Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruiting
Participants planned
124
Countries
1
Sites
7
Localised Colon Cancer (stage II-III)
Phase IIa: To analyse the potential effect of FOLFOXIRI as an intensive adjuvant treatment for ctDNA clearance as a surrogate biomarker of treatment efficacy. Phase IIb: To study differences on the conversion rate between an intensive adjuvant treatment (FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).
Key facts
- Sponsor
- Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 24 Jan 2025 → ongoing
- Decision date (initial)
- 2025-01-24
- Transition trial
- Yes
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518131-11-02
- EudraCT number
- 2021-000507-20
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy
Phase IIa: To analyse the potential effect of FOLFOXIRI as an intensive adjuvant treatment for ctDNA clearance as a surrogate biomarker of treatment efficacy.
Phase IIb: To study differences on the conversion rate between an intensive adjuvant treatment (FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).
Secondary objectives 4
- Phase IIb: 1. To evaluate the impact of intensive chemotherapy treatment on disease-free survival in patients with positive ctDNA at 24 months after end of treatment
- Phase IIb: 2. To evaluate the disease-free survival at 12 months after end of treatment, according to the seroconversion rate (ctDNA positive that becomes ctDNA negative) in each treatment arm.
- Phase IIb: 3.To assess the toxicity of triplet combination chemotherapy of FOLFOXIRI compared with conventional adjuvant treatment (CAPOX) for patients with localized colon cancer.
- Phase IIb: 4. To evaluate the impact of FOLFOXIRI compared with CAPOX on quality of life in patients with localized colon cancer.
Conditions and MedDRA coding
Localised Colon Cancer (stage II-III)
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-518131-11-00 | Phase II randomized trial to assess the effect of intensive vs standard adjuvant chemotherapy in localised colon cancer with circulating tumor DNA | Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA |
| 2024-518131-11-01 | Phase II randomized trial to assess the effect of intensive vs standard adjuvant chemotherapy in localised colon cancer with circulating tumor DNA | Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- CIRCULATE-SPAIN-01 trial written informed consent.
- Age ≥ 18 years and ≤ 75 years.
- Histologically confirmed diagnosis of operable stage II or stage III Colon Cancer.
- Postoperative, ctDNA positive.
- ECOG performance status 0-1.
- Normal organ functions, as follows: Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100.000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 x ULN AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
Exclusion criteria 16
- Patients having an MSI-H/MMRd tumor are excluded from the study (done according to standard clinical practice).
- History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Had an incomplete diagnostic colonoscopy and/or polyps’ removal for patients in whom the remaining colon was not removed or explored. Note: Patients with intraoperative complete colonoscopy or early perioperative complete colonoscopy and/or patients with incomplete colonoscopy, but who do have a CT colonoscopy or intraoperative colonoscopy, may be eligible to be recruited in the study.
- Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
- Current treatment with another investigational drug or participation in another investigational study
- Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Inadequate contraception (male or female patients) if of childbearing or procreational potential.
- Current clinically unresolved cardiovascular disease.
- Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
- Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
- Has a known DPD (DihydroPyrimidine Dehydrogenase) deficiency.
- Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection. Note: no testing for Hepatitis B and Hepatitis C is required.
- Has a known history of active TB (Bacillus Tuberculosis).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Phase IIa: Proportion of patients who negativize ctDNA after treatment.
- Phase IIb: Proportion of patients who negativize ctDNA after treatment in intensive group versus standard of care.
Secondary endpoints 4
- Phase IIb:Disease-free survival comparison between both treatment groups 24 months after treatment.
- Phase IIb: Disease-free survival comparison between both treatment groups 12 months after treatment.
- Phase IIb: Proportion of patients treated with triplet combination chemotherapy of FOLFOXIRI presenting adverse events in comparison to conventional adjuvant treatment (CAPOX).
- Phase IIb: QLQ-C30 Quality of Life of Cancer Patients and QLQ – CR29, comparison scores between groups at baseline, 3 months and end of treatment.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 16
Fluorouracilo Accord 50 mg/ml solución inyectable o para perfusión EFG
PRD415425 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 2400 mg/m2 milligram(s)/square meter
- Max total dose
- 3200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 71.868
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluorouracilo Accord 50 mg/ml solución inyectable o para perfusión EFG
PRD1972849 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2400 mg/m2 milligram(s)/square meter
- Max total dose
- 3200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 71.868
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluorouracilo Accord 50 mg/ml solución inyectable o para perfusión EFG
PRD8213537 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2400 mg/m2 milligram(s)/square meter
- Max total dose
- 3200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 71.868
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluorouracilo Accord 50 mg/ml solución inyectable o para perfusión EFG
PRD1972851 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2400 mg/m2 milligram(s)/square meter
- Max total dose
- 3200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 71.868
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluorouracilo Accord 50 mg/ml solución inyectable o para perfusión EFG
PRD1972850 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2400 mg/m2 milligram(s)/square meter
- Max total dose
- 3200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- 71.868
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FOLINATO CÁLCICO NORMON 50 mg Polvo y disolvente para solución inyectable EFG.
PRD403743 · Product
- Active substance
- Folinic Acid
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 200 mg/m2 milligram(s)/sq. meter
- Max total dose
- 200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- V03AF03 — CALCIUM FOLINATE
- Marketing authorisation
- 70341
- MA holder
- LABORATORIOS NORMON, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
FOLINATO CÁLCICO NORMON 350 mg Polvo para solución inyectable EFG.
PRD403742 · Product
- Active substance
- Folinic Acid
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 200 mg/m2 milligram(s)/sq. meter
- Max total dose
- 200 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- V03AF03 — CALCIUM FOLINATE
- Marketing authorisation
- 70340
- MA holder
- LABORATORIOS NORMON, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabina KERN PHARMA 150 mg comprimidos recubiertos con película EFG
PRD576043 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg/m2 milligram(s)/square meter
- Max total dose
- 1000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- 76108
- MA holder
- KERN PHARMA, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabina Kern Pharma 300 mg comprimidos recubiertos con película EFG
PRD3166938 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg/m2 milligram(s)/square meter
- Max total dose
- 1000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- 79.935
- MA holder
- KERN PHARMA, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabina KERN PHARMA 500 mg comprimidos recubiertos con película EFG
PRD576044 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg/m2 milligram(s)/square meter
- Max total dose
- 1000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- 76109
- MA holder
- KERN PHARMA, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Oxaliplatin Hospira 5 mg/ml concentrate for solution for infusion
PRD1169518 · Product
- Active substance
- Oxaliplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 130 mg/m2 milligram(s)/square meter
- Max total dose
- 130 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- PL 04515/0215
- MA holder
- HOSPIRA UK LIMITED,WALTON OAKS
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Oxaliplatin Hospira 5 mg/ml concentrate for solution for infusion
PRD4433783 · Product
- Active substance
- Oxaliplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 130 mg/m2 milligram(s)/square meter
- Max total dose
- 130 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- PL 04515/0215
- MA holder
- HOSPIRA UK LIMITED,WALTON OAKS
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Oxaliplatin Hospira 5 mg/ml concentrate for solution for infusion
PRD4433823 · Product
- Active substance
- Oxaliplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 130 mg/m2 milligram(s)/square meter
- Max total dose
- 130 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- PL 04515/0215
- MA holder
- HOSPIRA UK LIMITED,WALTON OAKS
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Irinotecán Hospira 20 mg/mL concentrado para solución para perfusión EFG.
PRD5146340 · Product
- Active substance
- Irinotecan Hydrochloride Trihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 165 mg/m2 milligram(s)/sq. meter
- Max total dose
- 165 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01CE02 — -
- Marketing authorisation
- 65.899
- MA holder
- PFIZER, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Irinotecán Hospira 20 mg/mL concentrado para solución para perfusión EFG.
PRD5146344 · Product
- Active substance
- Irinotecan Hydrochloride Trihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 165 mg/m2 milligram(s)/sq. meter
- Max total dose
- 165 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01CE02 — -
- Marketing authorisation
- 65.899
- MA holder
- PFIZER, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Irinotecán Hospira 20 mg/mL concentrado para solución para perfusión EFG.
PRD1165400 · Product
- Active substance
- Irinotecan Hydrochloride Trihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 165 mg/m2 milligram(s)/sq. meter
- Max total dose
- 165 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01CE02 — -
- Marketing authorisation
- 65.899
- MA holder
- PFIZER, S.L.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA
- Sponsor organisation
- Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA
- Address
- Avenida Menendez Y Pelayo 4
- City
- Valencia
- Postcode
- 46010
- Country
- Spain
Scientific contact point
- Organisation
- Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA
- Contact name
- UICEC
Public contact point
- Organisation
- Instituto De Investigacion Sanitaria Fundacion Para La Investigacion Del Hospital Clinico De Valencia-INCLIVA
- Contact name
- UICEC
Locations
1 EU/EEA country · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Authorised, recruiting | 124 | 7 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitari Vall D Hebron
Oncología, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Consorcio Hospital General Universitario De Valencia
Oncología, Provincial De Castellon, Avinguda Del Doctor Clara 19, Castello De La Plana
Hospital Clinico Universitario De Valencia
Oncología, Avenida Blasco Ibanez 17, 46010, Valencia
Fundacion Instituto Valenciano De Oncologia
Oncología, Calle Professor Beltran Baguena 8, 46009, Valencia
Hospital Universitario Reina Sofia
Oncología, Avenida Menendez Pidal S/n, 14004, Cordoba
Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL
Oncología, Avinguda De La Gran Via De L'hospitalet 199, 08908, L'Hospitalet De Llobregat
Hospital Del Mar
Oncología, Passeig Maritim De La Barceloneta 25-29, 08003, Barcelona
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 |
|---|---|---|---|---|---|
| Spain | 2025-01-24 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocolo Version 1_0 15-09-2021 | 1 |
| Protocol (for publication) | Protocolo Version 2_04-05-2023 Clean Version | 1 |
| Recruitment arrangements (for publication) | Procedimiento Reclutamiento CIRCULATE-SPAIN01 | 1 |
| Subject information and informed consent form (for publication) | HIP Fase IIa_Version 1_1_05_11_2021 | 1 |
| Subject information and informed consent form (for publication) | HIP Fase IIb_Version 1_1_05_11_2021 | 1 |
| Subject information and informed consent form (for publication) | HIP Molecular Version 1_0_15_092021 | 1 |
| Subject information and informed consent form (for publication) | HIP Molecular Version 2_0_04_05_2023 Clean version | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Capecitabina | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Fluorouracilo | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Irinotecan | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Leucovorin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | Oxiplatino | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-23 | Spain | Acceptable 2025-01-24
|
2025-01-24 |