Renal cancer MedDRA version: 14.1 Level: PT Classification code 10038389 Term: Renal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Rapamune
Product Name: Rapamune
Pharmaceutical Form: Tablet
INN or Proposed INN: Rapamune
Other descriptive name: Rapamycin
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Localised or metastatic renal cell cancer, any histological subtype, suitable for repeat sampling. Prior histological proof is not required, but scan appearances of newly diagnosed patients should be consistent with localised or metastatic RCC. 2. Age >=18 years. 3. ECOG performance status 0-2 4. Life expectancy >3 months 5. Either: scheduled for biopsy and nephrectomy, or metastatic disease, suitable for 2 CT-guided biopsies, including accessible deposits >2cm in soft tissue or bone. 6. Untreated or previously treated with systemic therapy including multi-kinase inhibitor (eg sunitinib, sorafenib), immunotherapy (eg interferon) or experimental therapy. Radiotherapy is acceptable provided lesion chosen for biopsy is outside the irradiated field. 7. Able to give written informed consent and cooperate with protocol. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Clinical or CT scan features inconsistent with RCC unless pathologically confirmed. 2. Uncontrolled brain metastases. 3. Radiotherapy, major surgery, significant traumatic injury, systemic anti-cancer therapy (including immunotherapy, kinase inhibitor or experimental therapy) during the four weeks prior to starting study treatment. 4. Previous treatment with Rapamycin or Rapalogue (eg Everolimus, Temsirolimus). 5. Current or recent (within 10 days of Rapamycin) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes. Prophylactic use of anticoagulants is allowed. 6. History or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding. 7. Uncontrolled diabetes mellitus (HbA1c >8%). 8. Clinically significant (i.e. active) cardiovascular disease for example CVA (=6 months before enrolment), myocardial infarction (MI) (=6 months before enrolment) unstable angina, CHF NYHA Class =II study, cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted). 9. Non-healing wound, active peptic ulcer or bone fracture. 10. Known hypersensitivity to Rapamycin and any of its excipients. 11. Other psychological, social or medical condition, physical examination finding or laboratory abnormality that the Investigator considers would make the patient a poor study candidate, or could interfere with protocol compliance or the interpretation of results. 12. Co-administration of Rapamycin with strong inhibitors of CYP3A4 (such as ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampin, rifabutin). Low dose corticosteroids are permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Drugs that inhibit the mTOR enzyme have clinical activity in renal cancer, causing significant delay in disease progression, although with a low incidence of objective tumour regressions. This trial aims to identify early indicators of disease response or resistance. ; Secondary Objective: To determine the levels of Rapamycin or everolimus in the blood before and 2hr after dosing with Rapamycin tablets. Assess the safety profile of 2 weeks mTOR inhibitor treatment in this patient population Evaluate whether changes in pharmacodynamic readouts pre- and post anti-mTOR therapy are associated with clinical outcome at 12 months (Exploratory) To store samples of blood and tumour surplus to diagnostic and study requirements in the Oxford Radcliffe Biobank (ORB), for use in future ethically approved research. ; Primary end point(s): The pharmacodynamic effects of two weeks’ administration of mTOR inhibitor treatment on cell signaling and intratumoral blood flow. THese will be measured by: 1) Compare baseline and induced changes in phosphorylation of Akt and S6, and on proliferation by Ki67 index, measured by immunohistochemistry). 2) Assess changes in vascular volume and permeability by DCE MRI and perfusion CT imaging before and after Everolimus or Rapamycin. 3) Assess correlation between Everolimus/ Rapamycin-induced changes in IHC with changes in vascular volume and permeability. ;Timepoint(s) of evaluation of this end point: 14+-3 days following start of dosing with mTOR inibitor | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Determine circulating levels of Everolimus and Rapamycin 2) Assess the safety profile of 2 weeks mTOR inhibitor treatment in this patient population 3) Evaluate whether changes in pharmacodynamic readouts pre- and post anti-mTOR therapy are associated with clinical outcome at 12 months ; Timepoint(s) of evaluation of this end point: 1 & 2 will be assessed on or before the final study visit 4-6 weeks following second set of study scans and sample collection. 3) Progression free and overall survival will be evaluated at the aniversary of the final study biopsy. | — |
Countries
United Kingdom
Outcome results
None listed