Ph II CABOGIST in GIST

NCT02216578 | Completed Phase 2 DMC

• 2 other identifiers: EORTC-13172014-000501-13
• Study Type: interventional
• Target: 51
• Locations: 6 countries
• Sites: 11

Brief Summary

The study is a multi-center, multi-national, open label, single arm Phase II study of single-agent cabozantinib. The objective of the study is to assess the safety and activity of cabozantinib in patients with metastatic GIST who have previously progressed on imatinib and sunitinib and have not been exposed yet to other KIT- or PDGFR-directed tyrosine kinase inhibitors. Patient will receive cabozantinib until they experience no further benefit from the treatment, becoming intolerant to the drug or wishing to discontinue the treatment. Treatment beyond RECIST 1.1 progression is allowed in patients deriving clinical benefit upon investigator's discretion, provided no other criteria for treatment withdrawal are met.

Conditions

Metastatic Gastrointestinal Stromal Tumor

Keywords

tyrosine kinase inhibitor; progressed; (GIST)

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  at 12 weeks

Secondary Outcomes (6)

• Progression Free Survival (PFS) (RECIST 1.1)

  at 12 weeks

• Overall survival (OS)

  at 12 weeks

• Objective response rate (ORR), defined as Complete Response (CR)+ Partial Response (PR) (RECIST 1.1)

  3 years

• Clinical benefit rate (CBR) defined as CR+PR+ SD (Stable Disease) (RECIST 1.1)

  3 years

• Time to treatment failure (TTF)

  3 years

Other Outcomes (2)

• mutational subtypes of GIST

  3 years

• circulating plasma DNA

  3 years

Study Arms (1)

cabozantinib

EXPERIMENTAL

cabozantinib 60 mg oral daily

Drug: cabozantinib

Interventions

cabozantinib DRUG

Oral

cabozantinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of GIST that is metastatic. Patients with the primary tumor still in place are excluded from the trial, due to the risk for intestinal perforation reported for cabozantinib.
• Presence of at least one non-previously irradiated, measurable metastatic lesion as defined by RECIST 1.1.
• Archival tumor tissue available from primary tumor or metastatic site (10 unstained slides with archived tumor tissue of 10 micrometer thickness and two hematoxylin and eosin (H\&E) stained slides) for central mutational analysis; Note: slides are preferred material but if not available blocks are accepted
• Failure on prior therapy with
• Interval from prior TKI therapy to the first dose of cabozantinib should be at least 14 days
• Radiological progression on imatinib during neoadjuvant, adjuvant or palliative treatment of GIST or within 3 months after completing adjuvant treatment with imatinib AND radiological progression on sunitinib for the treatment of advanced GIST
• Note: progression is assessed by local radiologist/oncologist without central confirmation of pre-baseline progression.
• Agreement of the patient to allow sequential sampling of circulating cell-free DNA for central mutational analysis is mandatory.
• Male or female patient ≥ 18 years of age
• ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0-1
• Adequate bone marrow and organ function as defined by the following laboratory values assessed within ≤ 14 days prior to receiving the first dose of study treatment:
• ANC (Absolute Count Neutrophils) ≥ 1.5 x 10exp9/L (no prophylactic administration of G-CSF (Granulocyte Colony Stimulating Factor) or GM (Granulocyte Macrophage) -CSF allowed).
• Platelet count ≥ 100 x 10exp9/L or x 10exp3/μL (transfusion allowed).
• Hemoglobin ≥ 9.0 g/dL or 5.6 mmol/L (transfusion and erythropoietin allowed).
• Prothrombin time (PT)/ INR (International Normalized Ratio) or partial thromboplastin time (PTT) test \< 1.3 X ULN within 7 days before the first dose of study treatment; Note: patients requiring concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel) are not eligible. Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic LMWH (Low Molecular Weight Heparin) are permitted;

You may not qualify if:

• evidence of tumor invading the gastrointestinal tract (esophagus, stomach, small or large bowel, rectum or anus) within 28 days prior to the first dose of cabozantinib.
• current evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib.
• radiographic presence of a cavitating pulmonary lesion within 28 days prior to the first dose of cabozantinib. patient with tumor in contact with, invading or encasing a major blood vessel
• other prior tyrosine kinase inhibitors for the treatment of advanced GIST.
• other investigational agents within 28 days before the first dose of study treatment;
• specific contraindications for treatment with cabozantinib (e.g. no known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to cabozantinib).
• poorly controlled hypertension defined at baseline as blood pressure (BP) \>150/90 mmHg.
• cerebrovascular accident, no transient ischemic attack and no pulmonary embolism in the past 6 months.
• gastrointestinal disorders associated with a high risk of perforation or fistula formation within 28 days before the first dose of study treatment, including the following:
• Known intra-abdominal tumor/metastases invading gastrointestinal mucosa.
• Active peptic ulcer disease.
• Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis.
• Malabsorption syndrome.
• One of the following within 6 months before the first dose of study treatment:
• Clinically significant gastrointestinal bleeding.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (11)

U.Z. Leuven - Campus Gasthuisberg (147)

Leuven, Belgium

Location

University Hospital Motol (1905)

Prague, Czechia

Location

Institut Bergonie (228)

Bordeaux, France

Location

Centre Leon Berard (227)

Lyon, France

Location

Gustave Roussy (225)

Villejuif, France

Location

UniversitaetsMedizin Mannheim (527)

Mannheim, Germany

Location

Military Hospital - State Health Centre (3769)

Budapest, Hungary

Location

Clatterbridge Centre for Oncology NHS Trust - Clatterbridge Cancer Centre NHS Foundation Trust (659)

Bebington, United Kingdom

Location

Royal Marsden Hospital - Chelsea, London (613)

Chelsea, United Kingdom

Location

University College London Hospitals NHS Foundation Trust - University College Hospital (622)

London, United Kingdom

Location

The Christie NHS Foundation Trust (610)

Manchester, United Kingdom

Location

Related Publications (2)

• Kyriazoglou A, Jespers P, Vandecavaye V, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Zaffaroni F, Litiere S, Nzokirantevye A, Schoffski P. Exploratory analysis of tumor imaging in a Phase 2 trial with cabozantinib in gastrointestinal stromal tumor: lessons learned from study EORTC STBSG 1317 'CaboGIST'. Acta Oncol. 2022 Jun;61(6):663-668. doi: 10.1080/0284186X.2022.2068967. Epub 2022 Apr 28.

  PMID: 35481400 DERIVED

• Schoffski P, Mir O, Kasper B, Papai Z, Blay JY, Italiano A, Benson C, Kopeckova K, Ali N, Dileo P, LeCesne A, Menge F, Cousin S, Wardelmann E, Wozniak A, Marreaud S, Litiere S, Zaffaroni F, Nzokirantevye A, Vanden Bempt I, Gelderblom H. Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'. Eur J Cancer. 2020 Jul;134:62-74. doi: 10.1016/j.ejca.2020.04.021. Epub 2020 May 26.

  PMID: 32470848 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

cabozantinib

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

Study Officials

• Patrick Schöffski, MD

  U.Z. Leuven -Campus Gasthuisberg, Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 31, 2014
• First Posted: August 15, 2014
• Study Start: February 2, 2017
• Primary Completion: May 20, 2019
• Study Completion: February 23, 2021
• Last Updated: July 15, 2021

Record last verified: 2021-07

Locations

HU (1); FR (3); GB (4); BE (1); DE (1); CZ (1)