A Phase III Study of 2nd-line XELIRI ± Bevacizumab vs. FOLFIRI ± Bevacizumab in mCRC

NCT ID: NCT01996306

Last Updated: 2019-01-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

650 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-02

Study Completion Date

2018-06-30

Brief Summary

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The primary purpose of this study is to determine the non-inferiority of overall survival XELIRI with or without Bevacizumab compared with FOLFIRI with or without Bevacizumab as Second-line therapy in Patient with Metastatic Colorectal Cancer.

Detailed Description

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Primary endpoint: Overall survival (OS), Secondary endpoints: Progression-free survival (PFS), Time to treatment failure (TTF), Overall response rate (ORR),Disease Control Rate (DCR), Relative dose intensity, Safety, and Correlation between UGT1A1 genotype and Safety.

Conditions

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Colorectal Neoplasms Neoplasm Metastasis Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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FOLFIRI +/- Bevacizumab

Bevacizumab 5 mg/kg IV 90-30 min Day 1 CPT-11 180 mg/m2 (150 mg/m2) IV 90 min Day 1 l-LV (dl-LV) 200 mg/m2 (400 mg/m2) IV 120 min Day 1 5-FU - bolus 400 mg/m2 IV bolus Day 1 5-FU - infusional 2400 mg/m2 IV continuous (46 hours) Day 1 - 3

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type BIOLOGICAL

5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.

CPT-11 (Irinotecan)

Intervention Type DRUG

150-180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle.

5-FU Bolus

Intervention Type DRUG

400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.

5-FU Infusion

Intervention Type DRUG

2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.

l-LV (dl-LV)

Intervention Type DRUG

200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.

XELIRI +/- Bevacizumab

Bevacizumab 7.5 mg/kg IV 90-30 min Day 1 CPT-11 200 mg/m2 (150 mg/m2) IV 90 min Day 1 Capecitabine 800 mg/m2 p.o. twice daily 14 Days consecutively

Group Type EXPERIMENTAL

bevacizumab

Intervention Type BIOLOGICAL

7.5mg/kg IV intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on Day 1 of a 3-week cycle.

CPT-11 (Irinotecan)

Intervention Type DRUG

150-200 mg/m2 intravenously administered over 90 minutes on day 1 of a 3-week cycle.

Capecitabine

Intervention Type DRUG

1600mg/m2/day oral on day 1 (evening) to day 15 (morning)of a 3-week cycle.

Interventions

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Bevacizumab

5 mg/kg intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on day 1 of a 2-week cycle.

Intervention Type BIOLOGICAL

CPT-11 (Irinotecan)

150-180 mg/m2 intravenously administered over 90 minutes on day 1 of a 2-week cycle.

Intervention Type DRUG

5-FU Bolus

400 mg/m2 intravenous bolus on day 1 of a 2-week cycle.

Intervention Type DRUG

5-FU Infusion

2400 mg/m2 continuous infusion over 46 hours on day 1 and 2 of a 2-week cycle.

Intervention Type DRUG

l-LV (dl-LV)

200 (dl-LV: 400) mg/m2 intravenously administered over 120 minutes on day 1 of a 2-week cycle.

Intervention Type DRUG

bevacizumab

7.5mg/kg IV intravenously administered over 90 minutes (can be reduced to 30 minutes at the minimum) on Day 1 of a 3-week cycle.

Intervention Type BIOLOGICAL

CPT-11 (Irinotecan)

150-200 mg/m2 intravenously administered over 90 minutes on day 1 of a 3-week cycle.

Intervention Type DRUG

Capecitabine

1600mg/m2/day oral on day 1 (evening) to day 15 (morning)of a 3-week cycle.

Intervention Type DRUG

Other Intervention Names

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Avastin Irinotecan fluorouracil fluorouracil Leucovorin Avastin Irinotecan Xeloda

Eligibility Criteria

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Inclusion Criteria

1. Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
2. Age ≥20 years at the time of informed consent
3. ECOG performance status (PS) of 0-2
4. Written informed consent prior to study-specific screening procedures
5. Life expectancy of at least 90 days
6. Withdrawal from first-line chemotherapy (regardless of containing molecular-targeted drugs) for metastatic colorectal cancer due to intolerable toxicity or progressive disease, or relapse within 180 days after the last dose of adjuvant chemotherapy.
7. Adequate organ function according to following laboratory values obtained within 14 days before enrolment (excluding patients who received blood transfusions or hematopoietic growth factors within 14 days before the laboratory test) Neutrophil count: ≥1500/mm3 Platelet count: ≥10.0 x 104/mm3 Hemoglobin: ≥9.0 g/dL Total bilirubin: ≤1.5 mg/dL AST, ALT: ≤100 IU/L (≤200 IU/I if liver metastases present) Serum creatinine: ≤1.5 mg/dL

Exclusion Criteria

1. History of other malignancy with a disease-free interval \<5 years (other than curatively treated cutaneous basal cell carcinoma, curatively treated carcinoma in situ of the cervix, and gastroenterological cancer confirmed to be cured by endoscopic mucosal resection)
2. With massive pleural effusion or ascites requiring intervention
3. Radiological evidence of brain tumor or brain metastases
4. Active infection including hepatitis
5. Any of the following complication:

i) Gastrointestinal bleeding or gastrointestinal obstruction (including paralytic ileus) ii) Symptomatic heart disease (including unstable angina, myocardial infarction, and heart failure) iii) Interstitial pneumonia or pulmonary fibrosis iv) Uncontrolled diabetes mellitus v) Uncontrolled diarrhea (that interferes with daily activities despite adequate therapy)
6. Any of the following medical history:

Myocardial infarction: History of one episode within one year before enrollment or two or more lifetime episodes i) Serious hypersensitivity to any of the study drugs ii) History of adverse reaction to fluoropyrimidines suggesting dihydropyrimidine dehydrogenase (DPD) deficiency
7. Previous treatment with irinotecan hydrochloride
8. Current treatment with atazanavir sulfate
9. Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
10. Pregnant or lactating females, and males and females unwilling to use contraception
11. Requires continuous treatment with systemic steroids
12. Psychiatric disability that would preclude study compliance
13. Otherwise determined by the investigator to be unsuitable for participation in the study
14. Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
15. History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
16. History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
17. Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
18. Current or recent (within 1 year) thromboembolism or cerebrovascular disease
19. Currently receiving or requires anticoagulation therapy (\> 325 mg/day of aspirin)
20. Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
21. Uncontrolled hypertension
22. Urine dipstick for proteinuria \>+2
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Epidemiological and Clinical Research Information Network

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kei Muro, MD

Role: PRINCIPAL_INVESTIGATOR

Aichi Cancer Center Hospital, Japan

Tae Won Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

ASAN Medical center, South Korea

Young Suk Park, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center, South Korea

Ruihua Xu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-Sen University Cancer Center, China

Locations

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NPO Epidemiological and Clinical Research Information Network (ECRIN)

Kyoto, , Japan

Site Status

Countries

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Japan

References

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Xu RH, Muro K, Morita S, Iwasa S, Han SW, Wang W, Kotaka M, Nakamura M, Ahn JB, Deng YH, Kato T, Cho SH, Ba Y, Matsuoka H, Lee KW, Zhang T, Yamada Y, Sakamoto J, Park YS, Kim TW. Modified XELIRI (capecitabine plus irinotecan) versus FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab, as second-line therapy for metastatic colorectal cancer (AXEPT): a multicentre, open-label, randomised, non-inferiority, phase 3 trial. Lancet Oncol. 2018 May;19(5):660-671. doi: 10.1016/S1470-2045(18)30140-2. Epub 2018 Mar 16.

Reference Type DERIVED
PMID: 29555258 (View on PubMed)

Kotaka M, Xu R, Muro K, Park YS, Morita S, Iwasa S, Uetake H, Nishina T, Nozawa H, Matsumoto H, Yamazaki K, Han SW, Wang W, Ahn JB, Deng Y, Cho SH, Ba Y, Lee KW, Zhang T, Satoh T, Buyse ME, Ryoo BY, Shen L, Sakamoto J, Kim TW. Study protocol of the Asian XELIRI ProjecT (AXEPT): a multinational, randomized, non-inferiority, phase III trial of second-line chemotherapy for metastatic colorectal cancer, comparing the efficacy and safety of XELIRI with or without bevacizumab versus FOLFIRI with or without bevacizumab. Chin J Cancer. 2016 Dec 22;35(1):102. doi: 10.1186/s40880-016-0166-3.

Reference Type DERIVED
PMID: 28007025 (View on PubMed)

Other Identifiers

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UMIN000012263

Identifier Type: OTHER

Identifier Source: secondary_id

AXEPT

Identifier Type: -

Identifier Source: org_study_id

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