A phase I/II dose finding study evaluating the safety and tolerability of CAPecitabine and AflIbercept in patients with unresectable metasTAtic colorectaL cancer deemed unsuitable for doublet/ triplet chemotherapy.

Phase 1

• Conditions: 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: EUCTR2013-002308-15-GB
• Lead Sponsor: Guys & St. Thomas' NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10-03
• Last Update Posted: 19 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Histologically confirmed colorectal cancer with evidence of metastatic disease
Adequate medical fitness to undergo fluoropyrimidine-based chemotherapy.
No known dihydropyrimidine dehydrogenase deficiency.
Adequate bone marrow function with:
platelets > 100 x 109/l; WBC > 3 x 109/l; neutrophils > 1.5 x 109/l; Hb > 9 g/dl
Serum bilirubin < 1.5 x upper limit of institutional normal range (ULN), alkaline phosphatase < 5 x ULN and transaminases < 3 x ULN unless liver metastasis then < 5 x ULN.
Serum creatinine = 1.5 x ULN or creatinine clearance > 50ml/min
Proteinuria < 2+ (dipstick urinalysis) or = 1g/24hour.
For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment,
Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.
Recovery from any treatment related grade 3/4 non-haematological toxicity (except alopecia and fatigue) to baseline or = grade 1
Absence of pre-existing liver dysfunction of Childs-Pugh B or worse
Written informed consent
Life expectancy > 3 months
Age = 18 years

Phase I study specific criteria
WHO performance status 0 – 1
Progressive disease after at least first line chemotherapy treatment
Previous fluoropyrimidine therapy has not required dose reduction of greater than 25%, significant delay (= 7 days) or stopped treatment due to fluoropyrimidine toxicity

Phase 2 specific criteria
WHO performance status 0 – 2
? Patients not deemed suitable for doublet/triplet combination chemotherapy.
? No previous treatment for mCRC.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

Known evidence of brain metastases
o Liver-only metastatic disease deemed to be resectable
o LVEF <50%
o Patients who did not previously tolerate IV 5-FU or capecitabine (required dose reduction, significant delay (= 7days) or stopped treatment due to fluoropyrimidine toxicity
Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding/haemorrhage (unless due to resected tumour), treatment resistant peptic ulcer disease, erosive oesophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism or other uncontrolled thrombo-embolic event.
o Any of the following within 6 months prior to inclusion: myocardial infarction, acute coronary syndrome, unstable angina pectoris, coronary revascularisation (PCI or CABG), NYHA class III or IV congestive heart failure, stroke or transient ischaemic attack.
o Any patient who has undergone major surgery <1month prior to trial entry.
o Uncontrolled hypertension (grade 3 /4)
o Significant proteinuria (=2+ on dipstick or =1g/24hour)
o Significant bleeding diathesis or significant underlying coagulopathy (INR>1.5) in the absence of vitamin K antagonist therapy.
o Intolerance to loperamide
o Previous history of gastrointestinal fistula or perforation
o Evidence of bowel obstruction
o Clinically relevant history of drug or alcohol abuse
o Serious uncontrolled inter current illness including poorly controlled diabetes mellitus
o HIV, HBV or HCV infection.
o Pregnancy or lactation. Men and women of child-bearing potential must use adequate contraception
Any psychological, familial, sociological or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.

Study & Design

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