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Colorectal NeoplasmPhase 1SENTINELNCT02384850

Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor In Patients With Metastatic Colorectal Cancer

A Phase 1 study testing Selinexor, Oxaliplatin and 5-FU in people with Colorectal Neoplasm, run by GSO Global Clinical Research BV at 2 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This trial will evaluate the combination treatment of established chemotherapy regimen mFOLFOX6 with Selinexor, an oral Selective Inhibitor Of Nuclear Export, in patients with metastatic Colorectal Cancer. The purpose is to determine the maximum tolerated dose (MTD) of selinexor in combination with mFOLFOX6. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasm
What is being tested?
Selinexor, Oxaliplatin and 5-FU
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesin 2 countries
Study dates
Mar 2015to 9 Mar 2017
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients with histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present)
  • Patients who are feasible for treatment with FOLFOX (prior adjuvant or palliative treatment is allowed)
  • ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 1
  • Life expectancy > 3 months
  • Age ≥18 years
  • Haematologic function as follows (5% deviation allowed):
Show all 16Show fewer
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • platelets ≥ 100 x109/L
  • hemoglobin ≥ 9 g/dl or 5.59 mmol/l
  • Adequate liver function as follows (10% deviation allowed)
  • serum alanine transaminase (ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)
  • total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN)
  • Adequate renal function as follows (10% deviation allowed)
  • creatinine ≤ 1.5 x ULN
  • Signed written informed consent
  • Women of child-bearing potential must have a negative pregnancy test

Who cannot join

  • adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1 3. Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria) and/or known HIV infection; 4. Renal failure requiring haemodialysis or peritoneal dialysis; 5. Patients who are pregnant or breast-feeding; 6. Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications; 7. Presence of symptomatic Central nervous system (CNS) metastasis 8. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery, in particular oxaliplatin-induced peripheral neuropathy > grade 1.
  • 9. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Belgium1 site
  • University Hospital Antwerpen

    Antwerp, 1200

Other trials in Belgium

Germany1 site
  • University Hospital Hamburg

    Hamburg, 20246

Other trials in Germany

About this study

Official title: An Investigator Initiated Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor (KPT-330), An Oral Selective Inhibitor Of Nuclear Export (SINE), In Patients With Metastatic Colorectal Cancer

This trial will evaluate the combination treatment of established chemotherapy regimen mFOLFOX6 with Selinexor, an oral Selective Inhibitor Of Nuclear Export, in patients with metastatic Colorectal Cancer. The purpose is to determine the maximum tolerated dose (MTD) of selinexor in combination with mFOLFOX6.

Read the detailed description

This was a multi center, open-label, non-randomized phase I trial study to determine the MTD of a combination of mFOLFOX6 (Folinic Acid (Leucovorin)-Fluorouracil-Oxaliplatin) and selinexor in patients with metastatic colorectal cancer.

After screening and registration in the study, all enrolled patients were to be treated with oxaliplatin (85 mg/m² IV over 2 hours, Day 1), 5-FU (5-Fluorouracil 400 mg/m2 IV bolus, Day 1), leukovorin (400 mg/m2 IV over 2 hours, Day 1), and 5-FU (2,400 mg/m² continuous infusion, Days 1-3) every 2 weeks and escalating doses of selinexor as follows:

Patients in Dose Level 1 were to receive oral selinexor 40 mg on day 1, 3, and 8.

Patients in Dose Level 2 were to receive oral selinexor 60 mg on day 1, 3, and 8.

Patients in Dose Level 3 were to receive oral selinexor 80 mg on day 1, 3, and 8.

Patients in Dose Level -1 were to receive oral selinexor 20 mg on day 1, 3, and 8.

The MTD was defined as the highest dose level at which six patients had been treated with no toxicity and tolerance of the dose escalation of Selinexor with mFOLFOX6 was evaluated.

Six patients were to be initially treated in a cohort. Safety data were monitored in real time. As soon as last patient of the cohort (either 6th or 9th) reached day 28, safety data of all patients within that cohort were reviewed for decision about opening up a new cohort by moving to the next dose level or expand the cohort or discontinue dose escalation.

Being tested
Selinexor, Oxaliplatin, 5-FU, Folinic Acid
Keywords
metastatic
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

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

  • SelinexorDrug

    Also called KPT-330

    Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level 2: 60 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level 3: 80 mg on day 1, 3 and 8 in a two-weeks cycle. Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle.

  • OxaliplatinDrug

    Also called oxalatoplatin

    85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle

  • 5-FUDrug

    Also called 5-fluorouracil

    400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3

  • Folinic AcidDrug

    Also called leucovorin

    400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle

Study groups in NCT02384850
Study groupRoleWhat they receive
Selinexor + mFOLFOX6ExperimentalDifferent Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)
Receives: Drug: Selinexor; Drug: Oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

What is being measured

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

  1. Numbers of Patients With Dose Limiting Toxicities

    Primary objective is the determination of the maximum tolerated dose (MTD) of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer.

    Criteria to assess MTD was the experience of AEs > grade 3, discontinuation from study treatment due to adverse events or withdrawal of consent by the patients.

    Measured: 28 days of treatment

Secondary outcomes (4)
  1. Overall Response Rate

    Secondary objectives are to determine the efficacy and tolerability of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer by

    • Overall response rate (RR) (acc. to RECIST v1.1)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed byCT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: 2 years

  2. Progression Free Survival (PFS)

    Secondary objectives are to determine the efficacy and tolerability of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer by

    • Progression free survival (PFS) The disease status was measured by CT/MRI and evaluated according to RECIST 1.1 criteria every 8 weeks during treatment, at End of Treatment and every 3 weeks during Follow-up to determine time until patient has Progressive Disease (PD). PD is defined according to RECIST v1.1 at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: 2 years

  3. Number of Patients Still Alive at End of Study (Overall Survival)

    Secondary objectives are to determine the efficacy and tolerability of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer by

    • Overall survival (OS)

    Overall survial is defined as length of time from start of treatment that patients are still alive. For this time-to-event variables the Kaplan-Meier method was intended to be used

    Measured: 2 years

  4. Number of Patients Experiencing Adverse Events

    Secondary objectives are to determine the efficacy and tolerability of selinexor in combination with mFOLFOX6 in patients with metastatic colorectal cancer by

    • Toxicity (acc. to NCI Common Terminology Criteria for Adverse Events (CTC AE) v4.03)

    Measured: treatment start to up to 30 days after last dose

Timeline

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

  1. First posted10 Mar 2015 (estimated)
  2. Study startMar 2015
  3. Primary completion9 Mar 2017
  4. Study completion9 Mar 2017

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Dose level 1: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 IV over 46 hours (Day 1-3) Selinexor 40 mg, PO (Day 1, 3 and 8) Dose level 2: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 iv over 46 hours (Day 1-3) Selinexor 60 mg, PO (Day 1, 3 and 8) Dose level 3: Oxaliplatin at a dose of 85 mg/m2 iv over two hours (Day 1) 5-FU 400 mg/m2 iv bolus (Day 1) Leucovorin 400 mg/m2 iv over two hours (Day 1) 5-FU 2400 mg/m2 iv over 46 hours (Day 1-3) Selinexor 80 mg, PO (Day 1, 3 and 8) Dose level -1: Oxaliplatin at a dose of 85 mg/m2 IV over two hours (Day 1) 5-FU 400 mg/m2 IV bolus (Day 1) Leucovorin 400 mg/m2 IV over two hours (Day 1) 5-FU 2400 mg/m2 IV over 46 hours (Day 1-3) Selinexor 20 mg, PO (Day 1, 3 and 8)
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02384850
Sponsor's protocol ID
SENTINEL
Acronym
SENTINEL
Status last verified
Feb 2022
First submitted
2 Mar 2015
Last updated
8 Apr 2022
Data monitoring committee
No

Publications

  • Nilsson S, Stein A, Rolfo C, Kranich AL, Mann J, Papadimitriou K, Theile S, Amberg S, Bokemeyer C. Selinexor (KPT-330), an Oral Selective Inhibitor of Nuclear Export (SINE) Compound, in Combination with FOLFOX in Patients with Metastatic Colorectal Cancer (mCRC) - Final Results of the Phase I Trial SENTINEL. Curr Cancer Drug Targets. 2020;20(10):811-817. doi: 10.2174/1568009620666200628105727.

    PubMed 32598257

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Selinexor, Oxaliplatin and 5-FU in people with Colorectal Neoplasm, run by GSO Global Clinical Research BV at 2 sites in 2 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 16 inclusion and 2 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: stopped early, as of the sponsor's last update on 8 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium, Germany. 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 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.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Numbers of Patients With Dose Limiting Toxicities (time frame: 28 days of treatment). 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 NCT02384850, which also lists 1 linked publication.

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 8 Apr 2022.

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