CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC

NCT04097444 | Unknown Phase 2 DMC

• 1 other identifier: QUATTRO-II
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

The objective is to compare the efficacy and safety of CAPOXIRI+BEV therapy versus FOLFOXIRI+BEV therapy as first-line therapy in patients with metastatic colorectal cancer (mCRC).

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic colorectal cancer; bevacizumab; CAPOXIRI; FOLFOXIRI

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS by investigator-reported measurements according to CT image. PFS was calculated from the day of treatment start to the first observation of progression disease (PD) or death from any cause.PD was defined as Overall Response by RECIST criteria v1.1 according to CT image.

  Up to 18 months

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 36 months

• Overall survival (OS)

  Up to 36 months

• Incidence of adverse events

  Up to 36 months

• Functional Assessment of Cancer Therapy (FACT) / Gynaecologic Oncology Group (GOG) Neurotoxicity 4

  Up to 18 months

Study Arms (3)

Step 1 (CAPOXIRI+ BEV)

EXPERIMENTAL

Induction therapy is followed by the maintenance therapy. \[Induction treatment: CAPOXIRI+BEV\] Administered for 6 cycles (a maximum of 8 cycles). BEV: 7.5mg/kg (d.i.v.) oxaliplatin (OX): 100/130 mg/sq.m (d.i.v.) irinotecan (IRI):150/180/200mg/sq.m (d.i.v.) CAP 1,600 mg/sq.m /day (p.o. day1-15) Administered every 3 weeks. OX/IRI dose is applied according to the progress of Step 1. \[Maintenance treatment: 5-fluorouracil (FU)/Levofolinate calcium (LV)+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV). 5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. day1-15) Administered every 3 weeks.

Biological: Bevacizumab; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin; Drug: Capecitabine

Step 2 Arm A (FOLFOXIRI+ BEV)

EXPERIMENTAL

Induction therapy is followed by the maintenance therapy. \[Induction treatment: FOLFOXIRI+BEV\] Administered for 8 cycles (a maximum of 12 cycles). BEV: 5mg/kg (d.i.v.) OX: 85 mg/sq.m (d.i.v.) IRI:165mg/sq.m (d.i.v.) LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. \[Maintenance treatment: 5-FU/LV+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV). 5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. Day1-15) Administered every 3 weeks.

Biological: Bevacizumab; Drug: 5-fluorouracil; Drug: Leucovorin calcium; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin

Step 2 Arm B (CAPOXIRI+ BEV)

EXPERIMENTAL

Induction therapy is followed by the maintenance therapy. \[Induction treatment: CAPOXIRI+BEV\] Administered for 6 cycles (a maximum of 8 cycles). BEV: 7.5mg/kg (d.i.v.) OX: 100/130 mg/sq.m (d.i.v.) IRI:150/180/200mg/sq.m (d.i.v.) CAP 1,600 mg/sq.m /day (p.o. day1-15) Administered every 3 weeks. Regarding to OX/IRI dose, RD will be confirmed at Step 1. \[Maintenance treatment: 5-FU/LV+BEV or CAP+BEV\] The following 5-FU/LV+BEV therapy will be repeated in 2-week cycles, or the following CAP+BEV therapy will be repeated in 3-week cycles (Physician's choice). No change in treatment regimen will be permitted after the selection of maintenance therapy (5-FU/LV+BEV or CAP+ BEV). 5-FU/LV+BEV: BEV:5mg/kg (d.i.v.) l-LV:200mg/sq.m (d.i.v.) 5-FU:3,200mg/sq.m (c.i.v.) Administered every 2 weeks. CAP+BEV: BEV: 7.5mg/kg (d.i.v.) CAP 1,600 mg/sq.m /day (po. day1-15) Administered every 3 weeks.

Biological: Bevacizumab; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: BEV

Step 1 (CAPOXIRI+ BEV); Step 2 Arm A (FOLFOXIRI+ BEV); Step 2 Arm B (CAPOXIRI+ BEV)

5-fluorouracil DRUG

Given IV

Also known as: 5-FU

Step 2 Arm A (FOLFOXIRI+ BEV)

Leucovorin calcium DRUG

Given IV

Also known as: LV

Step 2 Arm A (FOLFOXIRI+ BEV)

Irinotecan hydrochloride DRUG

Given IV

Also known as: IRI

Step 1 (CAPOXIRI+ BEV); Step 2 Arm A (FOLFOXIRI+ BEV); Step 2 Arm B (CAPOXIRI+ BEV)

Oxaliplatin DRUG

Given IV

Also known as: OX

Step 1 (CAPOXIRI+ BEV); Step 2 Arm A (FOLFOXIRI+ BEV); Step 2 Arm B (CAPOXIRI+ BEV)

Capecitabine DRUG

Given PO

Also known as: CAP

Step 1 (CAPOXIRI+ BEV); Step 2 Arm B (CAPOXIRI+ BEV)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Personal written informed consent is obtained after the study has been fully explained
• Histologically confirmed colon or rectal adenocarcinoma
• \*Excluding appendix cancer and anal canal cancer
• Clinically unresectable
• ≥20 years of age at enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 (≥71 years of age: PS score of 0)
• Measurable lesion according to RECIST ver. 1.1 criteria on contrast-enhanced chest, abdominal, or pelvic (trunk) CT (required within 28 days of enrollment)
• No previous chemotherapy for colon or rectal cancer
• \*Patients with confirmed relapse ≥24 weeks after completion of post-operative adjuvant chemotherapy can be enrolled
• Ras/Braf mutation analysis at enrollment identifies Ras/Braf status as either the wild type or mutant type.
• Vital organ functions meet the following criteria within 14 days before enrollment.
• If multiple test results are available in that period, the results closest to enrollment will be used. No blood transfusions or hematopoietic factor administration will be permitted within 2 weeks before the date on which measurements are taken.
• i. Neutrophil count: ≥1,500 /cu.mm
• ii. Platelet count: ≥10.0 × 104/cu.mm
• iii. Hemoglobin concentration: ≥9.0 g/dL

You may not qualify if:

• Previous radiation therapy in which ≥20% bone marrow was exposed to the radiation field
• Untreated brain metastases, spinal cord compression, or primary brain tumor
• History of central nervous system (CNS) disease (excluding asymptomatic lacunar infarction)
• Continuous systemic corticosteroid treatment is required
• Oral or parenteral (such as low molecular weight heparin) anticoagulant dose is not consistently (≥14 days) controlled. (Oral anticoagulants: conditions at high risk for bleeding, such as prothrombin time (PT)-international normalized ratio (INR) ≥3, clinically significant active bleeding (within 14 days of enrollment))
• Evidence of cardiovascular disease, cerebrovascular disorder (within 24 weeks), myocardial infarction (within 24 weeks), unstable angina pectoris, New York Heart Association (NYHA) classification ≥Grade II congestive heart failure, serious arrhythmias requiring drug therapy
• Previous treatment with an investigational drug within 28 days prior to enrollment, or participation in a study of an unapproved drug
• Any of the following comorbidities
• i. Uncontrolled hypertension
• ii. Uncontrolled diabetes mellitus
• iii. Uncontrolled diarrhea
• iv. Peripheral sensory neuropathy (≥Grade 1)
• v. Active peptic ulcer
• vi. Unhealed wound (except for suturing associated with implanted port placement)
• vii. Other clinically significant disease (such as interstitial pneumonia or renal impairment)

Sponsors & Collaborators

• Chugai Pharmaceutical: lead

Study Sites (1)

Ac Medical Inc.

Chuo Ku, Tokyo, 104-0053, Japan

RECRUITING

Related Publications (3)

• Bando H, Kotani D, Satake H, Hamaguchi T, Shiozawa M, Kotaka M, Masuishi T, Yasui H, Kagawa Y, Komatsu Y, Oki E, Yamamoto Y, Kawakami H, Misumi T, Taniguchi H, Yamazaki K, Muro K, Yoshino T, Kato T, Tsuji A. QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. FOLFOXIRI+bevacizumab as first-line treatment in patients with mCRC. Med. 2024 Sep 13;5(9):1164-1177.e3. doi: 10.1016/j.medj.2024.05.012. Epub 2024 Jun 19.

  PMID: 38901425 DERIVED

• Kotani D, Yoshino T, Kotaka M, Kawazoe A, Masuishi T, Taniguchi H, Yamazaki K, Yamanaka T, Oki E, Muro K, Komatsu Y, Bando H, Satake H, Kato T, Tsuji A. Combination therapy of capecitabine, irinotecan, oxaliplatin, and bevacizumab as a first-line treatment for metastatic colorectal cancer: Safety lead-in results from the QUATTRO-II study. Invest New Drugs. 2021 Dec;39(6):1649-1655. doi: 10.1007/s10637-021-01125-2. Epub 2021 May 21.

  PMID: 34019214 DERIVED

• Miyo M, Kato T, Yoshino T, Yamanaka T, Bando H, Satake H, Yamazaki K, Taniguchi H, Oki E, Kotaka M, Oba K, Miyata Y, Muro K, Komatsu Y, Baba H, Tsuji A. Protocol of the QUATTRO-II study: a multicenter randomized phase II study comparing CAPOXIRI plus bevacizumab with FOLFOXIRI plus bevacizumab as a first-line treatment in patients with metastatic colorectal cancer. BMC Cancer. 2020 Jul 23;20(1):687. doi: 10.1186/s12885-020-07186-5.

  PMID: 32703200 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin; Capecitabine

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; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Takeshi Kato, M.D., Ph.D.

  Department of Surgery, National Hospital Organization Osaka National Hospital.

  PRINCIPAL INVESTIGATOR

• Akihito Tsuji, M.D., Ph.D.

  Department of Medical Oncology, Kagawa University Hospital.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tsunehiko Tateuchi

CONTACT

+81-3-6304-5495; quattro-2_jimukyoku@acmedical.co.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 20, 2019
• Study Start: October 11, 2019
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: October 31, 2019

Record last verified: 2019-10

Locations

JP (1)