A Trial of CXD101 in Combination With Nivolumab in Patients With Metastatic Microsatellite-Stable Colorectal Cancer

NCT03993626 | Unknown Phase 1 DMC

• 2 other identifiers: CTL-101-0232017-004509-42
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to assess the safety and efficacy of CXD101 in combination with the PD-1 Inhibitor Nivolumab in patients with metastatic, previously-treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (CRC). The primary hypothesis of this study is that CXD101 and anti-PD1 monoclonal antibody synergise the anti-tumour activity in MSS colorectal cancer patients (\~95% of CRC) who do not seem to respond to anti-PD1 or -PD-L1 immunotherapy alone.

Conditions

Colorectal Neoplasms Malignant

Outcome Measures

Primary Outcomes (1)

• Immune Disease Control Rate (iDCR)

  complete response \[iCR\], partial response \[iPR\], and stable disease \[iSD\] rate) after Seymour et al, 2017.

  6 months

Secondary Outcomes (4)

• 20-week immune-related progression-free survival (PFS)

  20 weeks

• Best Objective Response Rate

  6 months

• Overall Survival (OS)

  6 months

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  6 months

Study Arms (1)

CXD101 and Nivolumab combination

EXPERIMENTAL

* CXD101 will be presented as 10mg HPMC capsules and will be taken orally for 5 consecutive days repeated every three weeks on an outpatient basis. * Nivolumab will be presented as a 10 mg/mL solution in a single-dose vial, administered as iv infusion over 60 mins, repeated every two weeks. * CXD101 in combination with nivolumab will be administered in the Phase II component of the trial at doses determined in the Phase Ib component.

Drug: CXD101 in Combination With Nivolumab

Interventions

CXD101 in Combination With Nivolumab DRUG

HDAC inhibitor in combination with anti-PD-1 monoclonal antibody

CXD101 and Nivolumab combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Biopsy-confirmed MSS, MMR-P CRC. It is acceptable for this test to be performed on the archived primary colorectal cancer tissue and repeat biopsy for MSS testing is not required unless assay not yet performed and insufficient material available
• Previous first and second line treatment (unless contra-indicated) including use of oxaliplatin and irinotecan unless documented intolerance of these
• Measurable disease: longest diameter≥10mm (short axis ≥15mm for nodal lesions)
• Age \> 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Predicted life expectancy \> 3 months
• Adequate organ and bone marrow function: Hb\> 10.0g/dL (may be transfused to this level), neutrophils\> 1.5x10\^9/L and platelets\> 100x10\^9/L
• Female patients with reproductive potential must have a negative urine and serum pregnancy test prior to starting treatment. Both women of reproductive potential and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 5 months after discontinuation of treatment (i.e., combined oestrogen and progestogen ovulation inhibition; progestogen-only ovulation inhibition; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; or vasectomised partner). Oral contraception and parenteral hormonal contraceptives (patches, injectables and implants) that may be affected by enzyme-inducing drugs should only be used in combination with a barrier method. All males with partners of childbearing potential or whose partners are pregnant must use barrier contraception for the duration of dosing and for 5 months post-dosing.

You may not qualify if:

• Pregnant or breast feeding
• Pre-existing auto-immune conditions
• Medical conditions requiring systemic immunosuppression
• Previous treatment with an HDAC inhibitor or PD-1/PD-L1 inhibitor
• Other chemotherapy, radiotherapy, or investigational therapy within 4 weeks of the Screening /Baseline Assessment
• Unresolved clinically significant toxicity from a previous treatment
• History of recent active chronic inflammatory bowel disease and/or bowel obstruction
• Renal function: Serum creatinine \> 1.5 x ULN, or creatinine clearance \< 60mL/min (Cockcroft-Gault formula)
• Liver function: AST \> 3.0 x ULN; OR total bilirubin \> 1.5 x ULN
• Clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure NYHA Class III or IV, or pulmonary disease within 6 months
• Symptomatic brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis
• Clinically significant active infection requiring antibiotic or antiretroviral therapy
• History of malignancy other than MSS CRC, unless there is the expectation that the malignancy has been cured, and tumour specific treatment for the malignancy has not been administered within the previous 5 years
• History of pneumonitis, immune hepatitis or myocarditis, or current uncontrolled thyroid disease
• Current positive serology for Hepatitis B or C virus

Sponsors & Collaborators

• Celleron Therapeutics Ltd.: lead

Study Sites (1)

Celleron Therapeutics Ltd

Oxford, Oxfordshire, OX4 4GA, United Kingdom

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rachel Kerr, MD

  Department of Oncology, University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, single arm, phase 1b/2 safety; and efficacy using Simon Two-Stage analysis

Study Record Dates

• First Submitted: June 19, 2019
• First Posted: June 21, 2019
• Study Start: May 22, 2018
• Primary Completion: December 15, 2019
• Study Completion: June 15, 2020
• Last Updated: June 21, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)