 patients have 12 weeks of treatment
Secondary outcomes:
measure: Surgical complications (blood loss, post operative complications, hospital stay)
timeFrame: After the first 20 patients have had a nephrectomy
measure: Overall Survival
timeFrame: After three years of study
measure: Progression free survival
timeFrame: After all patients have progresssed
measure: Local response of primary tumour to pazopanib
timeFrame: After 12 weeks of study drug
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon and Thurrock University Hospitals NHS Foundation Trust
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire NHS Trust
city: Glasgow
country: United Kingdom
facility: The Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Barts and London Hospital NHS Trust
city: London
country: United Kingdom
facility: Oncology & Clinical Haematology Trials Unit, Royal Free Hospital
city: London
country: United Kingdom
facility: Oncology & Haematology Clinical Trials Unit, Guy's Hospital
city: Oxford
country: United Kingdom
facility: Department of Oncology Oxford Cancer Centre
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Southend
country: United Kingdom
facility: Southend University Hospital Trust
Study officials:
References: