AUSCor

Phase 1

• Conditions: Metastatic Colorectal Cancer; MedDRA version: 20.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002003-25-GB
• Lead Sponsor: Barts Health NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-21
• Last Update Posted: 21 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

1. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastas(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 1.1)

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:
•Serum aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]) or serum alanine aminotransferase (ALT; serum glutamic pyruvic transaminase [SGPT]) =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. Willing and able 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

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1.Palliative radiotherapy to non-target, metastatic lesions will be allowed.

2. Less than 4 weeks elapsed from prior chemotherapy to the time of inclusion. 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).

3. Treatment with any investigational drug within 30 days prior to inclusion.

4. Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy to the time of inclusion.

5. 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.

6. History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.

7. Other prior malignancy. 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 are allowed.

8. 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.

9. 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.

10. Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.

11. 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

12. Predisposing colonic or small bowel disorders in which the symptoms were uncontrolled as indicated by baseline of > 3 loose stools daily.

13. Treatment with concomitant anticonvulsant agents that are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.

14. Pregnant or breast-feeding women. Positive pregnancy test (serum or urine ß-HCG) for women of reproductive potential.

15. 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. The definition of effective method will be left to the investigator’s judgment.

16. For female patients enrolled in United Kingdom, the following methods of contraception are acceptable: oral contraceptives accompanied by the use of a second method of contraception, as it is not known how oral contraceptives interact with study medications or Intra Uterine Device (IUD) or women who are surgically sterile, or women who are post –menopausal or other reasons have no chance of becoming pregnant.

17. Urine protein-creatinine ratio (UPCR) >1 on morning spot urinalysis or proteinuria > 500 mg/24-h.

18. Serum creatinine > 1.5 x upper limit of normal (ULN).

19. 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine survival in patients with Dynamic Contrast Enhanced Ultrasound measured vascular shutdown in response to aflibercept compared to patients without vascular shutdown;Secondary Objective: Progression free survival in patients with Dynamic Contrast Enhanced (DCE)Ultrasound measured vascular shutdown compared to patient without vascular shutdown;Primary end point(s): Determine survival in patients with DCE-US measured vascular shutdown in response to Aflibercept compared to patients without vascular shutdown;Timepoint(s) of evaluation of this end point: Time measured from recruitment until the death / end of follow-up (1 year) / loss to follow-up.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Progression free survival (PFS) in patients with DCE-US measured vascular shutdown compared to patient without vascular shutdown;Timepoint(s) of evaluation of this end point: PFS measured from recruitment until the disease progression (using RECIST 1.1) or death whichever occurs first.