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

NCT ID: NCT04247256

Last Updated: 2022-03-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-14
• Study Completion Date: 2022-06-30

Brief Summary

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.

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment arm

SCO-101 in combination with FOLFIRI

Group Type: EXPERIMENTAL

FOLFIRI Protocol

Intervention Type: DRUG

FOLFIRI standard treatment on day 5 to 7 (both days included) of a 14 day period. repeated bi-weekly

SCO-101

Intervention Type: DRUG

Investigational Medicinal Product, oral tablet administered on day 1 to 6 (both days included) of a 14 day period. repeated bi-weekly

Interventions

FOLFIRI Protocol

FOLFIRI standard treatment on day 5 to 7 (both days included) of a 14 day period. repeated bi-weekly

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

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

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

Scandion Oncology A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacob Hagen Vasehus Schou, MD

Role: PRINCIPAL_INVESTIGATOR

Herlev and Gentofte Hospital

Locations

Aalborg Universitetshospital - Region Nordjylland

Aalborg, , Denmark

Site Status: RECRUITING

Herlev Hospital

Herlev, , Denmark

Site Status: RECRUITING

Hillerød Hospital

Hillerød, , Denmark

Site Status: RECRUITING

Sjællands Universitetshospital, Roskilde

Roskilde, , Denmark

Site Status: RECRUITING

Sygehus Sønderjylland

Sønderborg, , Denmark

Site Status: RECRUITING

Vejle Sygehus

Vejle, , Denmark

Site Status: NOT_YET_RECRUITING

Charité

Berlin, , Germany

Site Status: NOT_YET_RECRUITING

Catholic Hospital Bochum - St. Josef-Hospital

Bochum, , Germany

Site Status: NOT_YET_RECRUITING

University Hospital Of Ulm

Ulm, , Germany

Site Status: NOT_YET_RECRUITING

Hospital de la Santa Creu in Sant Pau

Barcelona, , Spain

Site Status: NOT_YET_RECRUITING

Hospital Universitario Valle de Hebrón

Barcelona, , Spain

Site Status: NOT_YET_RECRUITING

Hospital Clínico Universitario in Valencia

Valencia, , Spain

Site Status: NOT_YET_RECRUITING

Countries

Denmark; Germany; Spain

Central Contacts

Peter M Vestlev, MD

Role: CONTACT

pmv@scandiononcology.com

+45 22779696

Facility Contacts

Morten M Ladekarl, MD

Role: primary

jakob.hagen.vasehus.schou@regionh.dk

Jakob Hagen Vasehus Schou, MD

Role: primary

jakob.hagen.vasehus.schou@regionh.dk

Fahimeh Andersen, MD

Role: primary

Fahimeh.Andersen@regionh.dk

Lars Simon Reiter, MD

Role: primary

lsir@regionsjaelland.dk

Kim Wedervang, MD

Role: primary

kim.wedervang@rsyd.dk

Torben Frøstrup Hansen, MD

Role: primary

Torben.Hansen@rsyd.dk

Sebastian Stintzing, MD

Role: primary

sebastian.stintzing@charite.de

Anna-Lena Kraeft

Role: primary

Anna-lena.kraeft@rub.de

Thomas J. Ettrich, MD

Role: primary

thomas.ettrich@uniklinik-ulm.de

David Paez Lopez-Bravo, MD

Role: primary

DPaez@santpau.cat

Elena Élez Fernáncez, MD

Role: primary

meelez@vhio.net

Susana Rosell, MD

Role: primary

susanark@hotmail.com

Other Identifiers

SCO101-001

Identifier Type: -

Identifier Source: org_study_id