Trial Outcomes & Findings for Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor In Patients With Metastatic Colorectal Cancer (NCT NCT02384850)

Last Updated: 2022-04-08

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

28 days of treatment

Results posted on

2022-04-08

Participant Flow

Participant milestones

Participant milestones
Measure	Selinexor 40 mg+ mFOLFOX6 Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Overall Study STARTED	4	6
Overall Study COMPLETED	2	4
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Selinexor 40 mg+ mFOLFOX6 Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selinexor 40mg + mFOLFOX6 n=4 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=6 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Total n=10 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Belgium	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Germany	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days of treatment

Population: The study was closed due to toxicity despite dose reduction to 20 mg Seiinexor.

Outcome measures

Outcome measures
Measure	Selinexor 40 mg+ mFOLFOX6 n=4 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=6 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Numbers of Patients With Dose Limiting Toxicities Discontinuation due to Withdrawal of Consent	2 Participants	2 Participants
Numbers of Patients With Dose Limiting Toxicities Discontinuation due to Adverse events	2 Participants	2 Participants
Numbers of Patients With Dose Limiting Toxicities Discontinuation due to Progressive Disease	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Due to the low number of patients, no conclusions can be drawn from analysis of the efficacy data.

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.

Outcome measures

Outcome measures
Measure	Selinexor 40 mg+ mFOLFOX6 n=4 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=6 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Overall Response Rate	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Four patients withdrew consent to further participate in the study before the first tumour assessment had been performed. No data on PD were available for those patients. Additionally, for two patients in cohort 2, no information on PD during the follow-up period is available.

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.

Outcome measures

Outcome measures
Measure	Selinexor 40 mg+ mFOLFOX6 n=2 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=2 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Progression Free Survival (PFS)	NA months Standard Deviation NA Based on limited number of participants, the Kaplan-Meier analyses could not be performed as planned.	NA months Standard Deviation NA Based on limited number of participants, the Kaplan-Meier analyses could not be performed as planned.

SECONDARY outcome

Timeframe: 2 years

Population: Due to sparse data set, no analysis with Kaplan-Meier methods was done.

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

Outcome measures

Outcome measures
Measure	Selinexor 40 mg+ mFOLFOX6 n=2 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=4 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Number of Patients Still Alive at End of Study (Overall Survival)	0 Participants	2 Participants

SECONDARY outcome

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

Population: All 10 patients were treated with at least one dose of Selinexor.

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)

Outcome measures

Outcome measures
Measure	Selinexor 40 mg+ mFOLFOX6 n=4 Participants Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=6 Participants Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Number of Patients Experiencing Adverse Events Patients with AEs of at least CTCAE Grade 3	4 Participants	6 Participants
Number of Patients Experiencing Adverse Events Patients with Selinexor related AEs of any Grade	4 Participants	4 Participants
Number of Patients Experiencing Adverse Events Patients with AEs of any CTCAE Grade	4 Participants	6 Participants
Number of Patients Experiencing Adverse Events Patients with Selinexor related AEs of at least Grade 3	4 Participants	5 Participants
Number of Patients Experiencing Adverse Events Patients with chemotherapy related AEs of any Grade	4 Participants	6 Participants
Number of Patients Experiencing Adverse Events Patients with chemotherapy related AEs of at least Grade 3	4 Participants	3 Participants
Number of Patients Experiencing Adverse Events Patients with AEs leading to discontinuation	2 Participants	2 Participants
Number of Patients Experiencing Adverse Events Patients with at least 1 SAE	2 Participants	3 Participants
Number of Patients Experiencing Adverse Events Patients with at least 1 SAE related to Selinexor	1 Participants	1 Participants
Number of Patients Experiencing Adverse Events Patients with at least 1 SAE related to chemotherapy	1 Participants	3 Participants

Adverse Events

Selinexor 40mg + mFOLFOX6

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Selinexor 20mg + mFOLFOX6

Serious events: 3 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Selinexor 40mg + mFOLFOX6 n=4 participants at risk Selinexor: Dose Level 1: 40 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle	Selinexor 20mg + mFOLFOX6 n=6 participants at risk Selinexor: Dose Level -1: 20 mg on day 1, 3 and 8 in a two-weeks cycle. Oxaliplatin: 85 mg/m² IV over 2 hours, Day 1 of a two-weeks cycle 5-FU: 400 mg/m² IV bolus, Day 1 of a two-weeks cycle 2,400 mg/m² continuous infusion IV, Days 1-3 Folinic Acid: 400 mg/m2 IV over 2 hours, Day 1 of a two-weeks cycle
Vascular disorders PULMONARY EMBOLISM	25.0% 1/4 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	0.00% 0/6 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
Metabolism and nutrition disorders HYPERGLYCEMIA	25.0% 1/4 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	0.00% 0/6 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
Gastrointestinal disorders CONSTIPATION	25.0% 1/4 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	0.00% 0/6 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
Infections and infestations HERPES ZOSTER	0.00% 0/4 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
Cardiac disorders ACUTE CORONARY SYNDROME	0.00% 0/4 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
General disorders GENERAL MALAISE	0.00% 0/4 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.
Nervous system disorders SEIZURE	0.00% 0/4 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.	16.7% 1/6 • Number of events 1 • Adverse Events were monitored from the date of informed consent until 30 days after the last dose of study medication (end of treatment visit). Patients who discontinued for reasons other than withdrawal of consent were followed for a maximum of 24 months for progression-free survival and overall survival, so deaths were monitored for up to 2 years for patients in follow-up.

Other adverse events

Additional Information

Dr. Anne L. Kranich

GSO Global Clinical Research B.V., EBC Amsterdam, Keizersgracht 62-64, 1015 CS Amsterdam

Phone: +49 40 44 19 54 60

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place