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

NCT02384850 | Terminated Phase 1 Results

• 1 other identifier: SENTINEL
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

Brief 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.

Conditions

Colorectal Neoplasm

Keywords

metastatic

Outcome Measures

Primary Outcomes (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.

  28 days of treatment

Secondary Outcomes (4)

• Overall Response Rate

  2 years

• Progression Free Survival (PFS)

  2 years

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

  2 years

• Number of Patients Experiencing Adverse Events

  treatment start to up to 30 days after last dose

Study Arms (1)

Selinexor + mFOLFOX6

EXPERIMENTAL

Different Dose Levels of Selinexor will be evaluated in combination with mFOLFOX6 (see interventions)

Drug: Selinexor; Drug: Oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

Interventions

Selinexor DRUG

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.

Also known as: KPT-330

Selinexor + mFOLFOX6

Oxaliplatin DRUG

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

Also known as: oxalatoplatin

Selinexor + mFOLFOX6

5-FU DRUG

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

Also known as: 5-fluorouracil

Selinexor + mFOLFOX6

Folinic Acid DRUG

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

Also known as: leucovorin

Selinexor + mFOLFOX6

Eligibility Criteria

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

You may qualify if:

• 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):
• 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

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• GSO Global Clinical Research BV: lead
• Karyopharm Therapeutics Inc: collaborator

Study Sites (2)

University Hospital Antwerpen

Antwerp, 1200, Belgium

Location

University Hospital Hamburg

Hamburg, 20246, Germany

Location

Related Publications (1)

• 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.

  PMID: 32598257 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

selinexor; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr. Anne L. Kranich
• Organization: GSO Global Clinical Research B.V., EBC Amsterdam, Keizersgracht 62-64, 1015 CS Amsterdam

kranich@gsoglobal.com

+49 40 44 19 54 60

Study Officials

• Carsten Bokemeyer, Prof. Dr.

  University Hospital Hamburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 10, 2015
• Study Start: March 1, 2015
• Primary Completion: March 9, 2017
• Study Completion: March 9, 2017
• Last Updated: April 8, 2022
• Results First Posted: April 8, 2022

Record last verified: 2022-02

Locations

DE (1); BE (1)