Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
40
Countries
1
Sites
6
Colorectal cancer
To determine progression-free survival (PFS) of repeat sequential treatment with oxaliplatin-based chemotherapy (the Nordic FLOX regimen) and an immune checkpoint inhibitor (nivolumab) in previously untreated unresectable metastatic pMMR/MSS colorectal cancer (CRC).
Key facts
- Sponsor
- Akershus University Hospital
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 5 Oct 2022 → ongoing
- Decision date (initial)
- 2022-05-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Norwegian Cancer Society (Grants 215613-2020 and 245151-2022)
External identifiers
- EU CT number
- 2022-500027-76-00
- ClinicalTrials.gov
- NCT05504252
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To determine progression-free survival (PFS) of repeat sequential treatment with oxaliplatin-based chemotherapy (the Nordic FLOX regimen) and an immune checkpoint inhibitor (nivolumab) in previously untreated unresectable metastatic pMMR/MSS colorectal cancer (CRC).
Secondary objectives 2
- To determine safety and tolerability of the repeat sequential treatment.
- To monitor quality-of-life alterations during the therapy course.
Conditions and MedDRA coding
Colorectal cancer
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Patient has histologically verified CRC adenocarcinoma.
- Patient has radiologically measurable metastatic disease.
- Patient has not had previous systemic cytotoxic therapy for the metastatic disease, except for previous neoadjuvant treatment.
- Patient is eligible for the Nordic FLOX chemotherapy regimen.
Exclusion criteria 13
- Patient has initially resectable metastatic disease for which systemic therapy is deemed superfluous.
- Patient does not present any infradiaphragmatic metastatic manifestation.
- Patient has untreated or symptomatic brain metastasis (patient must be symptom-free without the use of corticosteroids).
- Patient experiences a period of less than 6 months since discontinuation of neoadjuvant or adjuvant oxaliplatin-containing chemotherapy.
- Patient is ineligible for full (100%) chemotherapy doses at first treatment cycle.
- Patient has had radiation therapy against the only measurable lesion within 4 weeks of start of study treatment.
- Patient has a nervous system disorder worse than grade 1 of the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
- Patient has any medical condition or has undergone any treatment within 4 weeks of start of study treatment that will preclude him/her from cancer immune therapy.
- Patient has any medical condition that will preclude him/her from receiving a component of the FLOX regimen.
- Patient has Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse.
- Patient has serum/plasma C-reactive protein (CRP) of 60 mg/L or higher.
- Patient does not meet the following requirements at baseline: adequate bone marrow function without current use of colony-stimulating factors (minimum values of neutrophils 1.5 x10e9/L, platelets 100 x10e9/L, hemoglobin 10 g/dL), adequate liver function (maximum values of AST/ALT 5 xULN and bilirubin 2 xULN; albumin value of 30 g/L or higher; INR within normal level), adequate renal function (maximum creatinine value of 1.5 xULN), protein in urine less than 2+ by dipstick (within 14 days prior to initiation of study treatment).
- Patient has any other reason, in the opinion of Clinical Investigator, not to participate in the study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- PFS: radiologic assessment following every 2 cycles each of FLOX and nivolumab, according to RECIST v1.1 and iRECIST
Secondary endpoints 6
- Safety: incidence of adverse events, as reported according to CTCAE v5.0, recorded on onboing basis and summarized at every visit.
- Tolerability: adverse event grading, as assessed by CTCAE v5.0, recorded on onboing basis and summarized at every visit.
- Objective response rate: the percentage of patients with a confirmed complete or partial response.
- Duration of response: the time from the first documentation of a complete or partial response to disease progression on active therapy.
- Secondary surgical curative-intent resection rate: the percentage of patients with a confirmed resection of metastatic disease with microscopically free margin (R0).
- Overall survival: the time from study enrollment to death of any cause.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
Fluorouracil Accord 50 mg/ml injeksjons-/infusjonsvæske, oppløsning
PRD979220 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1100 mg milligram(s)
- Max total dose
- 158400 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 12-9364
- MA holder
- ACCORD HEALTHCARE B.V.
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Oxaliplatin Fresenius Kabi 5 mg/ml konsentrat til infusjonsvæske, oppløsning
PRD409100 · Product
- Active substance
- Oxaliplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 190 mg milligram(s)
- Max total dose
- 13680 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- 07-5183
- MA holder
- FRESENIUS KABI NORGE AS
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941372 · Product
- Active substance
- Nivolumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 240 mg milligram(s)
- Max total dose
- 8640 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC17 — -
- Marketing authorisation
- EU/1/15/1014/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Kalsiumfolinat Pfizer 10 mg/ml injeksjonsvæske, oppløsning
PRD422407 · Product
- Active substance
- Folinic Acid
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 100 mg milligram(s)
- Max total dose
- 7200 mg milligram(s)
- Max treatment duration
- 36 Month(s)
- Authorisation status
- Authorised
- ATC code
- V03AF03 — CALCIUM FOLINATE
- Marketing authorisation
- 00-2462
- MA holder
- PFIZER AS
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 6
Ondansetron Bluefish 8 mg tabletter, filmdrasjerte
PRD2023549 · Product
- Active substance
- Ondansetron Hydrochloride Dihydrate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 8 mg milligram(s)
- Max total dose
- 960 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- A04AA01 — ONDANSETRON
- Marketing authorisation
- 06-4241
- MA holder
- BLUEFISH PHARMACEUTICALS AB
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Metoclopramide Accord 10 mg tabletter
PRD3834520 · Product
- Active substance
- Metoclopramide Hydrochloride Anhydrous
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 9000 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- A03FA01 — METOCLOPRAMIDE
- Marketing authorisation
- 15-10937
- MA holder
- ACCORD HEALTHCARE B.V.
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Adrenalin Aguettant 1 mg/ml injeksjonsvæske, oppløsning i ferdigfylt sprøyte
PRD8154283 · Product
- Active substance
- Epinephrine
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAMUSCULAR
- Max daily dose
- 1 mg milligram(s)
- Max total dose
- 4 mg milligram(s)
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- C01CA24 — EPINEPHRINE
- Marketing authorisation
- 20-13293
- MA holder
- LABORATOIRE AGUETTANT
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Dexamethasone Krka 4 mg tabletter
PRD5760024 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 8 mg milligram(s)
- Max total dose
- 960 mg milligram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- 16-11398
- MA holder
- KRKA, D.D., NOVO MESTO
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Solu-Cortef 250 mg pulver og væske til injeksjonsvæske, oppløsning i tokammerhetteglass
PRD422714 · Product
- Active substance
- Hydrocortisone
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 250 mg milligram(s)
- Max total dose
- 1000 mg milligram(s)
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB09 — HYDROCORTISONE
- Marketing authorisation
- 05-3196
- MA holder
- PFIZER AS
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD345336 · Product
- Active substance
- Paracetamol
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 4 g gram(s)
- Max total dose
- 500 g gram(s)
- Max treatment duration
- 30 Month(s)
- Authorisation status
- Authorised
- ATC code
- N02BE01 — PARACETAMOL
- Marketing authorisation
- 01-9312
- MA holder
- KARO PHARMA AS
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Akershus University Hospital
- Sponsor organisation
- Akershus University Hospital
- Address
- Sykehusveien 25
- City
- Loerenskog
- Postcode
- 1474
- Country
- Norway
Scientific contact point
- Organisation
- Akershus University Hospital
- Contact name
- Anne Hansen Ree
Public contact point
- Organisation
- Akershus University Hospital
- Contact name
- Anne Hansen Ree
Locations
1 EU/EEA country · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ongoing, recruitment ended | 40 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Akershus University Hospital
Department of Oncology, Sykehusveien 25, 1474, Loerenskog
St. Olavs Hospital Hf
Department of Oncology, Prinsesse Kristinas G. 3, 7030, Trondheim
Oslo University Hospital Hf
Department of Oncology, Taarnbygget, Kirkeveien 166, Oslo
Stavanger University Hospital
Department of Oncology, Postboks 8100, 4068, Stavanger
Helse Bergen HF
Department of Oncology, Haukelandsveien 22, 5021, Bergen
University Hospital Of North Norway HF
Department of Oncology, Sykehusvegen 38, 9019, Tromsoe
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Norway | 2022-10-05 | 2022-10-05 | 2025-03-14 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 20 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol modification nr 3 2022-500027-76-00 | 3.0 |
| Protocol (for publication) | METIMMOX-2 Protocol v1-2 | 1.2 |
| Summary of Product Characteristics (SmPC) (for publication) | Fluorouracil 12-9364 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Fluorouracil 12-9364 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Fluorouracil 12-9364 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Fluorouracil 12-9364 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Kalsiumfolinat 2000-02462 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Kalsiumfolinat 2000-02462 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Kalsiumfolinat 2000-02462 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Kalsiumfolinat 2000-02462 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Nivolumab tbdAri-opdivo-epar-product-information_no | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Nivolumab tbdAri-opdivo-epar-product-information_no | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Nivolumab tbdAri-opdivo-epar-product-information_no | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Nivolumab tbdAri-opdivo-epar-product-information_no | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Oxaliplatin 07-5183 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Oxaliplatin 07-5183 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Oxaliplatin 07-5183 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Oxaliplatin 07-5183 | 1 |
| Synopsis of the protocol (for publication) | Protocol synopsis | 1 |
| Synopsis of the protocol (for publication) | Protocol synopsis NO | 1 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-02-20 | Norway | Acceptable with conditions 2022-05-18
|
2022-05-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2022-06-15 | Norway | Acceptable 2022-07-01
|
2022-07-01 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2022-09-21 | Norway | Acceptable 2022-07-01
|
2022-09-21 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2022-11-30 | Norway | Acceptable 2022-07-01
|
2022-11-30 |
| 5 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-01-20 | Norway | Acceptable 2023-03-01
|
2023-03-21 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2023-05-03 | Norway | Acceptable 2023-03-01
|
2023-05-03 |
| 7 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-07 | Norway | Acceptable 2025-05-27
|
2025-05-28 |