Colorectal Neoplasms MalignantPhase 1/2CAROSELLNCT03993626
A Trial of CXD101 in Combination With Nivolumab in Patients With Metastatic Microsatellite-Stable Colorectal Cancer
A Phase 1/2 study testing CXD101 in Combination With Nivolumab in people with Colorectal Neoplasms Malignant, run by Celleron Therapeutics Ltd. at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms Malignant
- What is being tested?
- CXD101 in Combination With Nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 May 2018to 15 Jun 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
- History of any allergy to excipients of the Investigational Medicinal Products (sodium citrate dihydrate, sodium chloride, mannitol, pentetic acid, Polysorbate 80, sodium hydroxide, hydrochloric acid, hydroxypropyl methylcellulose)
- Receipt of any live vaccine 30 days or fewer prior to administration of first dose IMP
- Inability to comply with the study protocol
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Celleron Therapeutics Ltd
Oxford, Oxfordshire, OX4 4GA
About this study
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
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.
Read the detailed description
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.
- Conditions
- Colorectal Neoplasms Malignant
- Being tested
- CXD101 in Combination With Nivolumab
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CXD101 in Combination With NivolumabDrug
HDAC inhibitor in combination with anti-PD-1 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: CXD101 in Combination With Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune Disease Control Rate (iDCR)
complete response [iCR], partial response [iPR], and stable disease [iSD] rate) after Seymour et al, 2017.
Measured: 6 months
Secondary outcomes (4)
20-week immune-related progression-free survival (PFS)
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.
Measured: 20 weeks
Best Objective Response Rate
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.
Measured: 6 months
Overall Survival (OS)
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.
Measured: 6 months
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start22 May 2018
- Primary completion15 Dec 2019 (estimated)
- Study completion15 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Neoplasms MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label, single arm, phase 1b/2 safety; and efficacy using Simon Two-Stage analysis
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celleron Therapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rachel Kerr, MD, Principal investigator, Department of Oncology, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03993626
- Sponsor's protocol ID
- CTL-101-023
- Other IDs
- 2017-004509-42, 2017
- Acronym
- CAROSELL
- Status last verified
- Jun 2019
- First submitted
- 19 Jun 2019
- Last updated
- 21 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03993626
- Acronym / sponsor ID
- CAROSELL / CTL-101-023
- Conditions
- Colorectal Neoplasms Malignant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Celleron Therapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- 22 May 2018 (actual)
- Primary completion
- 15 Dec 2019 (estimated)
- Study completion
- 15 Jun 2020 (estimated)
- First posted
- 21 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label, single arm, phase 1b/2 safety; and efficacy using Simon Two-Stage analysis
| Arm | Type | Receives |
|---|---|---|
| CXD101 and Nivolumab combination | Experimental | Drug: CXD101 in Combination With Nivolumab* 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CXD101 in Combination With NivolumabHDAC inhibitor in combination with anti-PD-1 monoclonal antibody | Drug | CXD101 and Nivolumab combination |
Primary outcome
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.
4 secondary outcomes
20-week immune-related progression-free survival (PFS)
Time frame: 20 weeks
Best Objective Response Rate
Time frame: 6 months
Overall Survival (OS)
Time frame: 6 months
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Kerr, MD principal investigator
Department of Oncology, University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CXD101 in Combination With Nivolumab in people with Colorectal Neoplasms Malignant, run by Celleron Therapeutics Ltd. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune Disease Control Rate (iDCR) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2019.