I235

I235 Details
Status: Closed
Activation Date: 2018AUG28
Closing Date: 2019AUG02
Phase: II

Description: A Phase II Open Label, Randomized Non-Comparative Trial of Nivolumab Alone or in Combination with Ipilimumab for the Treatment of Patients with Advanced Hypermutated Solid Tumors Detected by a Blood Based Assay

Eligibility: Histologically confirmed advanced metastatic or unresectable solid tumors with POLE/POLD1 mutations. Available tissue block from primary or metastatic tumor. Measurable disease per RECIST 1.1. Received at least 1 standard cancer therapy for their tumour type and progressed on most recent regimen. Adjuvant/neoadjuvant therapy is considered a prior therapy if recurrence within 1 year. Can be treatment naiive if patient has refused standard treatment or there is no standard treatment for their cancer. No prior immunotherapy. No primary CNS tumors. No prior autoimmune or inflammatory disorders within the past 3 years. No history of primary immunodeficiency, allogeneic organ transplant that requires therapeutic use of IO agents within 14 days. No hypersensitivity to nivolumab or ipilimumab or any excipient. No active brain metastases or leptomeningeal metastases. No serious illnesses or medical conditions which would not permit the patient to be managed per protocol.

Objective: Primary - Objective response rate by RECIST 1.1 of nivolumab alone and of nivolumab combined with ipilimumab in randomized patients with advanced solid tumors with detectable POLE or POLD1 mutations as determined by cfDNA. Secondary - Evaluate objective response rate of nivolumab alone and nivolumab in combination with ipilimumab in all treated patients with detectable POL mutations in either blood or tissue. Evaluate duration of response. Assess safety and characterize toxicities of nivolumab combined with ipilimumab and nivolumab alone. Assess the correlation between POLE/POLD1 mutations in tumor and POLE/POLD1 mutations in blood. Evaluate response by iRECIST. Exploratory - Determine Progression Free Survival and Overall Survival. Determine correlation between POLE/POLD1 mutations occurring within or outside of the exonuclease domain and tumor mutation load by whole exome and RNA sequencing. Determine correlation between tumour mutation burden in cfDNA and tumor tissue.

Participation: Limited to invited centres

Lay Description: The purpose of the pre-study screening is to test for POLE or POLD1 genetic biomarkers in blood to see if patients can take part in the main study. The purpose of the main study is to find out what effects two new immunotherapy drugs (nivolumab or nivolumab given in combination with ipilimumab) have on people with the genetic biomarkers (POLE or POLD1). In addition, these results may be used to develop a diagnostic test (any kind of medical procedure that helps in the diagnosis of disease or help guide treatment decisions). This study will also look at the side effects of these two new immunotherapy drugs. The researchers are also looking for ways to help predict who is most likely to be helped by these drugs by testing for other gene changes in tumour and blood samples.

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Disease Site	Trial Code	Patients Accrued	Patients - Blocks	Patients - Slides	Patients - Blocks and/or Slides
IND	I235	107	0	4	4

Hide TMA Samples

(Core size is 0.6 mm)

Disease Site	Trial Code	Patients Accrued	TMA Blocks	Patients on TMA Blocks
IND	I235	107	0	0

Hide Fluid Samples

Disease Site	Trial Code	Patients Accrued	Patients - Whole Blood	Patients - Cellular Component of Blood	Patients - DNA extracted from Blood	Patients - RNA extracted from Blood	Patients - Plasma	Patients - Serum	Patients - Urine	Patients - Buccal
IND	I235	107	0	0	0	0	3	3	0	0