Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Regorafenib Monotherapy

NCT03010722 | Completed DMC

• 1 other identifier: 4164
• Study Type: observational
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single centre prospective biological translational research study involving the collection of tumour tissue, blood samples and clinical data from patients being treated with regorafenib for metastatic Colorectal Cancer (mCRC) at the Royal Marsden Hospital. Patients will be eligible for the study if they have a histological diagnosis of CRC, are refractory to standard available therapies with palliative intent for mCRC, have received prior treatment with at least one anti-VEGF antibody and chemotherapy drugs including fluorouracil (5FU) or capecitabine, oxaliplatin and irinotecan, and patients have RAS mutant tumours.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• disease control rate (DCR), measured in months

  DCR will be defined as complete response (CR)/partial response (PR)/ stable disease (SD) using RECIST v1.1. Chi2 or Fisher's exact tests will be employed to explore whether there is an association between low or high mutations and DCR. Logistic regression will be employed to produce odds ratios (ORs) and 95% confidence intervals (CIs).

  12 months

Secondary Outcomes (3)

• progression free survival (PFS), measured in months

  12 months

• overall survival (OS), measured in months

  12 months

• Median values of volume transfer constant (Ktrans) and enhancing fraction (EF) and their product KEF (product of summarised median values of Ktrans x EF/100) will be compared at baseline and on day 15

  15 days

Study Arms (1)

Regorafenib

160 mg orally (po) od for 3 weeks of every 4-week cycle All patients will be required to have pre-treatment dynamic contrast enhance computed tomography (DECT) scan pre-treatment and at 8 weeks. Suitable patients will also be required to have dynamic contrast enhanced magnetic resonance imaging (DEC-MRI) and diffusion weighted (DW)-MRI, pre-treatment and at 2 weeks. All patients will also be required to have an Ultrasound (USS) or CT-guided biopsy of suitable metastatic lesion.

Drug: Regorafenib

Interventions

Regorafenib DRUG

Patients meeting all of the inclusion criteria and none of the exclusion criteria will receive regorafenib 160 mg orally (po) od for 3 weeks of every 4-week cycle. Each cycle will comprise 3 weeks of treatment followed by 1 week without treatment, hereafter described as "3 weeks on/1 week off". Each 160-mg dose will include four regorafenib 40-mg tablets.

Also known as: Stivarga

Regorafenib

Eligibility Criteria

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

Study Population

Patients will be selected from the clinics and multi-disciplinary meetings, so long that they meet all the inclusion criteria and no exclusion criteria.

You may qualify if:

• Patients with RAS mutant (MT) metastatic colorectal cancer (mCRC) who have been at least once treated with available therapies including fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan and an anti-angiogenic agent, except for patients who have not been treated with oxaliplatin due to previous documented peripheral neuropathy in an adjuvant setting or in those patients where disease has progressed within a short time from receiving adjuvant treatment (\<12 months).
• Eligible to receive regorafenib within the context of PROSPECT-R trial at the Royal Marsden Hospital

You may not qualify if:

• A patient must NOT
• have had prior treatment with regorafenib or any other VEGF-targeting kinase inhibitor
• have had previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (Noninvasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)\].
• Patients that are participating in another clinical trial involving an investigational medicinal product, unless it is more than 14 days after they have ceased the investigational medicinal product
• Patients that are participating in another research study involving tumour tissue biopsies planned to take place during the time that the patient is participating in this study
• Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
• If female and of childbearing potential, be engaged in breast feeding
• Be unable to swallow oral tablets (crushing of study treatment tablets is not allowed)
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
• Ongoing infection \> Grade 2 NCI Common Toxicity Criterial for Adverse Effects (CTCAE).
• Uncontrolled hypertension (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg) despite optimal medical management
• Have congestive heart failure classified as New York Heart Association Class 2 or higher
• Have had unstable angina (angina symptoms at rest) or new-onset angina \< 3 months prior to screening
• Have had a myocardial infarction \< 6 months prior to initiation of study treatment

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Bayer: collaborator

Study Sites (1)

The Royal Marsden NHS Foundation Trust London and Surrey

Carshalton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Rata M, Khan K, Collins DJ, Koh DM, Tunariu N, Bali MA, d'Arcy J, Winfield JM, Picchia S, Valeri N, Chau I, Cunningham D, Fassan M, Leach MO, Orton MR. DCE-MRI is more sensitive than IVIM-DWI for assessing anti-angiogenic treatment-induced changes in colorectal liver metastases. Cancer Imaging. 2021 Dec 19;21(1):67. doi: 10.1186/s40644-021-00436-0.

  PMID: 34924031 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Tissue and plasma samples will be retained for a maximum period of 20 years, according to UK regulatory approval policy and study protocol.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 5, 2017
• Study Start: January 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: July 1, 2017
• Last Updated: May 3, 2021

Record last verified: 2017-01

Locations

GB (1)