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Metastatic Gastrointestinal Stromal TumorPhase 2NCT02216578

Ph II CABOGIST in GIST

A Phase 2 study testing cabozantinib in people with Metastatic Gastrointestinal Stromal Tumor, run by European Organisation for Research and Treatment of Cancer - EORTC at 11 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
11 sitesin 6 countries
Study dates
2 Feb 2017to 23 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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;
  • Potassium, calcium, magnesium and phosphorous within normal limits of the institution or corrected to within normal limits prior to the first dose of study medication.
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min or GFR >30 mL/min (as assessed per local standard).
  • Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with Gilbert's syndrome).
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within ≤ 3.0 x ULN.
  • Serum albumin ≥ 2.8 g/dL.
  • Serum lipase < 2 x ULN and no radiologic or clinical evidence of pancreatitis
  • Urine protein/creatinine ratio (UPCR) ≤ 1.
  • Clinically normal cardiac function based on the institutional lower limit of normal for left ventricular ejection fraction as assessed either by multi-gated acquisition scan or cardiac ultrasound, 12 lead ECG without clinically relevant abnormalities (stable atrial fibrillation allowed), no history of congenital long QT syndrome, no prolongation of corrected QT interval (QTcF) > 500 msec according to Fridericia's formula), and no history of any one of the following cardiovascular conditions within the past 6 months:
  • Cardiac angioplasty or stenting.
  • Myocardial infarction.
  • Unstable angina.
  • Coronary artery bypass graft surgery.
  • Clinically significant cardiac arrhythmias
  • Symptomatic peripheral vascular disease.
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA).
  • Patients must be able to swallow and retain oral film-coated tablets.
  • Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically non significant and/or stable on supportive therapy;
  • Prior surgery:
  • Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment is permitted.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
  • Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 4 months after the last study treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Before patient registration, written informed consent must be given according to ICH (International Conference on Harmonisation)/GCP (Good clinical Practice), and national/local regulations.

Who cannot join

  • 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).
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  • 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.
  • Abdominal fistula.
  • Gastrointestinal perforation.
  • Bowel obstruction.
  • Gastric outlet obstruction.
  • Intra-abdominal abscess (complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 6 months before the first dose of study treatment).
  • other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy;
  • evidence of significant active bleeding (including GI bleeding) or bleeding diathesis within 6 months before the first dose of study treatment.
  • hemoptysis ≥ 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment.
  • signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.
  • Note: patient with a prior history of hemoptysis associated with metastatic disease must have a bronchoscopy to rule out endobronchial lesions. A patient with an endobronchial tumor lesion is not eligible for the study.
  • Prior surgery:
  • prior major surgery or trauma within 12 weeks prior to first dose of study drug and/or presence of any non-healing wound, fracture or ulcer. Complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment.
  • Patients with clinically relevant ongoing complications from prior surgery;
  • Following clinically significant disorders such as:
  • active infection requiring systemic treatment within 28 days before the first dose of study treatment;
  • history of organ transplant;
  • concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment.
  • history of other malignancy in the past 5 years with the exception of treated carcinoma in situ of the cervix and non-metastatic, non-melanoma skin cancer. Patients with desmoid fibromatosis or neurofibromas, which can be associated with GIST, are allowed to enter the trial, under the provision that they do have a measurable GIST lesion that can be distinguished from the other lesions.
  • Patients requiring chronic concomitant treatment with strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort)
  • Lactating females

Trial locations and contacts

11 sites in 6 countries.

11 sites in 6 countries

United Kingdom4 sites

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

    Bebington

  • Royal Marsden Hospital - Chelsea, London (613)

    Chelsea

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

    London

  • The Christie NHS Foundation Trust (610)

    Manchester

Other trials in United Kingdom

France3 sites

  • Institut Bergonie (228)

    Bordeaux

  • Centre Leon Berard (227)

    Lyon

  • Gustave Roussy (225)

    Villejuif

Other trials in France

Belgium1 site

  • U.Z. Leuven - Campus Gasthuisberg (147)

    Leuven

Other trials in Belgium

Czechia1 site

  • University Hospital Motol (1905)

    Prague

Other trials in Czechia

Germany1 site

  • UniversitaetsMedizin Mannheim (527)

    Mannheim

Other trials in Germany

Hungary1 site

  • Military Hospital - State Health Centre (3769)

    Budapest

Other trials in Hungary

About this study

Official title: Phase II Study of Cabozantinib in Patients With Gastrointestinal Stromal Tumor (GIST) Who Progressed During Neoadjuvant, Adjuvant or Palliative Therapy With Imatinib and Sunitinib

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.

Being tested
cabozantinib
Keywords
tyrosine kinase inhibitor, progressed, (GIST)
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cabozantinibDrug

    Oral

Study groups in NCT02216578
Study groupRoleWhat they receive
cabozantinibExperimentalcabozantinib 60 mg oral daily
Receives: Drug: cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS)

    Measured: at 12 weeks

Secondary outcomes (6)

  1. Progression Free Survival (PFS) (RECIST 1.1)

    assessed with independent central review of radiological images

    Measured: at 12 weeks

  2. Overall survival (OS)

    Measured: at 12 weeks

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

    assessed with independent central review of radiological images

    Measured: 3 years

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

    assessed with independent central review of radiological images.

    Measured: 3 years

  5. Time to treatment failure (TTF)

    Time to treatment failure (TTF) defined as treatment beyond progression is allowed by the protocol at the discretion of the treating physician)

    Measured: 3 years

  6. Occurence of adverse events

    Safety will be graded according to the Common Terminology Criteria (CTC) for Adverse Events (AE), CTC-AE version 4.0

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2014 (estimated)
  2. Study start2 Feb 2017
  3. Primary completion20 May 2019
  4. Study completion23 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02216578
Sponsor's protocol ID
EORTC-1317
Other IDs
2014-000501-13, 2014
Status last verified
Jul 2021
First submitted
31 Jul 2014
Last updated
15 Jul 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 35481400

  • 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.

    PubMed 32470848

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cabozantinib in people with Metastatic Gastrointestinal Stromal Tumor, run by European Organisation for Research and Treatment of Cancer - EORTC at 11 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United Kingdom, France, Belgium, Czechia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: at 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02216578, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.

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