A phase II double-blind, randomised controlled trial of VEGF inhibitor axitinib monotherapy with early dynamic contrast-enhanced ultrasound monitoring in chemo-refractory third-line metastatic colorectal cancer

• Register: ISRCTN
• Last refreshed on: 3 August 2020
• Main ID: ISRCTN70833965
• Date of registration: 25/10/2013
• Prospective Registration: No
• Primary sponsor: Imperial College of Science, Technology and Medicine (UK)
• Public title: A phase II double-blind, randomised controlled trial of VEGF inhibitor axitinib monotherapy with early dynamic contrast-enhanced ultrasound monitoring in chemo-refractory third-line metastatic colorectal cancer
• Scientific title: A phase II double-blind, randomised controlled trial of VEGF inhibitor axitinib monotherapy with early dynamic contrast-enhanced ultrasound monitoring in chemo-refractory third-line metastatic colorectal cancer
• Date of first enrolment: 05/09/2012
• Target sample size: 51
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN70833965
• Study type: Interventional
• Study design: Randomised interventional treatment trial (Treatment)
• Phase: Phase II

Countries of recruitment

United Kingdom

Contacts

• Name: Mohana Suppiah

Key inclusion & exclusion criteria

Inclusion criteria:
Participants must meet all of the following inclusion criteria to eligible for enrollment into the trial:
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, chemoembolization, ethanol or cryoablation.
2. Failed at least two chemotherapy regimens in advanced disease.
3. Evidence of unidimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
4. Male and female, 18 years of age or older.
5. ECOG performance status of 0 or 1.
6. Resolution of all acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade =1.
7. Adequate organ function as defined by the following criteria:
7.1. Serum aspartate aminotransferase (AST¿ serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine aminotransferase (ALT¿ serum glutamic pyruvic transaminase [SGPT]) =2.5 x upper limit of normal (ULN). For patients with liver metastases, <5 x ULN.
7.2. Total serum bilirubin <1.5 x ULN
7.3. Serum albumin =3.0 g/dL
7.4. Absolute neutrophil count =1500/µL
7.5. Platelets =100,000/µL
7.6. Haemoglobin =9.0 g/dL
7.7. Serum creatinine =1.5 x ULN
8. Signed and dated informed consent form
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
10. At least 2 weeks since the end of prior systemic treatment (4 weeks for Bevacizumab-containing regimens), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 3.0 grade =1 or back to baseline except for alopecia or hypothyroidism.
11. No evidence of pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mmHg, and the baseline diastolic blood pressure readings must be =90 mmHg. Patients whose hypertension is controlled by anti-hypertensive therapies are eligible.
12. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
13. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrolment.

Exclusion criteria:
Participants must be excluded if they present with any of the following exclusion criteria:
1. Non-exposed to both oxaliplatin and irinotecan FP based cytotoxic chemotherapy (prior pelvic radiation therapy including adjuvant or neoadjuvant chemoradiation therapy for resected rectal cancer is allowed provided it is completed within 4 weeks prior to study entry)
2. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St John?s wort). Current use or anticipated need for treatment with drugs that are known CYP3A4 inhibitors (i.e., grapefruit juice, ketoconazole, nefazodone, itraconazole, miconazole, erythromycin, clarithromycin, telithromycin, verapamil, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)
3. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
4. Non-English speaking
5. Pregnancy, breastfeeding, or unwillingness/inability to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for up to 3 months after discontinuing study drug if of reproductive potential.
6. Hypertension uncontrolled by medication (>150/100 mmHg despite optimal medical therapy).
7. Diagnosis of any second malignancy within the last 3 years that is potentially liable to interfere with study outcomes (basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma and hormone-controlled locally advanced prostate cancer that has been adequately treated with no evidence of recurrent disease for 12 months, are allowed)
8. Prior surgery or IMP within 4 weeks prior to study entry
9. Current treatment within another therapeutic clinical trial.


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Topic: National Cancer Research Network; Subtopic: Colorectal Cancer; Disease: Colon, Rectum
Cancer
Malignant neoplasm of colon

Intervention(s)

Arm A: Axitinib monotherapy started in all patients at 5 mg bd, and increased fortnightly by a dose level as tolerated to a maximum dose of 10 mg bd.

Arm B: Placebo at 2:1 ratio to treatment

Axitinib/ Placebo +CEPHI, Axitinib, a substituted indazole derivative, is an oral, potent, and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3

After 4 hours of fasting, a DCE-US scan is performed on each subject in the supine position using an iU22 ultrasound scanner (Philips Healthcare, Andover, MA) with a C5-1 curvilinear transducer. The probe is held still in the right intercostal space in order to visualise the porta hepatis. This allows simultaneous visualization of the hepat.

Study Entry : Single Randomisation only

Primary Outcome(s)

To demonstrate a progression-free survival to Axitinib monotherapy in metastatic colorectal cancer

Secondary Outcome(s)

Not provided at time of registration

Secondary ID(s)

NCT04355156

2011-002598-49

12424

Source(s) of Monetary Support

Pfizer Ltd

Ethics review

Status:
Approval date:
Contact:

12/LO/0066; First MREC approval date 23/04/2012

Results

• Results available: Yes
• Date Completed: 31/03/2015