Colorectal CancerPhase 2AUSCORNCT03264274
Trial of Aflibercept Monotherapy With DCE-US in Chemorefractory Metastatic Colorectal Cancer
A Phase 2 study testing Aflibercept and Dynamic Contrast Enhanced Ultrasound in people with Colorectal Cancer, run by Barts & The London NHS Trust.
Trial summary
Various antiangiogenic agents have a modest effect in prolonging overall survival in solid tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab significantly prolongs survival, but it is not effective in the majority of patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Aflibercept and Dynamic Contrast Enhanced Ultrasound
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 6 Feb 2017to 6 Feb 2017
- Phase
- Phase 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
- 1. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastasis(es), at least one of which should not have had any focal therapy including radiofrequency ablation.
- 2. Evidence of uni-dimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumours (RECIST).
- 3. 18 years of age or older.
- 4. ECOG performance status of < 3.
- 5. Failed (or intolerant of) at least 2 chemotherapy regimens in advanced disease and resolution of any acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade ≤1. No other alternative available effective treatment options.
- 6. Adequate organ function as defined by the following criteria:
Show all 17Show fewer
- Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN).
- Total serum bilirubin <1.5 x ULN
- Serum albumin ≥25mg/dl
- Absolute neutrophil count ≥1000/µL
- Platelets ≥75, 000/µL
- Haemoglobin ≥9.0 g/dL
- Serum creatinine ≤1.5 x ULN
- 7. Willingness and ability to provide fully informed consent to participate in the study.
- 8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- 9. Willingness to maintain good oral hygiene and receive regular dental assessments. No evidence of oral infection or planned dental surgery (excluding fillings).
- 10. Willingness to donate archival diagnostic tissue for translational research.
Who cannot join
- Palliative radiotherapy to non-target, metastatic lesions will be allowed.
- Less than 4 weeks following major surgery to the time of inclusion or until the surgical wound is fully healed, whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed).
- Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy to the time of inclusion.
- Treatment with any investigational drug within 30 days prior to inclusion.
- Adverse events (with exception of alopecia, peripheral sensory neuropathy and those listed in specific exclusion criteria) from any prior anti-cancer therapy of grade >1 (National Cancer Institute Common terminology Criteria [NCI CTCAE] v.4.0) at the time of inclusion.
- History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
Show all 22Show fewer
- Other prior malignancy, with the exception of adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the patient has been disease free for > 5 years.
- Any of the following within 6 months prior to inclusion: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack.
- Any of the following within 3 months prior to inclusion: Grade 3-4 gastrointestinal bleeding/haemorrhage, treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thromboembolic event.
- Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
- Any severe acute or chronic medical condition, which could impair the ability of the patient to participate to the study or to interfere with interpretation of study results.
- Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled as indicated by baseline of > 3 loose stools daily.
- Treatment with concomitant anticonvulsant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
- Pregnant or breast-feeding women. Positive pregnancy test (serum or urine β-HCG) for women of reproductive potential.
- Patients with reproductive potential (female and male) who do not agree to use an accepted effective method of contraception during the study treatment period and for at least 6 months following completion of study treatment. Effective method is defined in section 12.16.
- Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.
- Serum creatinine > 1.5 x upper limit of normal (ULN).
- Uncontrolled hypertension (defined as blood pressure > 140/90 mmHg or systolic blood pressure >160 mmHg when diastolic blood pressure < 90 mmHg, on at least 2 repeated determinations on separate days, or upon clinical judgment) within 3 months prior to study inclusion.
- Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range INR (>3) within the 4 weeks prior to inclusion.
- Evidence of clinically significant bleeding diathesis or underlying coagulopathy (e.g. INR>1.5 without vitamin K antagonist therapy), non-healing wound.
- Allergy to sulphur.
- Use of IV bisphosphonates or dental surgery in the previous 60 days, or any planned use of IV bisphosphonates or dental surgery.
About this study
Official title: A Phase II Trial of Aflibercept Monotherapy With Early Dynamic Contrast Enhanced Ultrasound Monitoring in Chemorefractory Metastatic Colorectal Cancer
Various antiangiogenic agents have a modest effect in prolonging overall survival in solid tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab significantly prolongs survival, but it is not effective in the majority of patients. Biomarker studies using tumour tissue and blood have failed to define a consistent biomarker that correlates with a beneficial effect of bevacizumab on survival. DCE-MRI can detect changes in tumour blood flow which, in early phase drug studies, correlated with subsequent tumour responses, but is too expensive and time consuming to be used in larger scale trials. DCE-US is a promising biomarker for use in this group of patients with antiangiogenic agents, as detailed above. The investigators wish to use this technique as a predictive biomarker for any effects Aflibercept has on OS and PFS in patients with metastatic colorectal cancer refractory to standard treatment.
- Conditions
- Colorectal Cancer
- Being tested
- Aflibercept, Dynamic Contrast Enhanced Ultrasound
- Keywords
- Colorectal, Metastatic, Chemorefractory, Ultrasound, Aflibercept
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfliberceptDrug
Also called Zaltrap
Antiangiogenic
Dynamic Contrast Enhanced UltrasoundProcedure or surgery
Also called DCE-US
DCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept + DCE-US | Other | Aflibercept: 4mg/kg IV every 2 weeks until discontinuation due to progression. DCE-US before treatment, and at 2 weeks and 8 weeks after the first Aflibercept administration. Receives: Drug: Aflibercept; Procedure: Dynamic Contrast Enhanced Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: 1 year
Secondary outcomes (1)
Progression-free survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2017
- Study start6 Feb 2017
- Primary completion6 Feb 2017
- Study completion6 Feb 2017
Why it stopped: Funding restrictions - study never opened to recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm study
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi
- Responsible party
- Sponsor
- Investigators
- David David, Principal investigator, Barts & The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03264274
- Sponsor's protocol ID
- 9301
- Other IDs
- 2014-002003-25, 2014
- Acronym
- AUSCOR
- Status last verified
- Aug 2017
- First submitted
- 31 Mar 2016
- Last updated
- 31 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No data collected. Study closed before recruitment.
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Aflibercept Monotherapy With Early Dynamic Contrast Enhanced Ultrasound Monitoring in Chemorefractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03264274
- Acronym / sponsor ID
- AUSCOR / 9301
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal, Metastatic, Chemorefractory, Ultrasound, Aflibercept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding restrictions - study never opened to recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Barts & The London NHS TrustUniversity, hospital or other
- Collaborators
- Sanofi
- Study start
- 6 Feb 2017 (actual)
- Primary completion
- 6 Feb 2017 (actual)
- Study completion
- 6 Feb 2017 (actual)
- First posted
- 29 Aug 2017 (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.
Various antiangiogenic agents have a modest effect in prolonging overall survival in solid tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab significantly prolongs survival, but it is not effective in the majority of patients. Biomarker studies using tumour tissue and blood have failed to define a consistent biomarker that correlates with a beneficial effect of bevacizumab on survival. DCE-MRI can detect changes in tumour blood flow which, in early phase drug studies, correlated with subsequent tumour responses, but is too expensive and time consuming to be used in larger scale trials. DCE-US is a promising biomarker for use in this group of patients with antiangiogenic agents, as detailed above. The investigators wish to use this technique as a predictive biomarker for any effects Aflibercept has on OS and PFS in patients with metastatic colorectal cancer refractory to standard treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm study
| Arm | Type | Receives |
|---|---|---|
| Aflibercept + DCE-US | Other | Drug: Aflibercept, Procedure: Dynamic Contrast Enhanced UltrasoundAflibercept: 4mg/kg IV every 2 weeks until discontinuation due to progression. DCE-US before treatment, and at 2 weeks and 8 weeks after the first Aflibercept administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 1. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastasis(es), at least one of which should not have had any focal therapy including radiofrequency ablation.
- 2. Evidence of uni-dimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumours (RECIST).
- 3. 18 years of age or older.
- 4. ECOG performance status of < 3.
- 5. Failed (or intolerant of) at least 2 chemotherapy regimens in advanced disease and resolution of any acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade ≤1. No other alternative available effective treatment options.
Key exclusion criteria (22 listed)
- Palliative radiotherapy to non-target, metastatic lesions will be allowed.
- Less than 4 weeks following major surgery to the time of inclusion or until the surgical wound is fully healed, whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed).
- Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy to the time of inclusion.
- Treatment with any investigational drug within 30 days prior to inclusion.
- Adverse events (with exception of alopecia, peripheral sensory neuropathy and those listed in specific exclusion criteria) from any prior anti-cancer therapy of grade >1 (National Cancer Institute Common terminology Criteria [NCI CTCAE] v.4.0) at the time of inclusion.
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 |
|---|---|---|
| AfliberceptAlso: ZaltrapAntiangiogenic | Drug | Aflibercept + DCE-US |
| Dynamic Contrast Enhanced UltrasoundAlso: DCE-USDCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment. | Procedure or surgery | Aflibercept + DCE-US |
Primary outcome
Overall survival
Time frame: 1 year
1 secondary outcome
Progression-free survival
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2017.
- Individual participant dataSharing planned: No. No data collected. Study closed before recruitment.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
David David principal investigator
Barts & The London NHS Trust
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aflibercept and Dynamic Contrast Enhanced Ultrasound in people with Colorectal Cancer, run by Barts & The London NHS Trust.
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 17 inclusion and 22 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: withdrawn, as of the sponsor's last update on 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Overall survival (time frame: 1 year). 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 31 Aug 2017.