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Metastatic Colorectal CancerPhase 2QUATTRO-IINCT04097444

CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC

A Phase 2 study testing Bevacizumab, 5-fluorouracil and Leucovorin calcium in people with Metastatic Colorectal Cancer, run by Chugai Pharmaceutical at 1 site in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Bevacizumab, 5-fluorouracil and Leucovorin calcium
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
1 siteJapan
Study dates
11 Oct 2019to 31 Aug 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 20Show fewer
  • 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.
  • Neutrophil count: ≥1,500 /cu.mm
  • Platelet count: ≥10.0 × 104/cu.mm
  • Hemoglobin concentration: ≥9.0 g/dL
  • Total bilirubin: ≤1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP): ≤2.5 times ULN (≤5 times ULN for metastases to liver)
  • Serum creatinine: ≤1.5 times ULN, or creatinine clearance: ≥30 mL/min
  • Urine protein: ≤2+ (if ≥3+, urine protein/creatinine ratio: <2.0)
  • UGT1A1 polymorphism is wild type or single heterozygous type -

Who cannot join

  • 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
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  • 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
  • Uncontrolled hypertension
  • Uncontrolled diabetes mellitus
  • Uncontrolled diarrhea
  • Peripheral sensory neuropathy (≥Grade 1)
  • Active peptic ulcer
  • Unhealed wound (except for suturing associated with implanted port placement)
  • Other clinically significant disease (such as interstitial pneumonia or renal impairment)
  • Major surgical procedure within 28 days prior to study treatment initiation (such as open chest, laparoscopy, thoracoscopic surgery, laparoscopic surgery), unless only colostomy is performed; open biopsy or suturing for major trauma within 14 days of study treatment initiation; or planned major surgical procedure during the study (open chest, laparoscopy) ("major surgical procedures" does not include central venous (CV) port insertion)
  • Physical defects of the upper gastrointestinal tract; malabsorption syndrome or difficulty taking oral medication
  • Pregnant, breastfeeding, positive pregnancy test (women who have menstruated in the last year will be tested), or women who are unwilling to use contraception; men who are unwilling to use contraception during the study
  • Active hepatitis B or C, or evidence of HIV infection
  • Previous chemotherapy for other malignancies (excluding hormone therapy for breast cancer)
  • Other active malignancies (synchronous malignancies, and asynchronous malignancies separated by a 5-year disease-free interval) (excluding malignancies that are expected to be completely cured, such as intramucosal carcinoma and carcinoma in situ)
  • Uncontrolled venous thromboembolism (unless clinically stable, asymptomatic, or appropriately treated with an anticoagulant)
  • Arterial thrombosis or arterial thromboembolism such as myocardial infarction, transient ischemic attack, or cerebrovascular attack in the last year prior to enrollment
  • Complications such as intestinal paralysis, intestinal obstruction, or gastrointestinal perforation, current or within 1 year prior to enrollment
  • Pleural effusion, ascites, or pericardial effusion requiring drainage
  • History of hypersensitivity to fluorouracil, levofolinate, oxaliplatin, irinotecan, bevacizumab and their excipients or Chinese hamster ovary cell proteins
  • History of adverse reactions to fluoropyrimidine drugs indicative of dihydropyrimidine dehydrogenase (DPD) deficiency
  • Systemic treatment required for, or evidence of, infections
  • Endoluminal stenting
  • Otherwise unsuitable for the study in the opinion of investigators -

Trial locations and contacts

1 site in 1 country.

Tsunehiko Tateuchi contact

+81-3-6304-5495

quattro-2_jimukyoku@acmedical.co.jp

Japan1 site, 1 recruiting

  • Ac Medical Inc.

    Chuo Ku, Tokyo, 104-0053

    Tsunehiko Tateuchi, +81-3-6304-5495, quattro-2_jimukyoku@acmedical.co.jp

    Takeshi Kato, M.D.,Ph.D.

    Recruiting

Other trials in Japan

About this study

Official title: Quadruplet 1st Line Treatment of CAPOXIRI Plus Bevacizumab Versus FOLFOXIRI Plus Bevacizumab for mCRC, Multicenter Randomised Phase II Study (QUATTRO-II)

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).

Read the detailed description

QUATTRO-II is an open-label, multicenter, randomised, phase II study to investigate the efficacy and safety of CAPOXIRI+BEV versus FOLFOXIRI+BEV in 1st line mCRC.

This study is composed two steps because of confirming of recommended dose (RD) for CAPOXIRI+BEV regimen.

  1. Dose finding step (Step1): CAPOXIRI+BEV doses findings were planned by 3+3 cohort design, register up to maximum of 12 cases.
  2. Randomised step (Step2): After confirmation of RD regarding CAPOXIRI+BEV, we will move to Step2 to compare the efficacy and safety between FOLFOXIRI+BEV and CAPOXIRI+BEV, register up to 65 cases.
Keywords
Metastatic colorectal cancer, bevacizumab, CAPOXIRI, FOLFOXIRI
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04097444
Study groupRoleWhat they receive
Step 1 (CAPOXIRI+ BEV)ExperimentalInduction 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.
Receives: Biological: Bevacizumab; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin; Drug: Capecitabine
Step 2 Arm A (FOLFOXIRI+ BEV)ExperimentalInduction 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.
Receives: Biological: Bevacizumab; Drug: 5-fluorouracil; Drug: Leucovorin calcium; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin
Step 2 Arm B (CAPOXIRI+ BEV)ExperimentalInduction 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.
Receives: Biological: Bevacizumab; Drug: Irinotecan hydrochloride; Drug: Oxaliplatin; Drug: Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 18 months

Secondary outcomes (4)

  1. Overall response rate (ORR)

    Measured: Up to 36 months

  2. Overall survival (OS)

    Measured: Up to 36 months

  3. Incidence of adverse events

    Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. All adverse events was collected in duration from starting treatment to whichever shorter "after 30 days from withdrawal treatment" or "later treatment

    Measured: Up to 36 months

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

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2019
  2. Study start11 Oct 2019
  3. Primary completion31 Aug 2022 (estimated)
  4. Study completion31 Aug 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
112 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04097444
Sponsor's protocol ID
QUATTRO-II
Acronym
QUATTRO-II
Status last verified
Oct 2019
First submitted
18 Sep 2019
Last updated
31 Oct 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 38901425

  • 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.

    PubMed 34019214

  • 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.

    PubMed 32703200

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, 5-fluorouracil and Leucovorin calcium in people with Metastatic Colorectal Cancer, run by Chugai Pharmaceutical at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 31 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Tsunehiko Tateuchi (+81-3-6304-5495, quattro-2_jimukyoku@acmedical.co.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04097444, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2019.

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