Trial of Aflibercept Monotherapy With DCE-US in Chemorefractory Metastatic Colorectal Cancer

NCT03264274 | Withdrawn Phase 2

• 2 other identifiers: 93012014-002003-25
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Keywords

Colorectal; Metastatic; Chemorefractory; Ultrasound; Aflibercept

Outcome Measures

Primary Outcomes (1)

• Overall survival

  1 year

Secondary Outcomes (1)

• Progression-free survival

  1 year

Study Arms (1)

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.

Drug: Aflibercept; Procedure: Dynamic Contrast Enhanced Ultrasound

Interventions

Aflibercept DRUG

Antiangiogenic

Also known as: Zaltrap

Aflibercept + DCE-US

Dynamic Contrast Enhanced Ultrasound PROCEDURE

DCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment.

Also known as: DCE-US

Aflibercept + DCE-US

Eligibility Criteria

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

You may qualify if:

• \. 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.
• \. Evidence of uni-dimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumours (RECIST).
• \. 18 years of age or older.
• \. ECOG performance status of \< 3.
• \. 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.
• \. Adequate organ function as defined by the following criteria:
• 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
• \. Willingness and ability to provide fully informed consent to participate in the study.
• \. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• Palliative radiotherapy to non-target, metastatic lesions will be allowed.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Sanofi: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David David

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm study

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: August 29, 2017
• Study Start: February 6, 2017
• Primary Completion: February 6, 2017
• Study Completion: February 6, 2017
• Last Updated: August 31, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share