Investigation of SCO-101 in Combination With FOLFIRI for Patients With Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI
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|ClinicalTrials.gov Identifier: NCT04247256|
Recruitment Status : Recruiting
First Posted : January 30, 2020
Last Update Posted : April 3, 2020
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer||Drug: FOLFIRI Protocol Drug: SCO-101||Phase 1 Phase 2|
This is a multi-center, open label, dose escalation, Phase 2 study of SCO-101 in combination with FOLFIRI in up to 50 mCRC patients. All patients included have previously had effect from treatment with FOLFIRI, but have now progressed (i.e. treatment failure due to acquired resistance).
FOLFIRI is a key anti-cancer chemotherapeutic combination in the treatment of several solid tumor cancers, e.g. colorectal cancer. Cancer resistance to FOLFIRI exposure is a well known phenomenon and can often be attributed to upregulation of cellular efflux pumps, e.g. ATP-Binding Cassette (ABC)G2 and ABCB1, involved in the efflux of the chemotherapeutic agents from the cancer cells and resulting in treatment failure.
SCO-101 is an inhibitor of ATP-Binding Cassette (ABC) efflux pumps and SRPK1 kinase which is responsible for phosphorylation of splicing factors, a key element involved in tumour growth.
The combination of SCO-101 with FOLFIRI is expected to inhibit the active efflux of chemotherapy molecules from the cancer cell thereby re-sensitizing it to the chemotherapeutic agents.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
This is a multi-center, open label, dose escalation, Phase 2 study of SCO-101 in combination with FOLFIRI in up to 50 mCRC patients.
Cohorts of FOLFIRI-resistant mCRC patients will be treated with SCO-101 in combination with FOLFIRI . Patients to be enrolled should previously have had either complete response (CR), partial response (PR), or stable disease (SD) (>16 weeks) on FOLFIRI.
The study is separated in two parts. Part 1 is a dose escalation part with a standard 3+3 design, designed to evaluate the safety and toxicity of the combination of SCO-101 and FOLFIRI, and to identify the maximum tolerated dose (MTD). A maximum of 5 cohorts have been planned. Starting dose of SCO-101 is 150 mg (cohort 1) and maximum dose is 350 mg (cohort 5).
Part 2 is the efficacy part, where patients are treated with the MTD dose identified in the first part and evaluated for efficacy and safety of the combination SCO-101 plus FOLFIRI.
|Masking:||None (Open Label)|
|Official Title:||An Open-label Phase II Prospective Clinical Trial to Investigate Safety, Tolerability, Maximum Tolerated Dose and Anti-tumor Effect for SCO-101 in Combination With FOLFIRI as a Safe and Efficient Treatment Modality in Metastatic or Advanced Colorectal Cancer (mCRC) Patients With Acquired FOLFIRI Resistant Cancer Disease.|
|Actual Study Start Date :||March 20, 2020|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||March 2021|
Experimental: Treatment arm
SCO-101 in combination with FOLFIRI
Drug: FOLFIRI Protocol
FOLFIRI standard treatment on day 5 to 7 (both days included) of a 14 day period. repeated bi-weekly
Investigational Medicinal Product, oral tablet administered on day 1 to 6 (both days included) of a 14 day period. repeated bi-weekly
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of combination of SCO-101 and FOLFIRI [ Time Frame: 4 cycles (each cycle is 2 weeks) ]Safety and tolerability by assessing the number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until four weeks after end of treatment to evaluate safety of SCO-101 in combination with FOLFIRI determined according to CTCAE version 5.0
- Maximum Tolerated Dose [ Time Frame: 1 cycle (each cycle is 2 weeks) ]Maximum tolerated dose (MTD) by evaluation of dose-limiting toxicities (DLTs) of SCO-101 in combination with FOLFIRI evaluated by CTCAE v. 5.0 (part 1 only)
- Objective Response Rate [ Time Frame: 4 cycles (each cycle is 2 weeks) ]Objective response rate (ORR) defined as CR and PR using the RECIST v. 1.1
- Progression Free Survival (PFS) [ Time Frame: Start of treatment to first objective sign of progression, assessed up to 100 months ]Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.
- Duration of Response [ Time Frame: From first response to progression, assessed up to 100 months ]Duration of response (from first response to progression)
- Duration of Response compared to prior Duration of response [ Time Frame: From first response to progression, assessed up to 100 months ]Duration of response (DOR) after administration of SCO-101 compared to DOR from patients initial FOLFIRI treatment regimen (without SCO-101).
- Overall Survival [ Time Frame: Up to 2 years ]Overall survival (OS) defined as time in months from the date of first study treatment to the date of death;
- Clinical Benefit Rate [ Time Frame: from benefit (CR, PR or SD > 16 weeks) to progression, assessed up to 100 months ]Clinical benefit rate (CBR) defined as the number of patients obtaining CR, PR, or SD > 16 weeks according to RECIST v.1.1.
- Pharmacokinetic profile of SCO-101 in combination with FOLFIRI [ Time Frame: First week of administration (study part 1 only) ]Pharmacokinetic profile of SCO-101 in blood samples
- ctDNA [ Time Frame: First 4 cycles of treatment (each cycle is 2 weeks) (study part 2 only) ]Change in ctDNA from baseline (prior first dose of SCO-101) until first CT scan
- Biomarker UGT1A1 [ Time Frame: Baseline (pre-treatment (all study parts)) ]Evaluation of Selected UGT1A1 polymorphism in a pre-treatment blood sample
- Biomarker IndiTreat(TM) [ Time Frame: Baseline (pre-treatment tumor biopsy (study part 2 only)) ]Efficacy of IndiTreat® to predict clinical response to SCO-101 treatment in combination with FOLFIRI from a tumor biopsy sample.
- Biomarkers ABCG2, ABCB1, SRPK1 [ Time Frame: Baseline (Pre-treatment biopsy (study part 2 only)) ]Efficacy of molecular biomarkers ABCB1/ABCG2/SRPK1 determined by immunohistochemistry to predict clinical response to SCO-101 treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04247256
|Contact: Peter M Vestlev, MD||+45 firstname.lastname@example.org|
|Aalborg University Hospital||Recruiting|
|Contact: Peter M Vestlev, MD|
|Principal Investigator:||Jacob Hagen Vasehus Schou, MD||Herlev and Gentofte Hospital|