Regorafenib Combined With Irinotecan as Second-line in Patients With Metastatic Gastro-oesophageal Adenocarcinomas

NCT03722108 | Terminated Phase 1 DMC

• 2 other identifiers: UC-0110/18072018-002374-46
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 27

Brief Summary

Trial evaluating the efficacy of regorafenib combined with irinotecan compared to irinotecan alone in second-line treatment of patients with metastatic gastro-oesophageal adenocarcinomas.

Conditions

Adenocarcinoma of the Stomach; Adenocarcinoma of the Gastroesophageal Junction

Keywords

adenocarcinoma; gastro-oesophageal; regorafenib

Outcome Measures

Primary Outcomes (1)

• To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of overall survival (OS)

  Time duration from randomisation to time of death of any cause. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up.

  expected duration of 10 months from randomisation

Secondary Outcomes (8)

• To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the overall survival rate

  6 and 12 months from randomisation

• To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival (PFS)

  expected duration of 6 months from randomisation

• To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival rate

  6 and 12 months from randomisation

• To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the disease control rate (DCR)

  expected duration of 6 months from randomisation

• To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the objective response rate (ORR)

  expected duration of 6 months from randomisation

Study Arms (2)

Regorafenib and Irinotecan

EXPERIMENTAL

Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle combined with regorafenib 160 mg daily on Day2-8 and D16-22 of a 4 week cycle administered until progression of disease or unacceptable toxicity.

Combination Product: Regorafenib and Irinotecan

Irinotecan

ACTIVE COMPARATOR

Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle administered until progression of disease or unacceptable toxicity

Drug: Irinotecan

Interventions

Regorafenib and Irinotecan COMBINATION_PRODUCT

Irinotecan (180 mg/m² on D1 and D15 of a 4-week cycle) combined with regorafenib (160 mg daily on D2-8 and D16-22 of a 4-week cycle) administered until progression of disease or unacceptable toxicity

Also known as: STIVARGA, CAMPTO

Regorafenib and Irinotecan

Irinotecan DRUG

Irinotecan (180 mg/m² on D1 and D15 of a 4-week cycle) administered until progression of disease or unacceptable toxicity

Also known as: CAMPTO

Irinotecan

Eligibility Criteria

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

You may qualify if:

• Patient must have signed a written informed consent form prior to any study specific procedures
• Patients aged ≥18 years old
• Histologically confirmed diagnosis of gastro-oesophageal adenocarcinomas: gastroesophageal junction (Siewert II and III) and gastric adenocarcinomas
• Asymptomatic primary tumour
• Metastatic disease
• At least one target lesion (according to RECIST v1.1):
• Unidimensionally measurable on cross-sectional imaging
• In an area not previously irradiated
• Disease progression after a fluoropyrimidine and platinum agent-based chemotherapy (5-fluorouracil or 5-fluorouracil prodrugs combined with cisplatin or oxaliplatin). For example, docetaxel combined with FOLFOX, PD-L1/PD-1 inhibitors combined with FOLFOX, LV5-FU2-cisplatin or 5-fluorouracil-cisplatin are acceptable prior therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy \>3 months
• Amylase ≤1.5 x upper limit of normal (ULN) and lipase ≤1.5 x ULN
• Adequate liver function:
• Total bilirubin ≤1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN for patients with liver metastasis)

You may not qualify if:

• Symptomatic brain metastases or carcinomatous meningitis
• Bone-only metastasis
• Known and documented UGT1A1 deficiency
• History of Gilbert's syndrome
• Previous or concurrent cancer with a distinct primary site, other than gastro-oesophageal cancer, within 5 years prior to randomisation (except for curatively treated cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumours)
• Persistent proteinuria \>3.5 g/24 h measured by urine protein-creatinine ratio from a random urine sample (grade ≥3, NCI-CTCAE v 5.0)
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients
• Non-healing wound, non-healing ulcer, or non-healing bone fracture
• Patients with evidence or history of any bleeding diathesis, irrespective of severity
• Any haemorrhage or bleeding event grade ≥3 (NCI-CTCAE v.5.0) within 4 weeks before starting of the study treatment
• 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 starting the study treatment (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
• Uncontrolled hypertension (systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg) despite optimal medical management. Congestive heart failure: New York Heart Association (NYHA) ≥ class 2
• Unstable angina (angina symptoms at rest), new-onset angina (that started within the last 3 months)
• Myocardial infarction less than 6 months before starting the study treatment
• Uncontrolled cardiac arrhythmias

Sponsors & Collaborators

• UNICANCER: lead
• Bayer: collaborator

Study Sites (27)

Institut de Cancérologie de l'Ouest-Paul Papin

Angers, France

Location

Hôpital Morvan

Brest, France

Location

Clinique de Flandre

Coudekerque-Branche, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Hôpital Franco-Britannique

Levallois-Perret, France

Location

Hopital Claude Huriez - CHU Lille

Lille, France

Location

CHU Dupuytren

Limoges, France

Location

Centre Léon Bérard

Lyon, France

Location

Hopital de la Timone

Marseille, France

Location

Institut Paoli Calmette

Marseille, France

Location

Institut du Cancer Montpellier

Montpellier, 34298, France

Location

Centre de Cancérologie du Grand Montpellier

Montpellier, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

GH Diaconesses Croix Saint-Simon

Paris, France

Location

CH Saint Jean

Perpignan, France

Location

CHU de Poitiers

Poitiers, 86000, France

Location

CH Annecy Genevois

Pringy, France

Location

Institut Jean Godinot

Reims, 51100, France

Location

Hopital Robert Debre

Reims, France

Location

Hopital Charles Nicolle

Rouen, France

Location

CHP Saint Grégoire

Saint-Grégoire, France

Location

Institut de Cancérologie de l'Ouest-René Gauducheau

Saint-Herblain, France

Location

CH Saint Malo

St-Malo, France

Location

Centre Paul Strass

Strasbourg, France

Location

CHRU Tours

Tours, France

Location

CHU Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

regorafenib; Irinotecan

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Emmanuelle SAMALIN-SCALZI, MD

  Institut du Cancer Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: October 26, 2018
• Study Start: February 7, 2019
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: October 16, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (27)