CAPOXIRI+Bevacizumab vs. FOLFOXIRI+Bevacizumab for mCRC

Metastatic Colorectal Cancer Clinical Trial

— QUATTRO-II  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04097444
• Other study ID #: QUATTRO-II
• Status: Recruiting
• Phase: Phase 2
• Start date: October 11, 2019
• Est. completion date: August 31, 2022

Study information

• Verified date: October 2019
• Source: Chugai Pharmaceutical
• Contact: Tsunehiko Tateuchi
• Phone: +81-3-6304-5495
• Email: quattro-2_jimukyoku[@]acmedical.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: August 31, 2022
• Est. primary completion date: August 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Biological:
• Bevacizumab
Given IV

Drug:
• 5-fluorouracil
Given IV
• Leucovorin calcium
Given IV
• Irinotecan hydrochloride
Given IV
• Oxaliplatin
Given IV
• Capecitabine
Given PO

Locations

Country	Name	City	State
Japan	Ac Medical Inc.	Chuo Ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Chugai Pharmaceutical

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall response rate (ORR)		Up to 36 months
Secondary	Overall survival (OS)		Up to 36 months
Secondary	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	Up to 36 months
Secondary	Functional Assessment of Cancer Therapy (FACT) / Gynaecologic Oncology Group (GOG) Neurotoxicity 4		Up to 18 months