MEDI4736 Combinations in Metastatic Renal Cell Carcinoma
United Kingdom69 participantsStarted 2016-05-03
Plain-language summary
This study is being carried out to see if the drugs MEDI4736, Savolitinib and Tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
If a patient is eligible for the study and decides to take part, they will be enrolled into one of 3 stages of the study.
* First stage \[CLOSED TO RECRUITMENT\]: aims to find the optimal dose of MEDI4736+savolitinib.
* Second stage \[CLOSED TO RECRUITMENT\]: patients with papillary cell cancer will be treated with MEDI4736+savolitinib. Patients with clear cell cancer will be randomised to one of four treatment arms and receive MEDI4736, savolitinib, MEDI4736+savolitinib, or MEDI4736+tremelimumab.
* Third stage \[NOT YET OPEN TO RECRUITMENT\]: patients will be tested for biomarkers before enrolment, and depending on the results will be allocated to one of 2 treatments (MEDI4736 alone or MEDI4736+tremelimumab) to see if certain biomarkers are linked to drug efficacy.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Written informed consent prior to performing any protocol-related procedures, including study specific screening procedures.
. Age ≥ 18 years at the time of registration/enrolment.
. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
. Life expectancy ≥12 weeks
. Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (stage IV) renal cell cancer with a component of either clear cell cancer or papillary cancer. Patients with a component of both must be enrolled into the cohort with the predominant tumour type.
. Clear cell renal cancer patients must have experienced progressive disease after exposure to Vascular Endothelial growth rate (VEGF) targeted therapy.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Identify Dose Limiting Toxicity -Phase Ib
Timeframe: 6 months
2
Overall response (OR) in patients with metastatic clear cell renal cancer
Timeframe: 18 months
3
Overall response (OR) in patients with metastatic Papillary cell renal cancer
Timeframe: 18 months
4
Overall response (OR)in patients with metastatic renal cell cancer -Biomarker enrichment phase
. Sarcomatoid cell renal cancer patients must have experienced progressive disease after exposure to VEGF targeted therapy.
. Papillary cell renal cancer patients must be considered to be VEGF treatment naive or treatment refractory to be eligible.
Exclusion criteria
. Participation in another clinical study with an investigational product within 28 days prior to enrolment in the study.
. Any previous treatment with an anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody (including MEDI4736), CD137 agonists, c-MET inhibitors or pathway-targeting agents, or CTLA-4. Patients with limited c-MET inhibitor exposure must be discussed with the study medical monitor.
. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) within 2 weeks or five half-lives of the anti-cancer therapy prior to the first dose of study drug, or radical radiotherapy within 4 weeks prior to the first dose of study drug.
. Patients receiving strong inducers of CYP3A4, strong inhibitors of CYP3A4 or CYP1A2 or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort) are excluded from enrolment in the study (see Appendix I).
. Currently receiving treatment with therapeutic doses of warfarin sodium. LMWH is allowed.
. Current or prior use of immunosuppressive medication within 21 days before the first dose of MEDI4736 or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\] -2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.
. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736 or tremelimumab or anticipation that such a live, attenuated vaccine will be required during the study.