Single Agent Regorafenib in First-line for Metastatic/Unresectable KIT/PDGFR Wild Type GIST

NCT02638766 | Completed Phase 2

• 1 other identifier: REGISTRI (GEIS 40)
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 17

Brief Summary

Evaluate the treatment with regorafenib in patients with metastatic and/or unresectable KIT/PDGFR wild type GIST in the first line setting.

Conditions

Gastrointestinal Stromal Tumors

Keywords

metastatic; unresectable; KIT/PDGFR wild type GIST

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  the sum of complete responses (CR) + partial responses (PR) + stable disease (SD).

  every 8 weeks during 36 months

Secondary Outcomes (8)

• Progression free survival

  every 8 weeks during 36 months

• Overall survival

  Every 8 weeks during 36 months

• Responses determined by CHOI

  every 8 weeks during 36 months

• Correlation with translational research

  After 36 months of recruitment

• Safety (adverse events following CTCAE v4.03)

  Every 28 days until 30 days after last dose

Study Arms (1)

Unique arm

OTHER

Regorafenib 160mg once a day, frequency: 3 weeks on/1 week off in cycles of 28 days

Drug: regorafenib

Interventions

regorafenib DRUG

Treatment with regorafenib 160mg once a day, 3 weeks on / 1 week off in cycles of 28 days

Also known as: Stivarga

Unique arm

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up.
• Informed Consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient´s routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
• Male or female subjects ≥18 years of age
• Histologically confirmed GIST KIT/PDGFR wild-type, unresectable or metastatic GIST (confirmed by central laboratory). Paraffin-embedded tumor block must be provided by all subjects during screening period.
• Screening of mutations done in exon 11, 9, 13 and 17 in KIT gene and in 12 and 18 exons of PDGFR gene
• Subjects must have at least one measurable lesion according to RECIST v1.1 criteria. A lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of the lesion prior to study enrolment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
• Total Bilirubin ≤ 1.5 x the upper normal limit (UNL). Documented Gilbert Syndrome is allowed if total bilirubin is mildly elevated (≤6mg/dl).
• Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x UNL (≤5xUNL for subjects with liver involvement of GIST)
• Lipase ≤1.5 x UNL
• Serum Creatinine ≤ 1.5 x UNL
• Glomerular filtration rate (GFR) ≥ 30ml/mn/1.73 m2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula.
• International Normalized Ratio (INR) ≤1.5xUNL and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5xUNL. Subjects who are being treated with an anti-coagulant, such as warfarin or heparin, will be allowed to participate provided that no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standards of care.
• Alkaline phosphatase limit ≤ 2.5 x UNL (≤ 5x UNL for subjects with disease involving the liver)

You may not qualify if:

• Prior systemic treatment for GIST BESIDES IMATINIB. Patients that have relapsed after receiving imatinib during adjuvant setting and patients who are on treatment or have been treated with Imatinib as first line of advanced KIT/PDGFRa wild type GIST are eligible.
• Cancer other than GIST within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta (Non Invasive tumor), and Tis (Carcinoma In situ)).
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before the start of study medication.
• Congestive Heart Failure New York Heart Association (NYHA) ≥ class 2.
• Unstable angina (angina symptoms at rest, new-onset angina, ie, within the lasts 3 months prior to entering study) or myocardial infarction (MI) within the past 6 months before the start of study medication.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Uncontrolled hypertension (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90mmHg despite optimal medical management).
• Subjects with pheochromocytoma.
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months from start of study treatment.
• Venous thrombotic events such as deep vein thrombosis within the 3 months before the start of study treatment.
• Ongoing infection \> grade 2 National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03
• Known history of human immunodeficiency virus (HIV) infection.
• Subjects with seizure disorder requiring medication
• Symptomatic metastasis in brain or meningeal tumors.
• History of organ allograft.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead
• Bayer: collaborator

Study Sites (17)

Institute Bergonie

Bordeaux, France

Location

Centre Leon Berard

Lyon, France

Location

Gustave Roussy

Villejuif, France

Location

Fondazione IRCCS Istituto Dei Tumori di Milano

Milan, Italy

Location

Fondazione G Pascale Napoli

Napoli, 80131, Italy

Location

Policlinico Universitario Campus Bio-Medico

Roma, Italy

Location

Istituto di Candiolo - IRCSS

Torino, Italy

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital de Cruces

Barakaldo, 48902, Spain

Location

Hospital Universitario Vall d´hebron

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Virgen de la Macarena

Seville, 41071, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (1)

• Martin-Broto J, Valverde C, Hindi N, Vincenzi B, Martinez-Trufero J, Grignani G, Italiano A, Lavernia J, Vallejo A, Tos PD, Le Loarer F, Gonzalez-Campora R, Ramos R, Hernandez-Jover D, Gutierrez A, Serrano C, Monteagudo M, Leton R, Robledo M, Moura DS, Martin-Ruiz M, Lopez-Guerrero JA, Cruz J, Fernandez-Serra A, Blay JY, Fumagalli E, Martinez-Marin V. REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial. Mol Cancer. 2023 Aug 9;22(1):127. doi: 10.1186/s12943-023-01832-9.

  PMID: 37559050 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors; Neoplasm Metastasis

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Javier Martín-Broto, MD

  GEIS (GRUPO ESPAÑOL DE INVESTIGACION EN SARCOMAS

  STUDY CHAIR

• Virginia Martínez-Marín, MD

  GEIS (GRUPO ESPAÑOL DE INVESTIGACION EN SARCOMAS

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: December 23, 2015
• Study Start: November 1, 2015
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); IT (4); ES (10)