| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| To investigate the effect of an anti-inflammatory therapy consisting of pioglitazone (Actos) in combination with an angiostatic treatment with sorafenib (Nexavar) and Interferin-Alpha (Roferon) on progression-free survival (PFS) in metastatic, non resectable renal clear cell carcinoma (RCCC) |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10038416 |
| E.1.2 | Term | Renal clear cell carcinoma |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Phase I: To determine the dose of pioglitazone to be used in phase II and to obtain pharmacokinetic data about sorafenib and pioglitazone for the investigated treatment regimen
Phase II: to determine progression-free survival
• Progression-free survival (primary objective) is defined as the time interval between the date of study entry and the date of progression, the date of death, or the date of last follow-up, with progression or death treated as target event.
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| E.2.2 | Secondary objectives of the trial |
• To evaluate overall response rate.
• To evaluate time to tumor response.
• To evaluate overall survival.
• To evaluate quality of life.
• To evaluate tolerability and safety.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Patients with advanced renal clear cell carcinoma
- who have failed prior cytokine-based therapy but are considered suitable for combination therapy with low dose cytokine-based therapy as planned in this study or
- who are unsuitable for full dose cytokine-based therapy but are considered suitable for combination therapy with low dose cytokine-based therapy as planned in this study
• At least 18 years of age
• Sufficient bone marrow function: neutrophils 2 x 109/l, hemoglobin ≥ 10 g/dl, and platelets 100 x 109/l
• Performance status ECOG 0-1
• Required laboratory results:
a) Liver function: Total bilirubin 1.5 x ULN, SGPT, SGOT 2.5 x ULN.
b) Renal function: serum creatinine 1.5 x ULN
c) PT-INR/PT 1.5 x ULN
• Normal cardiac function
• Life expectancy at least 3 months
• Written informed consent of the patient prior to screening procedures
• Patient must be available for treatment and follow-up
• Any previous surgery must have taken place more than 4 weeks prior to inclusion
• Previous radiation therapy must have involved less than 25% of bone marrow and must have been completed more than 4 weeks prior to inclusion.
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| E.4 | Principal exclusion criteria |
• Patients who require vitamin K antagonists except for low dose
• Active infection > grade 2 CTCAE version 3.0
• Known diagnosis of HIV, hepatitis B, or hepatitis C infection.
• Severe, unstable, or uncontrolled medical disease which would confound diagnoses or evaluations required by the protocol, including cardiac insufficiency (NYHA I–IV) ), symptomatic coronary artery disease, prior myocardial infarction, cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), uncontrolled hypertension, uncontrolled diabetes, chronic hepatic or renal disease, active uncontrolled infection and chronic inflammatory intestinal disease, auto-immune diseases.
• Prior radiation therapy > 25% of bone marrow
• Clinically symptomatic brain metastases
• Regular blood transfusions
• Treatment with other experimental substances within 30 days before study start
• Participation in another clinical trial within 30 days before study start or during the trial
• Unwilling or unable to comply with the protocol
• Pregnant or breastfeeding patients. Women of childbearing potential must have a negative pregnancy test performed 7 days prior start of treatment
• Women of child-bearing potential, men with reproductive potential enrolled in this trial must use adequate barrier birth control measures during the course of the trial contraception. Men should use adequate birth control for at least three months after the administration of sorafenib
• Patients with seizure disorders requiring medication (such as steroids or antiepileptics)
• Known hypersensitivity to one of the medications
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Major surgery within 4 weeks prior to start of study or incomplete wound healing
• Drug or alcohol abuse
• Psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results
• Known (at time of entry) gastrointestinal disorder, including malabsorbtion or active gastric ulcer, present to the extent that it might interfere with oral intake and absorption of study medication
• Any previous or concurrent malignancy or any cancer unless curatively treated > 3 years prior to study entry except cervical carcinoma in situ or adequately treated basal cell carcinoma.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression-free survival (PFS). PFS is defined as the time interval between the date of study entry and the date of progression, the date of death, or the date of last follow-up, with progression or death treated as target event. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
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| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| The study will approximately be finished in 4th quarter 2010 as the follow-up period is defined as 2 years after recruitment of the last patient. Patients will receive study medication as long as they show no signs of progression and as long as no withdrawal criteria are met (see chapter 5.6.6 in the protocol). |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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