Clinical Trial: MEDI4736 Combinations in Metastatic Renal Cell Carcinoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: MEDI4736 Combinations in Metastatic Renal Cell Carcinoma

Brief 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: aims to find the optimal dose of MEDI4736+savolitinib.
• Second stage: 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: patients will be tested for biomarkers before enrolment, and depending on the results will be allocated to one of 3 treatments (MEDI4736, savolitinib, or MEDI4736+tremelimumab) to see if certain biomarkers are linked to drug efficacy.

Detailed 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.

Sponsor: Queen Mary University of London

Current Primary Outcome:

• Identify Dose Limiting Toxicity -Phase Ib [ Time Frame: 6 months ]
  The endpoint of this objective is to identify Dose-Limiting Toxicity that occurs during the DLT assessment phase and is almost certainty/probably dose related and drug related .Toxicity that is clearly and directly related to the primary disease or another aetiology is excluded from this definition.
• Overall response (OR) in patients with metastatic clear cell renal cancer [ Time Frame: 18 months ]
  Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
• Overall response (OR) in patients with metastatic Papillary cell renal cancer [ Time Frame: 18 months ]
  Overall response rate based on RECIST V1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression
• Overall response (OR)in patients with metastatic renal cell cancer -Biomarker enrichment phase [ Time Frame: 11 months ]
  Overall response rate based on RECIST v1.1 measurements taken at baseline, week 4 and every 8 weeks until disease progression

Original Primary Outcome: Same as current

Current Secondary Outcome:

• De-escalation phase - PK-Cmax measurement [ Time Frame: 14 months ]
  Measurement of Cmax for MEDI4736 and savolitinib
• De-escalation phase - PK-Tmax measurement [ Time Frame: 14 months ]
  Measurement of tmax for MEDI4736 and savolitinib
• De-escalation phase -PK AUC (0-t) measurement [ Time Frame: 14 months ]
  Measurement of AUC(0-t)for MEDI4736 and savolitinib
• De-escalation phase - PK AUCs measurement [ Time Frame: 14 months ]
  Measurement of AUCs for MEDI4736 and savolitinib
• De-escalation phase -PK Css measurement [ Time Frame: 14 months ]
  Measurement of Css max for MEDI4736 and savolitinib
• De-escalation phase -PK Css min measurement [ Time Frame: 14 months ]
  Measurement of Css min. for MEDI4736 and savolitinib
• Expansion Phase (IIa) -Identify Progression free survival (PFS) [ Time Frame: 18 months ]
  PFS defined as the time from the date of registration to the date of the first documented tumour progression as per RECIST V1.1 or death from any cause , whichever occurs first
• Expansion Phase (IIa) -Identify overall Survival (OS) [ Time Frame: 18 months ]
  OS defined as the time from study entry to death from any cause.All deaths will be included whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact
• Expansion Phase (IIa) -Identify duration of response [ Time Frame: 18 months ]
  OS defined as the time from study entry to death from any cause.All deaths will be included whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact
• Biomarker positive patient analysis [ Time Frame: 11 months ]
  Patients that have test positive for C-met or PD-L1 alterations;OS defined as the time from study entry to death from any cause.All deaths will be included whether they occur on study or following treatment discontinuation. For patients who have not died, overall survival will be censored at the date of last contact
• Biomarker positive patient analysis [ Time Frame: 11 months ]
  Patients that have test positive for C-met or PD-L1 alterations; PFS defined as the time from the date of registration to the date of the first documented tumour progression as per RECIST V1.1 or death from any cause , whichever occurs first

Original Secondary Outcome: Same as current

Information By: Queen Mary University of London

Dates:
Date Received: February 22, 2016
Date Started: May 2016
Date Completion: September 2019
Last Updated: June 27, 2016
Last Verified: June 2016