Regorafenib in Combination With TAS-102 in Subjects With Metastatic Colorectal Cancer Who Have Progressed After Standard Therapy

NCT03305913 | Completed Phase 1 DMC

• 2 other identifiers: 0116-ASG2016-001968-11
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

0116-ASG REMETY is a multicenter, open-label, non-randomized, dose-escalation Phase I study evaluating the safety and anti-tumor activity of TAS-102 administered in combination with Regorafenib in patients with metastatic colorectal cancer.

Conditions

Pretreated Metastatic Colorectal Cancer

Keywords

mCRC

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Maximum Tolerated Dose (MTD) will be determined by recording dose limiting toxicities (DLT) occurring during the first 2 treatment cycles of each patient in each tested dose level. DLT will be identified by observing frequency and severity of specific adverse events.

  2 months

Secondary Outcomes (4)

• Overall Response Rate (ORR) according to RECIST 1.1 criteria

  approx. 12 months

• Progression-free survival (PFS)

  approx. 12 months

• Overall survival (OS)

  approx. 12 months

• Incidence of Treatment-Emergent Adverse Events

  approx. 12 months

Study Arms (6)

Dose Level 1

EXPERIMENTAL

TAS-102 25 mg/m2 BID (days 1-5 and 8-12) Regorafenib 120 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Dose Level 2

EXPERIMENTAL

TAS-102 35 mg/m2 BID (days 1-5 and 8-12), Regorafenib 120 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Dose Level 3

EXPERIMENTAL

TAS-102 35 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 160 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Dose Level -1a

EXPERIMENTAL

TAS-102 25 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 80 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Dose Level -1b

EXPERIMENTAL

TAS-102 35 mg/m2 BID, (days 1-5 and 8-12) Regorafenib 80 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Dose Level -2a

EXPERIMENTAL

TAS-102 30 mg/m2 BID (or 35 mg/m2 a.m. and 25 mg/m2 p.m.), (days 1-5 and 8-12) Regorafenib 120 mg daily (3 weeks on, 1 week off)

Drug: TAS 102; Drug: Regorafenib

Interventions

TAS 102 DRUG

TAS-102 tablet

Also known as: Lonsurf

Dose Level -1a; Dose Level -1b; Dose Level -2a; Dose Level 1; Dose Level 2; Dose Level 3

Regorafenib DRUG

Regorafenib tablet

Also known as: Stivarga

Dose Level -1a; Dose Level -1b; Dose Level -2a; Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry
• Histological or cytological documentation of adenocarcinoma of the colorectal region (CRC)
• Metastatic disease not amenable to surgical resection with curative intent
• Study treatment must constitute 3rd-line treatment for metastatic disease. Prior treatment lines must encompass at least one fluoropyrimidine-based chemotherapy, an anti-VEGF and, in case of RAS wildtype tumors, an anti-EGFR treatment.
• Patients treated with oxaliplatin in an adjuvant setting need to have progressed during or within 6 months of completion of adjuvant therapy to be counted as prior treatment line. Note: Neoadjuvant, perioperative or adjuvant regimens with progression more than 6 months after completion are not considered as prior treatment line for metastatic disease.
• Measurable disease, defined as at least one unidimensional measurable lesion on a CT scan as defined by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status \<2 and life expectancy of at least 3 months
• Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days prior to study treatment initiation:
• Absolute neutrophil count (ANC) ≥1,500/mm3
• Platelets ≥100,000/mm3
• Hemoglobin ≥9.0 g/dL
• Serum creatinine ≤1.5 x upper limit of normal (ULN)
• Glomerular filtration rate (GFR) ≥30 mL/min/1.73m2
• AST and ALT ≤2.5 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer)

You may not qualify if:

• Prior treatment with Regorafenib, or any other tyrosine kinase inhibitor for the treatment of malignancy
• Prior treatment with TAS-102
• Known history of/or concomitant malignancy other than mCRC likely to affect life expectancy in the judgment of the investigator
• History of Gilbert's syndrome
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days and last chemotherapy \<21 days prior to first dose of treatment
• Radiotherapy within 4 weeks prior to first dose of treatment
• Active cardiac disease including any of the following:
• Congestive heart failure (New York Heart Association NYHA) ≥Class 2
• Unstable angina (angina symptoms at rest), new-onset angina (within the last 3 months).
• Myocardial infarction less than 6 months before start of Day 1 of treatment.
• 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 thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before start of treatment
• Known history of human immunodeficiency virus (HIV) infection
• Chronic hepatitis B or C infection (If hepatitis status can not be obtained from medical records re-testing is required.)

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Institut für Klinisch-Onkologische Forschung (IKF) am Krankenhaus Nordwest GmbH: collaborator
• Bayer: collaborator

Study Sites (1)

Universitätsmedizin Mainz, I.Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Related Publications (1)

• Moehler M, Michel M, Stein A, Trojan J, Marquardt J, Tintelnot J, Waidmann O, Weinmann A, Woerns MA, Schroeder H, Maenz M, Foerster F. A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer. Future Oncol. 2021 Sep;17(25):3309-3319. doi: 10.2217/fon-2021-0278. Epub 2021 May 17.

  PMID: 33993741 DERIVED

MeSH Terms

Interventions

trifluridine tipiracil drug combination; regorafenib

Study Officials

• Markus Möhler, Prof. Dr.

  Universitätsmedizin Mainz, I.Medizinische Klinik und Poliklinik, Langenbeckstraße 1, 55131 Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: According to the standard 3+3 dose finding strategy, a safety assessment will be performed after the test of each dose level (patient cohorts of n=3) and the frequency of DLTs determined. Based on the results the dose for the consecutive patient cohort will either be escalated (0/3 DLTs), repeated (1/3 DLTs) or deescalated (\>1/3 DLTs).

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: October 10, 2017
• Study Start: July 31, 2017
• Primary Completion: October 31, 2018
• Study Completion: April 26, 2019
• Last Updated: March 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)