AzTrials
AzTrials

Maximum Tolerated DosePhase 1/2SeliGISTNCT04138381

Selinexor as Single Agent and With Imatinib in Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (SeliGIST)

A Phase 1/2 study testing Selinexor and Imatinib in people with Maximum Tolerated Dose and GIST, run by Grupo Espanol de Investigacion en Sarcomas at 6 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This is a single-arm, two cohort, open label phase I/II clinical trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Selinexor and Imatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
6 sitesSpain
Study dates
16 Aug 2019to 16 Apr 2023
Phase
Phase 1/2
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

  • Age ≥18 years at the time of study entry.
  • Histologically confirmed metastatic and/or unresectable GIST. Patients must demonstrate prior failure to at least imatinib. Any number of previous therapies for GIST is allowed.
  • Failure of imatinib is defined as disease progression after ≥ 6 months of treatment with imatinib for advanced/metastatic disease. Exception to this rule is GIST patients with documented KIT or PDGFRA mutations.
  • Measurable disease per modified RECIST 1.1.
  • ECOG performance status 0 to 2.
  • Adequate hematopoietic function (within 7 days prior to enrollment):
Show all 19Show fewer
  • Hemoglobin ≥ 9.0 g/dL (90 g/L).
  • Absolute neutrophil count ≥ 1000/mm3.
  • Platelets ≥ 100,000 /mm3. Patients must have at least a 2-week interval from the last red blood cell (RBC) transfusion and/or growth factor support prior to the Screening hemoglobin and neutrophil assessment. However, patients may receive RBC, growth factor support, and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
  • Adequate organ function (within 7 days prior to enrollment):
  • Alanine aminotransferanse (ALT) and aspartate aminotransferanse (AST)
  • ≤2.5 x upper limit of normal (ULN), or ≤ 5.0 x ULN if liver metastases are present.
  • Alkaline phosphatase (ALP) limit < 2.5 x ULN or ≤ 5.0 x ULN if liver metastases are present.
  • Total serum bilirubin ≤ 2 x ULN. Patients with Gilbert's syndrome must have a total bilirubin of < 3 × ULN.
  • Adequate renal function: estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault
  • Patients must be able to swallow oral medication and no malabsorption condition.
  • Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug.
  • Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Cohort A: Intolerance to first-line treatment imatinib 400mg daily.
  • Use of any approved tyrosine kinase inhibitors or investigational agents within 1 week or 5 half-lives of the agent, whichever is shorter, prior to receiving study drugs.
  • Participants who have had radiotherapy within 4 weeks prior to study entry.
  • Major surgery or significant traumatic injury within 4 weeks prior to study entry.
  • Presence of symptomatic or uncontrolled brain or central nervous system metastases.
  • Known or suspected allergy or hypersensitivity to the selinexor, imatinib or any of its components.
Show all 15Show fewer
  • Patient has a history of another primary malignancy that has been diagnosed or required therapy within 1 year prior to the first dose of study drug (The following are exempt from the 1-year limit: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site.)
  • Unstable cardiovascular function: • Symptomatic ischemia, or • Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or • Congestive heart failure (CHF) NYHA Class ≥ 3, or • Myocardial infarction (MI) within 3 months. • Left ventricular ejection fraction < 40 %. • Hypertension > 140 mm Hg systolic or > 90 mm Hg diastolic with or without antihypertensive therapy.
  • Ongoing infection > Grade 2.
  • Patients with any seizure disorder requiring medication.
  • HIV-positive individuals on combination antiretroviral.
  • Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy.
  • Serious psychiatric or medical conditions that could interfere with treatment.
  • Pregnant or lactating females.
  • Strong CYP3A4 inhibitors (e.g. clarithromycin, indinavir, itraconazole, ketoconazole , nefazodone , nelfinavir , posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) within 28 days or 5 drug half-lives (if drug half-life in patients is known), whichever is longer, before start of study treatment.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Spain6 sites

  • H Vall d'Hebrón

    Barcelona, Catalonia, 08035

  • Hospital La Paz

    Madrid, 28046

  • Hospital Virgen de la Arrixaca

    Murcia, 30120

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife, Canary Islands, 238320

  • Hospital Virgen del Rocio

    Seville, Andalusia, 41013

  • Hospital Miguel Servet

    Zaragoza, Zaragoza, Aragón, 50009

Other trials in Spain

About this study

Official title: A Multicenter, Phase Ib/II Trial of Selinexor as a Single Agent and in Combination With Imatinib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GISTs)

This is a single-arm, two cohort, open label phase I/II clinical trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of:

  • Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by an expansion phase (II) testing for safety and preliminary evidence of antitumor activity
  • Cohort B: single-agent, fixed selinexor dose in the same target population
Read the detailed description

Clinical Study Objectives:

Primary clinical study objective

Cohort A:

1.- To determine the maximum tolerated dose (MTD) and recommended phase II doses (RP2D) of selinexor in combination with imatinib among unresectable and/or metastatic GIST patients with prior failure to at least imatinib for advanced/metastatic disease.

Cohort B:

  1. To evaluate the clinical benefit rate (CBR: CR+PR+SD ≥ 16 wks)

Secondary clinical study objectives (both cohorts A and B)

  1. To evaluate the clinical benefit rate (CBR: CR+PR+ SD ≥ 16 wks)
  2. To evaluate progression free survival (PFS)
  3. To evaluate overall survival (OS)
  4. To evaluate the objective response rate (ORR)
  5. To evaluate the safety profile according to CTCAE 4.03
  6. To compare PFS on selinexor and imatinib and on selinexor in monotherapy with PFS on last prior anti-cancer therapy.

Translational Study Objective - To explore the relationship between GIST genotype and CBR with selinexor and imatinib, and selinexor as single-agent

Pharmacokinetics Study Objective

  • To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.
Being tested
Selinexor, Imatinib
Keywords
GIST, MTD, Imatinib, Selinexor, Phase Ib, Phase II, Unresectable, Metastatic
Medical subject headings
Sarcoma, Drug-Related Side Effects and Adverse Reactions, Neoplasm Metastasis

What participants receive

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

  • SelinexorDrug

    Also called Drug Combination, Single agent

    oral selinexor given once weekly (Cohort A), oral selinexor given BIW (Cohort B)

  • ImatinibDrug

    Also called Drug Combination

    imatinib 400 mg, once daily (Cohort A)

Study groups in NCT04138381
Study groupRoleWhat they receive
selinexor as a single agent and in combination with imatinibOtherThis is a single-arm, two-cohort, open label phase Ib/II trial studying the combination of oral imatinib 400 mg, once daily, and oral selinexor given once weekly (Cohort A); and single-agent oral selinexor 60 mg BIW (Cohort B). The study will consist of: * Cohort A: an initial escalation phase (Ib) evaluating increasing doses of selinexor in combination with fixed doses of imatinib administered in repeated 28-day cycles in advanced/metastatic, imatinib-resistant GIST patients, followed by en expansion phase (II) testing for safety and preliminary evidence of antitumor activity * Cohort B: single-agent, fixed selinexor dose in the same target population
Receives: Drug: Selinexor; Drug: Imatinib

What is being measured

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

  1. Maximum tolerated dose (MTD) for the use of Imatinib in combination with Selinexor

    Maximum tolerated dose (MTD) is defined as the highest dose level with ≤1 out of 6 patients experiencing a dose limiting toxicity (DLT) during the first 28 days of treatment. Dose escalation cohort (Phase 1b) seeks to determine the frequency and characteristics of DLTs of the selinexor plus imatinib combination at each dose level during the first cycle of therapy. Phase Ib will be carried out in standard 3+3 format, based on the toxicities found during the first cycle of therapy.

    Measured: 32 months

  2. Clinical benefit rate (CBR) for the use of selinexor in monotherapy

    Clinical benefit rate (CBR) is defined as CR+PR+SD ≥ 16 wks

    Measured: 24 months

Secondary outcomes (7)

  1. Progression free survival (PFS)

    Efficacy measured by PFS assessed by median time. PFS is defined as the time between the date of first experimental treatment dose and the date of disease progression (according to RECIST 1.1 criteria).

    Measured: 32 months

  2. Overall survival (OS)

    Efficacy measured by OS. OS is defined as the time between the date of first experimental treatment dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive, or when the last enrolled patiens are followed up to for 12 months, whichever is early.

    Measured: 32 months

  3. Objective response rate (ORR)

    Efficacy measured by ORR. ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 and Choi criteria).

    Measured: 32 months

  4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.

    Toxicity will be graded and tabulated by using CTCAE 4.03.

    Measured: 32 months

  5. GIST genotype and CBR with selinexor and imatinib (Translational) Study Objective

    GIST genotype determinations and its correlation with response to the treatment with selinexor and imatinib in terms of clinical benefit (CBR).

    Measured: 32 months

  6. Measure the plasma concentration of imatinib and selinexor (Pharmacokinetics)Study Objective

    To measure the plasma concentration of imatinib and selinexor at limited timepoints specificed in schedule of assessment.

    Measured: 32 months

  7. Clinical benefit rate (CBR)

    Number of patient with CBR ≥ 30% lasting ≥ 16 weeks

    Measured: 24 months

Timeline

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

  1. First posted24 Oct 2019
  2. Study start16 Aug 2019
  3. Primary completion16 Apr 2023 (estimated)
  4. Study completion16 Apr 2023 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase Ib/II, single-arm, two-cohort, non-randomized, open-label, multicenter, national clinical trial, single agent, combinations products
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04138381
Sponsor's protocol ID
GEIS 41
Other IDs
2017-004761-28, 2017
Acronym
SeliGIST
Status last verified
Mar 2023
First submitted
16 Sep 2019
Last updated
27 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The final publication of the trial results will be written by the international coordinating investigators on the basis of the final analysis performed. The draft manuscript will be reviewed by the coordinating investigators and other co-authors. After revision the manuscript will be sent to a major scientific journal. Results obtained in the different strata may be separately published.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Selinexor and Imatinib in people with Maximum Tolerated Dose and GIST, run by Grupo Espanol de Investigacion en Sarcomas at 6 sites in Spain.

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 19 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Spain. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Results are not available in the source record.

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?

Maximum tolerated dose (MTD) for the use of Imatinib in combination with Selinexor (time frame: 32 months). The study lists 2 primary outcomes in all. 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 NCT04138381.

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 27 Mar 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in