Axitinib Monotherapy With Early Dynamic Contrast Enhanced Ultrasound Monitoring in Chemorefractory Third Line Metastatic Colorectal Cancer

NCT04355156 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: WS9139752011-002598-49
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of Axitinib versus placebo as monotherapy for people with colorectal cancer who have liver metastases and who have relapsed within 6 months of their last chemotherapy regime. The research will also look at the potential of CEHPI (Contrast Enhanced Hepatic Perfusion Index) reduction, a technique developed for this research to measure the changes in how the blood vessels pump blood into the different liver metastases (tumours) and therefore to assess and predict response to treatment.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Difference in median overall survival between patients in the Axitinib arm who achieve a reduction in CEHPI index of at least 20% from baseline and those who do not achieve in both Axitinib and placebo arms

  Through study completion, an average of 1 year

Secondary Outcomes (3)

• Hazard Ratio for Overall Survival Based on CEHPI Response

  Through study completion, an average of 1 year

• Hazard Ratio for Progression Free Survival

  Through study completion, an average of 1 year

• Hazard Ratio for Progression Free Survival Between CEHPI Responders Compared to Non-Responders in Axitinib Group

  Through study completion, an average of 1 year

Study Arms (2)

Axitinib

EXPERIMENTAL

small molecule multi-kinase inhibitor

Drug: Axitinib

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Axitinib DRUG

* All patients randomised to this arm will receive 3mg BD, and increased at 2 weeks to 5mg BD * Outpatient monitoring at 2 week intervals for a minimum of 8 weeks, with 2 weekly liver contrast ultrasound for assessment of differential blood supply (CEHPI) * At 8 weeks, after tumour CT RECIST assessments, responders will continue monotherapy. In non-responders, those with disease progression, monotherapy can be continued if patient chooses to continue and if tolerated

Axitinib

Placebo DRUG

* All patients receiving placebo will receive tablets to take BD * Outpatient monitoring at 2 week intervals for a minimum of 8 weeks, with 2 weekly liver contrast ultrasound for assessment of differential blood supply (CEHPI)

Placebo

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 metastas(es). At least one of which should not have had any focal therapy including radiofrequency ablation, chemoembolization, ethanol or cryoablation.
• Failed at least 2 chemotherapy regimens in advanced disease.
• Evidence of unidimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
• years of age or older.
• ECOG performance status of 0 or 1.
• Resolution of all acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade ≤1.
• Adequate organ function as defined by the following criteria:
• 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.
• Total serum bilirubin \<1.5 x ULN Serum albumin ≥3.0 g/dL Absolute neutrophil count ≥1500/µL Platelets ≥100,000/µL Haemoglobin ≥9.0 g/dL Serum creatinine ≤1.5 x ULN
• Signed and dated informed consent form
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient reported outcome measures.
• 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.
• No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
• 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.

You may not qualify if:

• The presence of any of the following will exclude a patient from enrolment:
• Non-exposed to both oxaliplatin and irinotecan FP based cytotoxic chemotherapy (prior pelvic radiation therapy including adjuvant or neoadjuvant chemo-radiation therapy for resected rectal cancer is allowed provided it is completed within 4 weeks prior to study entry)
• Less than 6 months from completion of adjuvant chemotherapy to diagnosis or documentation of recurrent cancer
• Palliative radiotherapy to non-target, metastatic lesions will be allowed provided it was completed within 4 weeks prior to study entry.
• Prior surgery or IMP within 4 weeks prior to study entry
• Current treatment within another therapeutic clinical trial.
• Presence of grade ≥2 peripheral neuropathy.
• Known dihydropyrimidine dehydrogenase deficiency or severe hypersensitivity reaction to 5-FU
• Grade ≥2 thrombocytopenia (i.e., platelet count \<75,000/µL), grade 3 neutropenia (i.e., absolute neutrophil count \<1000/µL), or grade 3 non-hematologic adverse event associated with prior adjuvant oxaliplatin and/or 5-FU treatment.
• History of significant bleeding within the past 3 months, including gross haemoptysis or haematuria, or underlying coagulopathy.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrolment, unless affected area has been removed surgically.
• On-going cardiac dysrhythmias of grade ≥2, atrial fibrillation of any grade, or QTc interval to \>450 msec for males and \>470 msec for females.
• Hypertension uncontrolled by medication (\>150/100 mmHg despite optimal medical therapy).
• On-going treatment with therapeutic doses of warfarin (however, low dose warfarin up to 2mg daily for deep vein thrombosis prophylaxis is allowed). Low molecular weight heparin (LMWH) is allowed.
• 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)

Sponsors & Collaborators

• Imperial College London: lead
• Pfizer: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Axitinib

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Charlotte Wyard
• Organization: Imperial College London

c.wyard23@imperial.ac.uk

02033131362

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 21, 2020
• Study Start: September 17, 2012
• Primary Completion: February 22, 2019
• Study Completion: February 22, 2019
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-04

Locations

GB (1)