Study Comparing Different Dose Approaches of Induction Treatment of Regorafenib in MCRC

NCT02835924 | Completed Phase 2

• 1 other identifier: TTD-16-01
• Study Type: interventional
• Target: 299
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and tolerability of different dose-escalation approaches of regorafenib in mCRC patients.

Conditions

Metastatic Colorectal Cancer

Keywords

regorafenib; metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with G3/G4 treatment-related AEs in each arm according to CTCAE v4.03 criteria.

  30 months

Secondary Outcomes (7)

• Percentage of total administrated dose over the planned dose accomplished in each arm.

  30 months

• Dose intensity during the whole treatment.

  30 months

• Dose intensity during first two cycles.

  2 months

• Disease control rate (DCR)

  30 months

• Progression-free survival (PFS)

  30 months

Study Arms (3)

Arm A

ACTIVE COMPARATOR

160 mg/day 3w on/1w off

Drug: Regorafenib

Arm B

EXPERIMENTAL

120 mg/day 3w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on

Drug: Regorafenib

Arm C

EXPERIMENTAL

160 mg/day 1w on/1w off 1st cycle; 160 mg/day 3w on/1w off 2nd cycle on

Drug: Regorafenib

Interventions

Regorafenib DRUG

Arm A; Arm B; Arm C

Eligibility Criteria

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

You may qualify if:

• Signed informed consent (IC) obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
• Male or female subjects 18 years of age.
• Life expectancy of at least 3 months.
• Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
• Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion following RECIST criteria v 1.1.
• Subjects with metastatic colorectal cancer (Stage IV).
• Progression during or within 3 months following the last administration of approved standard therapies which must include fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF and an anti-EGFR (if RAS WT)
• Subjects treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
• Subjects who progress more than 6 months after completion of oxaliplatin containing adjuvant treatment must be retreated with oxaliplatin-based therapy to be eligible. Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be allowed into the study
• ECOG Performance Status of 0 or 1(within 14 days prior to the initiation of study treatment)
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements:
• Total bilirubin =1.5 x the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (5 x ULN for subjects with liver involvement of their cancer).
• Alkaline phosphatase limit = 2.5 x ULN (5 x ULN for subjects with liver and/or bone involvement of their cancer).
• Lipase = 1.5 x the ULN.

You may not qualify if:

• Prior treatment with regorafenib.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
• Pregnant or breast-feeding subjects:
• Congestive heart failure = New York Heart Association (NYHA) class 2.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
• Myocardial infarction less than 6 months before start of study drug.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Uncontrolled hypertension. (Systolic blood pressure \> 140 mmHg or diastolic pressure \>90 mmHg despite optimal medical management).
• Arterial or venous thromboembolism within 6 months prior to randomization.
• Pleural effusion or ascites that causes respiratory compromise (CTCAE Grade 2 dyspnea).
• Ongoing infection \> Grade 2 CTCAE v. 4.0.
• Known history of human immunodeficiency virus (HIV) infection.
• Known history of active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
• Subjects with seizure disorder requiring medication.
• History of organ allograft.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Bayer: collaborator

Study Sites (1)

Spanish Cooperative Group for the Treatment of Digestive Tumors

Madrid, 28007, Spain

Location

Related Publications (2)

• Argiles G, Mulet N, Valladares-Ayerbes M, Vieitez JM, Gravalos C, Garcia-Alfonso P, Santos C, Tobena M, Garcia-Paredes B, Benavides M, Cano MT, Loupakis F, Rodriguez-Garrote M, Rivera F, Goldberg RM, Cremolini C, Bennouna J, Ciardiello F, Tabernero JM, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) and UNICANCER GI; The, REARRANGE investigators; Principal investigator; Argiles G, Tabernero J; Steering Committee; Investigators. A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial). Eur J Cancer. 2022 Dec;177:154-163. doi: 10.1016/j.ejca.2022.09.037. Epub 2022 Oct 14.

  PMID: 36335783 DERIVED

• Weinberg BA, Hartley ML, Salem ME. Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 2: Approaches Beyond First-Line Therapy, and Novel Biologic Agents Under Investigation. Oncology (Williston Park). 2017 Jul 15;31(7):573-80.

  PMID: 28712102 DERIVED

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 Officials

• Guillem Argiles

  Hospital Universitary Vall d'Hebron

  STUDY CHAIR

• Josep Mª Tabernero, MD-PhD

  Hospital Universitary Vall d'Hebron

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 18, 2016
• Study Start: July 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2019
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)