| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic and/or locally advanced Renal Clear Cell Carcinoma |
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| MedDRA Classification |
| 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 |
The aim of the STAR trial is to evaluate the use of a Modified sunitinib schedule compared to the Standard sunitinib schedule, in patients with locally advanced and/or metastatic renal cancer. The trial has three stages and should the trial not meet predetermined endpoints in its initial 2 stages (A and B), then recruitment will not continue to the third stage (stage C).
Stage A:
To establish the feasibility of performing the trial in terms of recruitment and whether the final required sample size is likely to be achieved and in a timely manner. Average monthly recruitment between months 10-21 inclusive will be used to determine this.
Stage B:
To provide an initial indication that the Modified sunitinib schedule (with planned treatment breaks) is not significantly worse than the Standard sunitinib schedule, by comparing the time until participants permanently stop sunitinib in each treatment arm.
Stages A B and C:
To show that the Modified sunitinib schedule is not wors |
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate how the Modified Schedule compared to the Standard Schedule impacts on:
• Summative Progression Free Interval (SPFI, adding together the time periods that the cancer is controlled for)
• Time to Strategy Failure (TSF, time until sunitinib is stopped permanently)
• Side Effects/toxicity (using CTCAE v.4.0)
• Quality of Life (QoL) questionnaires (Questionnaires to be used are FSKI, FACT-G, EQ-5D and EQ-VAS)
• Cost-effectiveness
• Progression free survival (PFS, how long participants live without their cancer progressing)
Translational sub-studies are also planned with the main aim of developing biomarkers to give an early prediction of response to sunitinib (please see more details in Section A13. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
-Functional Imaging Sub-Study: Dynamic Contrast Enhanced-MRI (DCE-MRI) Evaluation 01/04/2011 v1.0
-Computerised Tomography Imaging Sub-study 01/04/2011 v1.0
- Tissue studies 01/04/2011 v1.0
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| E.3 | Principal inclusion criteria |
1. Male or female aged ≥ 18 years old
2. Histological confirmation of predominantly clear cell renal cell cancer
3. Inoperable loco-regional and/or metastatic disease
4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease)
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
6. Uni-dimensionally measurable disease (RECIST criteria)
7. Full blood count:
• Haemoglobin (Hb) ≥ 9 g/dl
• Absolute Neutrophil Count (ANC) ≥ 1 x 109/l
• Platelets ≥ 80 x 109/l
8. Renal biochemistry:
• Measured or calculated GFR ≥ 30 ml/min
9. Hepatobiliary function
• Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN
• Bilirubin (BR) ≤ 1.5 x ULN, or ≤ x3 x ULN and direct BR ≤ 35% in patients with Gilbert’s syndrome
10. Able to provide written informed consent prior to any trial-specific procedures
11. Able and willing to comply with the terms of the protocol including:
• commencement of sunitinib within 3 days of randomisation
• temporarily stopping sunitinib if randomised to the DFIS arm
• capable of oral self-medication
• capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) questionnaires
12. If female and of child-bearing potential, must:
• have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding
• agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib
13. If male with a partner of child bearing potential, must
• agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib
Allowed situations include:
• primary renal cancer in-situ or previous nephrectomy,
• previous brain metastases treated with complete surgical resection or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible)
• previous treatment in the SORCE study providing on placebo arm and NOT active sorafenib arms (The SORCE trial is investigating whether treatment of renal cancer with sorafenib (also a tyrosine kinase inhibitor [TKI]) in the adjuvant setting is effective in reducing development of metastases in high risk patients compared with placebo. By agreement with the Chief Investigator of the SORCE trial, patients who have previously participated in SORCE and have progressed and are no longer on the SORCE trial, will be eligible for STAR, subject to confirmation (through unblinding) that that they received placebo and not active drug (sorafenib) on the SORCE study.
• previous radiotherapy and/or previous/ongoing bisphosphonates or bone- resorptive drugs (e.g. denosumab) for the treatment of symptomatic bony metastasis.
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|
| E.4 | Principal exclusion criteria |
1. Pulmonary or mediastinal disease causing obstruction or bleeding/haemoptysis
2. Patients with an estimated life expectancy of < 6 months
3. Known contraindications to sunitinib
4. No previous treatment with sunitinib or other tyrosine kinase inhibitor (including in the adjuvant setting)
5. Untreated brain metastases
6. Any concurrent or previous other invasive cancer that could confuse diagnosis (non-melanomatous skin cancer or superficial bladder cancer acceptable, for all other cases please discuss with CTRU)
7. Hypersensitivity to sunitinib
8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of sunitinib (see section 10.2 for further information on concomitant medications)
9. Poorly controlled hypertension despite maximal medical therapy
10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib therapy
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The study has two co-primary endpoints:
• 2 year Overall Survival
• Quality Adjusted Life Years averaged over trial recruitment and follow up
This trial of sunitinib in renal cancer will determine whether, by utilising the Modified Schedule of sunitinib (DFIS), survival benefits can be maintained, whilst other important outcomes, such as QoL and cost effectiveness, can be improved, compared to utilising the Standard Schedule of sunitinib (CCS). Oncological treatments for patients with incurable disease require assessment using standard measures of efficacy, such as survival. It is however recognized that other measures must also be taken into consideration including QoL and cost, particularly in the context of the economic constraints of the NHS. When seeking approval from NICE for a new treatment, all of these outcomes are considered. A composite co-primary endpoint (quality adjusted life years averaged over trial recruitment and follow up) is utilised to more accurately assess whether and how any detriment in survival might be balanced with improvements in quality of life and cost-effectiveness.
Stage-Specific Primary Endpoints
Stage A
Recruitment rate between months 10-21 of the trial (defined as the average recruitment rate per centre open per month between month 10 and 21 of the trial inclusive).
Stage B
Time to Strategy Failure, defined as time from randomisation until:
a) death;
b) disease progression on sunitinib in the CCS arm;
c) disease progression assuming no further disease response or stabilisation on subsequent sunitinib occurs, in DFIS arm, or
d) patient requires use of a new systemic anti-cancer agent for RCC (end point measured at the first of either time of disease progression or time of initiation of new agent), or
e) disease progression during a planned treatment break and receiving no further sunitinib within 4 weeks.
Stages A B and C
• 2 year Overall Survival (defined as the time from randomisation to the trial to death from any cause or last follow-up. Analyses are targeted to look at differences in 2 year survival, but all follow-up will be incorporated).
• Quality Adjusted Life Years averaged over trial recruitment and follow up
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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 | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Comparator is conventional continuation strategy using same IMP (cf. to drug-free interval strategy) |
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| 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 | 38 |
| 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 | Yes |
| 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
|
The end of the trial is defined as the date all 2 year follow-up assessments are completed for all trial participants evaluable at this timepoint.
Any participants still responding to their protocol-defined treatment strategy after their 2 year follow-up assessment will continue to receive sunitinib treatment as per 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 | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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