A Trial of CXD101 in Combination With Nivolumab in Patients With Metastatic Microsatellite-Stable Colorectal Cancer (CAROSELL)
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|ClinicalTrials.gov Identifier: NCT03993626|
Recruitment Status : Active, not recruiting
First Posted : June 21, 2019
Last Update Posted : June 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Neoplasms Malignant||Drug: CXD101 in Combination With Nivolumab||Phase 1 Phase 2|
Phase Ib trial: This single-arm dose escalation trial will determine the safety, tolerability and dose limiting toxicities (DLT) and therefore the maximum tolerated dose (MTD) of repeat doses of nivolumab combined with CXD101. The incidence and severity of adverse events (evaluated according to CTCAE version 4.03), vital signs, ECG parameters, biochemistry, haematology and urinalysis will be recorded to determine tolerability.
Dose escalation will proceed as follows:
Dose Level 1 Nivolumab 240 mg iv q 2 weekly; with CXD101 30 mg (20mg mane, 10mg nocte) po for 5 days q 3 weekly (n=3-6) with both drugs commencing on the same day in cycle 1.
Dose Level 2 Nivolumab 240 mg iv q 2 weekly; with CXD101 40mg (20 mg bid) po for 5 days q 3 weekly (n=6) with both drugs commencing on the same day in cycle 1.
A maximum of 15 subjects will be required.
Phase II trial: Following completion of the Phase Ib study, a Phase II CXD101/ nivolumab combination dose will be selected by the Data and Safety Monitoring Committee. Up to a further 40 subjects will then be treated at the selected Phase II CXD101/ nivolumab combination dose. Subjects may continue to receive CXD101/ nivolumab until complete response, disease progression, unacceptable toxicity, withdrawal of consent, or other medical problems supervene.
Efficacy will be measured using Immune Response Evaluation Criteria in Solid Tumours (iRECIST) Imaging studies, typically CT scan of chest, abdomen & pelvis, supplemented by MRI of liver when required, will be performed at Baseline and after every 6 weeks, with objective confirmation of response 6 weeks (+/- 1 week) after observation. Safety parameters will be assessed as in the Phase I study. In addition there will be a series of translational analyses including correlation of tumour biomarker expression with response.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open label, single arm, phase 1b/2 safety; and efficacy using Simon Two-Stage analysis|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination With the PD-1 Inhibitor Nivolumab in Patients With Metastatic, Previously-Treated, Microsatellite-Stable Colorectal Carcinoma|
|Actual Study Start Date :||May 22, 2018|
|Estimated Primary Completion Date :||December 15, 2019|
|Estimated Study Completion Date :||June 15, 2020|
Experimental: CXD101 and Nivolumab combination
Drug: CXD101 in Combination With Nivolumab
HDAC inhibitor in combination with anti-PD-1 monoclonal antibody
- Immune Disease Control Rate (iDCR) [ Time Frame: 6 months ]complete response [iCR], partial response [iPR], and stable disease [iSD] rate) after Seymour et al, 2017.
- 20-week immune-related progression-free survival (PFS) [ Time Frame: 20 weeks ]
Progression-free survival will be measured from the date of first dose until death from any cause, with measurement cut-off at 20 weeks. Subjects who discontinue from treatment will classed as "censored" at the last timepoint when their PFS status was known. Subjects who discontinue from the study will be classed as "censored" at the time they discontinue.
A Kaplan-Meier survival curve will be plotted and the 20-week PFS rate determined, with a 95% confidence interval.
- Best Objective Response Rate [ Time Frame: 6 months ]iCR + iPR / iCR + iPR + iSD + iPD x 100. The Objective Response Rate will be calculated as the combined percentage of subjects who have achieved as best response: complete response, or partial response.
- Overall Survival (OS) [ Time Frame: 6 months ]
Overall Survival will be measured from the date of first dose until death from any cause. Subjects who discontinue from treatment will be followed up for survival but will be classed as "censored" at the last timepoint when their survival status was known. Subjects who discontinue from the study will be classed as "censored" at the time they discontinue.
A Kaplan-Meier survival curve will be plotted for overall survival.
- Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: 6 months ]AEs may be directly observed, evident in laboratory or diagnostic results, reported spontaneously by the subject, or by questioning the subject at each study visit. All subjects who complete screening, receive at least one dose of study medication and who have at least one safety assessment (including "death") will be in the Safety Set.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03993626
|Celleron Therapeutics Ltd|
|Oxford, Oxfordshire, United Kingdom, OX4 4GA|
|Principal Investigator:||Rachel Kerr, MD||Department of Oncology, University of Oxford|