Regorafenib and XELOX as 2nd Line Treatment in Metastatic Colorectal Cancer

NCT04008511 | Unknown Phase 1 DMC

• 2 other identifiers: CLOG1901IMPACT 20872
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is an interventional, randomized open-label, parallel-group, multicenter, dose escalation phase Ib/II study, to investigate the combination of Regorafenib and XELOX as 2nd line treatment in mCRC patients.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer; Regorafenib; Second line; XELOX

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  The MTD is defined as the highest dose that can be given so that toxicity probability is below the target toxicity PT=30%.

  6 weeks

• Progression-free survival (PFS)

  PFS is defined as the time (days) from start of study treatment to date of first observed disease progression (investigator's radiological or clinical assessment) or death due to any cause, if death occurs before progression is documented.

  1 year

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Safety and tolerability

  3 years

Secondary Outcomes (2)

• Disease control rate (DCR)

  3 years

• Overall response rate (ORR)

  3 years

Study Arms (3)

Phase Ib: Regorafenib plus XELOX

EXPERIMENTAL

Phase Ib followed a Modified toxicity probability interval (mTPI) design to determine the maximum administered dose (MAD), there are 3 dose levels, and the dose level started from Group A: Group A: Regorafenib 120mg + XELOX; Group B: Regorafenib 160mg + XELOX; Group C: Regorafenib 80mg + XELOX. (Regorafenib qd po for 14 days, every 3 weeks; XELOX: Oxaliplatin 130 mg/m2 IV, day 1, Capecitabine 1000 mg/m2 bid po for 14 days)

Drug: Regorafenib; Drug: Capecitabine; Drug: Oxaliplatin

Phase II: Regorafenib plus XELOX

EXPERIMENTAL

Regorafenib MAD qd po for 14 days, every 3 weeks, Oxaliplatin 130 mg/m2 IV on day 1, Capecitabine 1000 mg/m2 bid po for 14 days.

Drug: Regorafenib; Drug: Capecitabine; Drug: Oxaliplatin

Phase II: XELOX

ACTIVE COMPARATOR

Oxaliplatin 130 mg/m2 IV on day 1, Capecitabine 1000 mg/m2 bid po for 14 days.

Drug: Capecitabine; Drug: Oxaliplatin

Interventions

Regorafenib DRUG

Phase Ib Group A: Regorafenib 120mg + XELOX; Group B: Regorafenib 160mg + XELOX; Group C: Regorafenib 80mg + XELOX.

Also known as: Stivarga

Phase Ib: Regorafenib plus XELOX

Capecitabine DRUG

Capecitabine 1000 mg/m2 bid po for 14 days.

Also known as: Xeloda

Phase II: Regorafenib plus XELOX; Phase II: XELOX; Phase Ib: Regorafenib plus XELOX

Oxaliplatin DRUG

Oxaliplatin 130mg/m2, day 1, every 3 weeks

Also known as: ELOXATIN®

Phase II: Regorafenib plus XELOX; Phase II: XELOX; Phase Ib: Regorafenib plus XELOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a consent form
• Age\> 18 years \<75 years
• Pathological diagnosis as colorectal adenocarcinoma
• Recurrence or metastatic disease
• Metastatic colorectal cancer with disease progression after 1st line treatment by 5-Fu and Irinotecan
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
• ECOG score 0-1 points
• Life expectancy ≥3 months
• Can provide more than 10 paraffin sections of tumor tissue
• End of radiotherapy without or with non-targeted lesions\> 4 weeks (only for use outside of the test site)
• At least one measurable lesion (according to RECIST 1.1)
• Previously treated radiotherapy lesions cannot be considered as target lesions, unless the radiotherapy lesions clear progress.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases ≤ 5 times ULN
• Serum albumin ≥ 3.0g / dL
• Serum alkaline phosphatase (AKP) ≤2.5 times ULN

You may not qualify if:

• Received oxaliplatin and capecitabine in the 1st line treatment
• Cannot be orally administered
• Subjects with brain metastases and / or cancerous meningitis.
• Surgical treatment was performed within 4 weeks before enrollment (excluding diagnostic biopsies)
• Non-healing wound, non-healing ulcer, or non-healing bone fracture
• Patients with evidence or history of any bleeding diathesis, irrespective of severity
• Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months 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)
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2
• Uncontrolled cardiac arrhythmias
• Ongoing infection \> Grade 2 NCI CTCAE
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
• Anti-tumor cytotoxic drug therapy, biologic medication (eg, monoclonal antibody), immunotherapy (eg, interleukin 2 or interferon), or other investigational drug therapy within 4 weeks prior to enrollment
• Subjects with active tuberculosis (TB) who are on anti-TB treatment or who have received anti-TB treatment within 1 year prior to screening

Sponsors & Collaborators

• China Medical University, China: lead
• Liaoning Cancer Hospital & Institute: collaborator
• The First People's Hospital of Jingzhou: collaborator

Study Sites (1)

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Capecitabine; Oxaliplatin

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Yunpeng Liu, M.D.,Ph.D.

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunpeng Liu, M.D.,Ph.D.

CONTACT

86-24-83282312; cmu_trial@163.com

Xiujuan Qu, M.D.,Ph.D.

CONTACT

86-24-83282312; cmuquxiujuan@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: July 1, 2019
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: July 5, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)