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

NCT01996306 | Completed Phase 3 DMC

• 2 other identifiers: AXEPTUMIN000012263
• Study Type: interventional
• Target: 650
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms

Keywords

AXEPT; Fluorouracil; CPT-11; XELIRI; Bevacizumab; FOLFIRI; Capecitabine; 2nd-line metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Time from the date of enrollment to death from any cause.

  Assessed until 1.5 years after the last patient enrolment

Secondary Outcomes (7)

• Progression-free survival (PFS)

  Assessed until 1.5 years after the last patient enrolment

• Time to treatment failure (TTF)

  Assessed until 1.5 years after the last patient enrolment

• Overall Response Rate (ORR)

  Assessed at 6, 12 week and thereafter every 8 weeks

• Disease Control Rate (DCR)

  Assessed at 6, 12 week and thereafter every 8 weeks

• Relative Dose Intensity

  Assessed until final dosing to the last patient

Study Arms (2)

FOLFIRI +/- Bevacizumab

ACTIVE COMPARATOR

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

Biological: Bevacizumab; Drug: CPT-11 (Irinotecan); Drug: 5-FU Bolus; Drug: 5-FU Infusion; Drug: l-LV (dl-LV)

XELIRI +/- Bevacizumab

EXPERIMENTAL

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

Biological: bevacizumab; Drug: CPT-11 (Irinotecan); Drug: Capecitabine

Interventions

bevacizumab 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.

Also known as: Avastin

FOLFIRI +/- Bevacizumab

CPT-11 (Irinotecan) DRUG

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

Also known as: Irinotecan

FOLFIRI +/- Bevacizumab

5-FU Bolus DRUG

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

Also known as: fluorouracil

FOLFIRI +/- Bevacizumab

5-FU Infusion DRUG

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

Also known as: fluorouracil

FOLFIRI +/- Bevacizumab

l-LV (dl-LV) DRUG

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

Also known as: Leucovorin

FOLFIRI +/- Bevacizumab

Capecitabine DRUG

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

Also known as: Xeloda

XELIRI +/- Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed inoperable colorectal adenocarcinoma excluding vermiform appendix cancer and anal canal cancer.
• Age ≥20 years at the time of informed consent
• ECOG performance status (PS) of 0-2
• Written informed consent prior to study-specific screening procedures
• Life expectancy of at least 90 days
• 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.
• 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

You may not qualify if:

• 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)
• With massive pleural effusion or ascites requiring intervention
• Radiological evidence of brain tumor or brain metastases
• Active infection including hepatitis
• 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)
• 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
• Previous treatment with irinotecan hydrochloride
• Current treatment with atazanavir sulfate
• Previous treatment with tegafur, gimeracil, and oteracil potassium within seven days before enrollment
• Pregnant or lactating females, and males and females unwilling to use contraception
• Requires continuous treatment with systemic steroids
• Psychiatric disability that would preclude study compliance
• Otherwise determined by the investigator to be unsuitable for participation in the study

Sponsors & Collaborators

• Epidemiological and Clinical Research Information Network: lead

Study Sites (1)

NPO Epidemiological and Clinical Research Information Network (ECRIN)

Kyoto, 606-8392, Japan

Location

Related Publications (2)

• 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.

  PMID: 29555258 DERIVED

• 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.

  PMID: 28007025 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms

Interventions

Bevacizumab; Irinotecan; Fluorouracil; Leucovorin; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kei Muro, MD

  Aichi Cancer Center Hospital, Japan

  PRINCIPAL INVESTIGATOR

• Tae Won Kim, MD, PhD

  ASAN Medical center, South Korea

  PRINCIPAL INVESTIGATOR

• Young Suk Park, MD, PhD

  Samsung Medical Center, South Korea

  PRINCIPAL INVESTIGATOR

• Ruihua Xu, MD, PhD

  Sun Yat-Sen University Cancer Center, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2013
• First Posted: November 27, 2013
• Study Start: December 2, 2013
• Primary Completion: November 20, 2017
• Study Completion: June 30, 2018
• Last Updated: January 8, 2019

Record last verified: 2019-01

Locations

JP (1)