Nivolumab Plus FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced Colorectal Cancer RASm/BRAFm Patients

NCT04072198 | Completed Phase 2 DMC

• 1 other identifier: GOIRC-03-2018
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multicentric single arm, open label trial. In this study patients candidated to a first line of chemotherapy for metastatic colorectal cancer will be treated with 8 cycles of folfoxiri plus bevacizumab plus nivolumab followed by a maintenance with bevacizumab plus nivolumab. Patients who do not progress during chemotherapy phase will receive bevacizumab plus nivolumab as maintenance therapy. Patients will be treated until disease progression, unacceptable toxicity or patient/physician decision.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  To demonstrate that adding nivolumab to standard colorectal first line chemotherapy improves the Overall Response Rate as determinated using RECIST 1.1 criteria

  36 months

Secondary Outcomes (5)

• Safety of combination

  36 months

• OS

  36 months

• TTP

  36 months

• Duration of response

  36 months

• Quality of life with QLQ-C30 questionnaire

  36 months

Study Arms (1)

FOLFOXIRI/Bevacizumab + Nivolumab

EXPERIMENTAL

Bevacizumab 5 mg/m2 Nivolumab 240 mg Irinotecan 165 mg/m2 iv (max 8 cycles) Oxaliplatin + leucovorin 200 mg/m2 (max 8 cycles) Fluorouracil 3200 mg/m2 (max 8 cycles)

Drug: Nivolumab; Drug: Bevacizumab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Leucovorin; Drug: fluoruracil

Interventions

Nivolumab DRUG

240 mg every 2 weeks for 8 cycles followed by maintenance

FOLFOXIRI/Bevacizumab + Nivolumab

Bevacizumab DRUG

5 mg/kg every 2 weeks for 8 cycles followed by maintenance

FOLFOXIRI/Bevacizumab + Nivolumab

Irinotecan DRUG

165 mg/m2 every 2 weeks for 8 cycles

FOLFOXIRI/Bevacizumab + Nivolumab

Oxaliplatin DRUG

85 mg/m2 every 2 weeks for 8 cycles

FOLFOXIRI/Bevacizumab + Nivolumab

Leucovorin DRUG

200 mg/m2 every 2 weeks for 8 cycles

FOLFOXIRI/Bevacizumab + Nivolumab

fluoruracil DRUG

3200mg/m2 every 2 weeks for 8 cycles

FOLFOXIRI/Bevacizumab + Nivolumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Male or female of 18-75 years of age on day of signing informed consent.
• Histologically confirmed diagnosis of colorectal cancer RAS/BRAF mutated.
• Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
• Patients suitable for first line chemotherapy.
• Life expectancy \> 3 months.
• At least one site of measurable disease per RECIST criteria.
• Performance status of 0-1 on the ECOG Performance Scale.
• Adequate organ function
• Availability at baseline of a representative formalin-fixed, paraffin-embedded (FFPE) diagnostic tumor specimen, as primary and/or metastatic tumor tissue block or as fifteen 5-micron unstained slides are allowed (the neoplastic cell content of each tumor sample will be assessed and in those cases with neoplastic cells \<50% a macro-dissection of the specimen will be performed, if possible).
• If DPD status is known it must be wild type. No restriction are applied if DPD status in unknown.
• Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study drug. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
• Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).

You may not qualify if:

• Prior chemotherapy, excluded patient treated in neo/adjuvant setting at least 12 months before diagnosis of metastatic disease.
• Radiotherapy to any site within 4 weeks before the study.
• Serious, non-healing wound, ulcer, or bone fracture.
• Evidence of bleeding diathesis or coagulopathy.
• Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
• Systemic corticosteroids within 2 weeks of the first dose of nivolumab.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment.
• Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
• Active and untreated brain (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are not using steroids for at least 7 days prior to trial treatment.
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger.
• Evidence of interstitial lung disease, active non-infectious pneumonitis, or a history of grade 3 or greater pneumonitis.
• Active infection requiring systemic therapy.
• History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection.
• Live vaccine within 30 days prior to the first dose of trial treatment.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (8)

Istituto Ospedaliero Fondazione Poliambulanza

Brescia, Italy

Location

Arnas Garibaldi

Catania, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

Istituto Nazionale Tumori Fondazione G.Pascale

Napoli, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

AUSL/IRCCS di Reggio Emilia

Reggio Emilia, Italy

Location

Policlinico Universitario Campus Bio-Medico

Roma, Italy

Location

IRCCS - Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

Related Publications (2)

• Damato A, Bergamo F, Antonuzzo L, Nasti G, Iachetta F, Romagnani A, Gervasi E, Larocca M, Pinto C. FOLFOXIRI/Bevacizumab Plus Nivolumab as First-Line Treatment in Metastatic Colorectal Cancer RAS/BRAF Mutated: Safety Run-In of Phase II NIVACOR Trial. Front Oncol. 2021 Dec 14;11:766500. doi: 10.3389/fonc.2021.766500. eCollection 2021.

  PMID: 34970487 DERIVED

• Damato A, Iachetta F, Antonuzzo L, Nasti G, Bergamo F, Bordonaro R, Maiello E, Zaniboni A, Tonini G, Romagnani A, Berselli A, Normanno N, Pinto C. Phase II study on first-line treatment of NIVolumab in combination with folfoxiri/bevacizumab in patients with Advanced COloRectal cancer RAS or BRAF mutated - NIVACOR trial (GOIRC-03-2018). BMC Cancer. 2020 Aug 31;20(1):822. doi: 10.1186/s12885-020-07268-4.

  PMID: 32867715 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab; Bevacizumab; Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Carmine Pinto, MD

  Gruppo Oncologico Italiano di Ricerca Clinica

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: September 26, 2019
• Primary Completion: August 30, 2024
• Study Completion: October 30, 2024
• Last Updated: March 13, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8)