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Colorectal NeoplasmsPhase 3AXEPTNCT01996306

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

A Phase 3 study testing Bevacizumab, CPT-11 (Irinotecan) and 5-FU Bolus in people with Colorectal Neoplasms and Neoplasm Metastasis, run by Epidemiological and Clinical Research Information Network at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Bevacizumab, CPT-11 (Irinotecan) and 5-FU Bolus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
650 participants
Where
1 siteJapan
Study dates
2 Dec 2013to 30 Jun 2018
Phase
Phase 3
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

  • 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

Who cannot join

  • 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:
  • 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)
Show all 24Show fewer
  • 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
  • Concurrent gastrointestinal perforation or history of gastrointestinal perforation with 1 year before enrollment
  • History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within 1 month prior to enrollment.
  • History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrollment
  • Unhealed wound (except suture wounds from implantation of a central venous port), gastrointestinal ulcer, or traumatic fracture
  • Current or recent (within 1 year) thromboembolism or cerebrovascular disease
  • Currently receiving or requires anticoagulation therapy (> 325 mg/day of aspirin)
  • Bleeding diathesis, coagulopathy, or coagulation factor abnormality (INR ≥1.5 within 14 days before enrollment)
  • Uncontrolled hypertension
  • Urine dipstick for proteinuria >+2

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • NPO Epidemiological and Clinical Research Information Network (ECRIN)

    Kyoto, 606-8392

Other trials in Japan

About this study

Official title: A Multinational, Randomized, Phase III Study of XELIRI With/Without Bevacizumab Versus FOLFIRI With/Without Bevacizumab As Second-line Therapy in Patients With Metastatic Colorectal Cancer

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.

Read the detailed description

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.

Being tested
Bevacizumab, CPT-11 (Irinotecan), 5-FU Bolus, 5-FU Infusion, l-LV (dl-LV)
Keywords
AXEPT, Fluorouracil, CPT-11, XELIRI, Bevacizumab, FOLFIRI, Capecitabine, 2nd-line metastatic colorectal cancer
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms

What participants receive

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

  • BevacizumabBiological

    Also called Avastin

    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)Drug

    Also called Irinotecan

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

  • 5-FU BolusDrug

    Also called fluorouracil

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

  • 5-FU InfusionDrug

    Also called fluorouracil

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

  • l-LV (dl-LV)Drug

    Also called Leucovorin

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

  • bevacizumabBiological

    Also called Avastin

    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)Drug

    Also called Irinotecan

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

  • CapecitabineDrug

    Also called Xeloda

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

Study groups in NCT01996306
Study groupRoleWhat they receive
FOLFIRI +/- BevacizumabActive comparatorBevacizumab 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
Receives: Biological: Bevacizumab; Drug: CPT-11 (Irinotecan); Drug: 5-FU Bolus; Drug: 5-FU Infusion; Drug: l-LV (dl-LV)
XELIRI +/- BevacizumabExperimentalBevacizumab 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
Receives: Biological: bevacizumab; Drug: CPT-11 (Irinotecan); Drug: Capecitabine

What is being measured

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

  1. Overall survival

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

    Measured: Assessed until 1.5 years after the last patient enrolment

Secondary outcomes (7)

  1. Progression-free survival (PFS)

    Time from the date of enrollment to the earlier of the date of confirmed progression or death from any cause.

    Measured: Assessed until 1.5 years after the last patient enrolment

  2. Time to treatment failure (TTF)

    Time from the date of enrollment to the earlier of the date of confirmed progression, death from any cause, or discontinuation of protocol treatment.

    Measured: Assessed until 1.5 years after the last patient enrolment

  3. Overall Response Rate (ORR)

    Proportion of eligible patients with measurable lesions with a best overall response of CR or PR assessed by the attending physician.

    Measured: Assessed at 6, 12 week and thereafter every 8 weeks

  4. Disease Control Rate (DCR)

    Proportion of best overall response of CR, PR, or SD assessed by the attending physician.

    Measured: Assessed at 6, 12 week and thereafter every 8 weeks

  5. Relative Dose Intensity

    will be calculated for each drug to evaluate treatment compliance in the all-treated population during the observation period.

    Measured: Assessed until final dosing to the last patient

  6. Incidence of Adverse Events (Adverse Reactions)

    The incidence of worst-grade adverse events (toxicities) on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm in all treated patients for the following events.

    Measured: Adverse events occurring within 30 days after treatment discontinuation will be followed until recovery

  7. Correlation between UGT1A1 genotype and safety

    The incidence of worst-grade adverse events on study as graded by NCI-CTCAE v 4.0 will be determined by treatment arm and UGT1A1 genotype in all treated patients with a known UGT1A1 genotype profile

    Measured: Adverse events occurring within 30 days after treatment discontinuation will be followed until recovery

Timeline

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

  1. First posted27 Nov 2013 (estimated)
  2. Study start2 Dec 2013
  3. Primary completion20 Nov 2017
  4. Study completion30 Jun 2018

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
650 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01996306
Sponsor's protocol ID
AXEPT
Other IDs
UMIN000012263
Acronym
AXEPT
Status last verified
Jan 2019
First submitted
22 Nov 2013
Last updated
8 Jan 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29555258

  • 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.

    PubMed 28007025

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bevacizumab, CPT-11 (Irinotecan) and 5-FU Bolus in people with Colorectal Neoplasms and Neoplasm Metastasis, run by Epidemiological and Clinical Research Information Network 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 7 inclusion and 24 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: finished, as of the sponsor's last update on 8 Jan 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Assessed until 1.5 years after the last patient enrolment). 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 NCT01996306, which also lists 2 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 8 Jan 2019.

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