A trial to examine the effect of pazopanib on survival in patients with metastatic renal cell cancer who have already received and relapsed on, or did not tolerate sunitinib treatment

Phase 1

• Conditions: Metastatic or unresectable renal cell carcinoma; MedDRA version: 16.0Level: PTClassification code 10067946Term: Renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022770-13-SE
• Lead Sponsor: ICORG- All Ireland Co-operative Oncology Research Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-02-27
• Last Update Posted: 16 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1) 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.
2) Age = 18 years
3) Diagnosis of metastatic/unresectable renal cell carcinoma of the clear cell type or with a component of clear cell histology
4) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
5) Measurable disease by RECIST criteria (Version 1.1) [28].
6) Eligible patients must have been treated with sunitinib for a minimum of 12 weeks (2 cycles). Patients must have evidence of progressive disease following treatment with sunitinib as assessed by the site investigator on the basis of CT scans and other appropriate clinical documentation. Patients who received sunitinib for a minimum of 12 weeks (2cycles) but stopped the drug due to toxicity rather than disease progression are also eligible for this study.
Patients who have had prior treatment with either temsirolimus or everolimus are also eligible for the trial.
No other prior treatment with bevacizumab, sorafenib, immunotherapies, chemotherapy, biologic therapy or investigational therapy is allowed.
Previous radiotherapy (RT) is permissible provided the measurable disease is outside the RT port. RT must be completed > 2 weeks prior to registration.
7) Adequate organ system function as defined below
Absolute neutrophil count (ANC) 1.5 X 109/L
Hemoglobin 9 g/dL (5.6 mmol/L)
Platelets 100 X 109/L
Prothrombin time (PT) or international normalized ratio (INR) 1.2 X ULN
Activated partial thromboplastin time (aPTT) 1.2 X ULN
Total bilirubin 1.5 X ULN
ALT and AST 2.5 X ULN
Serum creatinine 1.5 mg/dL (133 µmol/L) Or, if >1.5 mg/dL: Calculated creatinine clearance 50 mL/min
Urine Protein to Creatinine Ratio <1

8) 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 or urine 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. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
? Oral contraceptive, either combined or progestogen alone
? Injectable progestogen
? Implants of levonorgestre
? Estrogenic vaginal ring
? Percutaneous contraceptive patches
? 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

Exclusion Criteria

1) Prior malignancy.
2) History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases (surgery, radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible: a) are asymptomatic, b) have had no evidence of active CNS metastases for ?6 months prior to enrolment, and c) have no requirement for steroids or Enzyme -inducing anticonvulsants EIACs
3) 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, Chrohn’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.
4) Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:Malabsorption syndrome or Major resection of the stomach or small bowel.
5) Presence of uncontrolled infection.
6) Prolongation of corrected QT interval (QTc) > 480 msecs using Bazett’s formula.
7) History of any one or more of the following cardiovascular conditions within the past 6 months:Cardiac angioplasty or stenting, MI, Unstable angina, Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, NYHA Class III or IV congestive heart failure
8) Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =150 mmHg or diastolic blood pressure (DBP) of = 90mmHg].
9) History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
10) 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).
11) Evidence of active bleeding or bleeding diathesis.
12) Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
13) Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of study drug.
14) 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.
15) Unable or unwilling to discontinue use of prohibited medications list in Section 6.2.4 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
16) Treatment with any of the following anti-cancer therapies:
? Minor surgical procedure or tumor embolization within 14 days prior to the first dose of pazoapnib
? Previous radiotherapy (RT) is permissible provided the measurable disease is outside the RT port. RT must be completed > 2 weeks prior to registration.
? sunitinib, everolimus or temsirolimus within 14 days prior to the first dose of pazopanib
17) Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia. Note: Except where the toxicity is defined according to CTCAE v4.0 criteria as >Grade 1 due to the fact that the patient is taking medi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified