A Phase 2 Trial of SCO-101 in Combination With FOLFIRI for Patients With Metastatic Colorectal Cancer (mCRC) With Acquired Resistance to FOLFIRI

February 28, 2022 updated by: Scandion Oncology A/S

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.

This study evaluates the combination of SCO-101 to FOLFIRI for the treatment of metastatic colorectal cancer patients who have developed resistance to FOLFIRI treatment. The study is divided in two parts, where the first part evaluates the safety and toxicity of increasing doses of SCO-101 in combination with FOLFIRI at the same dose as the patient has previously developed resistance to. The second part of the study evaluates the safety and efficacy of the combination of FOLFIRI and SCO-101 at the dose level established in the first part.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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. 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

Enrollment (Anticipated)

35

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Recruiting
        • Aalborg Universitetshospital - Region Nordjylland
        • Contact:
        • Principal Investigator:
          • Morten Ladekarl, MD
      • Herlev, Denmark
      • Hillerød, Denmark
        • Recruiting
        • Hillerød Hospital
        • Contact:
        • Principal Investigator:
          • Fahimeh Andersen, MD
      • Roskilde, Denmark
        • Recruiting
        • Sjællands Universitetshospital, Roskilde
        • Contact:
        • Principal Investigator:
          • Lars Simon Reiter, MD
      • Sønderborg, Denmark
        • Recruiting
        • Sygehus Sønderjylland
        • Contact:
        • Principal Investigator:
          • Kim Wedervang, MD
      • Vejle, Denmark
        • Not yet recruiting
        • Vejle Sygehus
        • Contact:
        • Principal Investigator:
          • Torben Frøstrup Hansen, MD
  • Germany
      • Berlin, Germany
      • Bochum, Germany
        • Not yet recruiting
        • Catholic Hospital Bochum - St. Josef-Hospital
        • Contact:
        • Principal Investigator:
          • Anna-Lena Kraeft, MD
      • Ulm, Germany
        • Not yet recruiting
        • University Hospital of Ulm
        • Contact:
        • Principal Investigator:
          • Thomas J. Ettrich, MD
  • Spain
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital Universitario Valle de Hebron
        • Contact:
        • Principal Investigator:
          • Elena Élez Fernáncez, MD
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital de la Santa Creu in Sant Pau
        • Contact:
        • Principal Investigator:
          • David Paez Lopez-Bravo, MD
      • Valencia, Spain
        • Not yet recruiting
        • Hospital Clínico Universitario in Valencia
        • Contact:
        • Principal Investigator:
          • Susana Rosell, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: Subjects are required to meet all of the following criteria for enrollment into the applicable stage (stage 1, stage 2 or stage 3) of the study:

  1. Ability to understand and willingness to provide written informed consent before any trial-related activities.
  2. Age 18 years or older.
  3. Histologically verified colorectal adenocarcinoma.
  4. Non-resectable mCRC in patients A. Stage 1 only: with or without known BRAF, KRAS or repair enzyme mutations. B. Stage 2 and stage 3 only: without known BRAF, KRAS or repair enzyme mutations

  5. A. Stage 1 only: Documented progressive disease on FOLFIRI treatment regimen (with or without antiangiogenetic and EGFR inhibitory biological treatment).

    B. Stage 2 and stage 3 only: Documented progressive disease with a prior benefit (SD for more than 16 weeks, or CR or PR) on FOLFIRI treatment regimen (with or without antiangiogenetic and EGFR inhibitory biological treatment).

  6. Maximum reduction of 33% in prior dose of FOLFIRI.
  7. No indication for treatment with an oxaliplatin-containing treatment regimen. The patient may have received oxaliplatin treatment after treatment with FOLFIRI.
  8. A. Stage 1 only: Evaluable disease by CT scan or MRI. B. Stage 2 and stage 3 only: Measurable disease by CT scan or MRI, according to RECIST. 1.1.
  9. Performance status of ECOG ≤ 1.
  10. Recovered to Grade 1 or less from prior surgery or acute toxicities of prior radiotherapy or treatment with cytotoxic or biologic agents.
  11. ≥ 2 weeks must have elapsed since any prior surgery.

  12. Adequate conditions as evidenced by the following clinical laboratory values:

    • Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
    • Haemoglobin ≥ 6.0 mmol/L
    • Platelets ≥ 100 x 109 /L
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN*
    • Total serum bilirubin ≤ 1.0 ULN**
    • Alkaline phosphatase ≤ 2.5 x ULN*
    • Creatinine ≤ 1.5 ULN
    • eGFR within normal limits.
    • Adequate blood clothing function as defined by the International Normalized Ratio (INR) ≤ 1.2;
  13. Life expectancy equal to or longer than 3 months.
  14. Sexually active males and females of child-producing potential must use highly effective contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for the study duration and at least 6 months after the last dose of study drug.

  15. Signed informed consent.

    • AST is not mandatory. In case of known liver metastases with ALT and AST ≤ 5 x ULN and/or alkaline phosphatase ≤ 5 x ULN: Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor.

      • Unconjugated bilirubin may be measured as the difference between total bilirubin and conjugated bilirubin.

Exclusion Criteria: Subjects meeting any of the following criteria will be excluded from enrollment:

  1. Concurrent chemotherapy, radiotherapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.
  2. Malabsorption syndrome or previous surgeries with resection of the stomach or small intestine, whereby absorption of SCO-101 may be affected. This includes patients with ileostomy.
  3. Difficulty in swallowing tablets.
  4. Clinical symptoms of CNS metastases requiring steroids.
  5. Any active infection requiring parenteral or oral antibiotic treatment.
  6. Known HIV positivity.
  7. Known active hepatitis B or C.

  8. Clinical significant (i.e. active) cardiovascular disease:

    • Stroke within ≤ 6 months prior to day 1
    • Transient ischemic attach (TIA) within ≤ 6 months prior to day 1
    • Myocardial infarction within ≤ 6 months prior to day 1
    • Unstable angina
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF)
    • Serious cardiac arrhythmia requiring medication
  9. Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
  10. Other medications or conditions that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results. Other severe medical conditions, including serious heart disease, unstable diabetes, uncontrolled hypercalcemia, clinically active infections or previous organ transplants. Participation in another clinical trial with experimental medication within 30 days prior to registration.
  11. Known hypersensitivity to irinotecan, 5-FU or capecitabine
  12. Pregnant women or women who are breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: SCO-101
Investigational Medicinal Product, oral tablet administered on day 1 to 6 (both days included) of a 14 day period. repeated bi-weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 cycles (each cycle is 2 weeks)
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)
1 cycle (each cycle is 2 weeks)
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
4 cycles (each cycle is 2 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Start of treatment to first objective sign of progression, assessed up to 100 months
Duration of Response
Time Frame: From first response to progression, assessed up to 100 months
Duration of response (from first response to progression)
From first response to progression, assessed up to 100 months
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).
From first response to progression, assessed up to 100 months
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;
Up to 2 years
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.
from benefit (CR, PR or SD > 16 weeks) to progression, assessed up to 100 months
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
First week of administration (study part 1 only)
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
First 4 cycles of treatment (each cycle is 2 weeks) (study part 2 only)
Biomarker UGT1A1
Time Frame: Baseline (pre-treatment (all study parts))
Evaluation of Selected UGT1A1 polymorphism in a pre-treatment blood sample
Baseline (pre-treatment (all study parts))
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.
Baseline (pre-treatment tumor biopsy (study part 2 only))
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
Baseline (Pre-treatment biopsy (study part 2 only))

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Scandion Oncology A/S

Collaborators

TFS Trial Form Support

Investigators

  • Principal Investigator: Jacob Hagen Vasehus Schou, MD, Herlev and Gentofte Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2020

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

June 30, 2022

Study Registration Dates

First Submitted

January 23, 2020

First Submitted That Met QC Criteria

January 28, 2020

First Posted (Actual)

January 30, 2020

Study Record Updates

Last Update Posted (Actual)

March 2, 2022

Last Update Submitted That Met QC Criteria

February 28, 2022

Last Verified

December 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCO101-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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