Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Study of CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC (QUATTRO-II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04097444
Recruitment Status : Not yet recruiting
First Posted : September 20, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Chugai Pharmaceutical

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).

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Biological: Bevacizumab Drug: 5-fluorouracil Drug: Leucovorin calcium Drug: Irinotecan hydrochloride Drug: Oxaliplatin Drug: Capecitabine Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Quadruplet 1st Line Treatment of CAPOXIRI Plus Bevacizumab Versus FOLFOXIRI Plus Bevacizumab for mCRC, Multicenter Randomised Phase II Study (QUATTRO-II)
Estimated Study Start Date : October 11, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: Step 1 (CAPOXIRI+ BEV)

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
Given IV
Other Name: BEV

Drug: Irinotecan hydrochloride
Given IV
Other Name: IRI

Drug: Oxaliplatin
Given IV
Other Name: OX

Drug: Capecitabine
Given PO
Other Name: CAP

Experimental: Step 2 Arm A (FOLFOXIRI+ BEV)

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
Given IV
Other Name: BEV

Drug: 5-fluorouracil
Given IV
Other Name: 5-FU

Drug: Leucovorin calcium
Given IV
Other Name: LV

Drug: Irinotecan hydrochloride
Given IV
Other Name: IRI

Drug: Oxaliplatin
Given IV
Other Name: OX

Experimental: Step 2 Arm B (CAPOXIRI+ BEV)

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
Given IV
Other Name: BEV

Drug: Irinotecan hydrochloride
Given IV
Other Name: IRI

Drug: Oxaliplatin
Given IV
Other Name: OX

Drug: Capecitabine
Given PO
Other Name: CAP




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 18 months ]
    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.


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Up to 36 months ]
  2. Overall survival (OS) [ Time Frame: Up to 36 months ]
  3. Incidence of adverse events [ Time Frame: Up to 36 months ]
    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

  4. Functional Assessment of Cancer Therapy (FACT) / Gynaecologic Oncology Group (GOG) Neurotoxicity 4 [ Time Frame: Up to 18 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Personal written informed consent is obtained after the study has been fully explained
  2. Histologically confirmed colon or rectal adenocarcinoma

    *Excluding appendix cancer and anal canal cancer

  3. Clinically unresectable
  4. ≥20 years of age at enrollment
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 (≥71 years of age: PS score of 0)
  6. Measurable lesion according to RECIST ver. 1.1 criteria on contrast-enhanced chest, abdominal, or pelvic (trunk) CT (required within 28 days of enrollment)
  7. No previous chemotherapy for colon or rectal cancer

    *Patients with confirmed relapse ≥24 weeks after completion of post-operative adjuvant chemotherapy can be enrolled

  8. Ras/Braf mutation analysis at enrollment identifies Ras/Braf status as either the wild type or mutant type.
  9. 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

    iv. Total bilirubin: ≤1.5 times upper limit of normal (ULN)

    v. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP): ≤2.5 times ULN (≤5 times ULN for metastases to liver)

    vi. Serum creatinine: ≤1.5 times ULN, or creatinine clearance: ≥30 mL/min

    vii. Urine protein: ≤2+ (if ≥3+, urine protein/creatinine ratio: <2.0)

  10. UGT1A1 polymorphism is wild type or single heterozygous type -

Exclusion Criteria:

  1. Previous radiation therapy in which ≥20% bone marrow was exposed to the radiation field
  2. Untreated brain metastases, spinal cord compression, or primary brain tumor
  3. History of central nervous system (CNS) disease (excluding asymptomatic lacunar infarction)
  4. Continuous systemic corticosteroid treatment is required
  5. 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))
  6. 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
  7. Previous treatment with an investigational drug within 28 days prior to enrollment, or participation in a study of an unapproved drug
  8. 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)

  9. 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)
  10. Physical defects of the upper gastrointestinal tract; malabsorption syndrome or difficulty taking oral medication
  11. 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
  12. Active hepatitis B or C, or evidence of HIV infection
  13. Previous chemotherapy for other malignancies (excluding hormone therapy for breast cancer)
  14. 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)
  15. Uncontrolled venous thromboembolism (unless clinically stable, asymptomatic, or appropriately treated with an anticoagulant)
  16. Arterial thrombosis or arterial thromboembolism such as myocardial infarction, transient ischemic attack, or cerebrovascular attack in the last year prior to enrollment
  17. Complications such as intestinal paralysis, intestinal obstruction, or gastrointestinal perforation, current or within 1 year prior to enrollment
  18. Pleural effusion, ascites, or pericardial effusion requiring drainage
  19. History of hypersensitivity to fluorouracil, levofolinate, oxaliplatin, irinotecan, bevacizumab and their excipients or Chinese hamster ovary cell proteins
  20. History of adverse reactions to fluoropyrimidine drugs indicative of dihydropyrimidine dehydrogenase (DPD) deficiency
  21. Systemic treatment required for, or evidence of, infections
  22. Endoluminal stenting
  23. Otherwise unsuitable for the study in the opinion of investigators -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04097444


Contacts
Layout table for location contacts
Contact: Tsunehiko Tateuchi 03-6304-5495 quattro-2_jimukyoku@acmedical.co.jp

Sponsors and Collaborators
Chugai Pharmaceutical
Investigators
Layout table for investigator information
Principal Investigator: 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.

Layout table for additonal information
Responsible Party: Chugai Pharmaceutical
ClinicalTrials.gov Identifier: NCT04097444     History of Changes
Other Study ID Numbers: QUATTRO-II
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Chugai Pharmaceutical:
Metastatic colorectal cancer
bevacizumab
CAPOXIRI
FOLFOXIRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Capecitabine
Oxaliplatin
Irinotecan
Fluorouracil
Calcium
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Calcium-Regulating Hormones and Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors