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Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer (ACTICCA-1)

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ClinicalTrials.gov Identifier: NCT02170090
Recruitment Status : Recruiting
First Posted : June 23, 2014
Last Update Posted : September 23, 2020
Sponsor:
Collaborators:
Deutsche Krebshilfe e.V., Bonn (Germany)
Cancer Research UK
Australasian Gastro-Intestinal Trials Group
Dutch Cancer Society
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf

Tracking Information
First Submitted Date  ICMJE June 18, 2014
First Posted Date  ICMJE June 23, 2014
Last Update Posted Date September 23, 2020
Study Start Date  ICMJE April 2014
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2017)
Disease free survival (DFS) [ Time Frame: Disease free survival rate at 24 months (DFSR@24) ]
DFS
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2014)
Disease free survival (DFS) [ Time Frame: Disease free survival rate at 24 months (DFSR@24) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 2, 2017)
  • Disease free survival rate at 24 months (DFSR@24) [ Time Frame: 24 months ]
    DSFR
  • Recurrence free survival [ Time Frame: 24 months ]
    RFS
  • Overall survival [ Time Frame: 84 months ]
    OS
  • Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03) [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 48 months ]
    QOL
  • Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD) [ Time Frame: 48 months ]
  • Rate and severity of biliary tract infections [ Time Frame: 48 months ]
  • Patterns of disease recurrence [ Time Frame: 48 months ]
  • locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence) [ Time Frame: 48 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2014)
  • Disease free survival rate at 24 months (DFSR@24) [ Time Frame: 24 months ]
  • Overall survival [ Time Frame: 84 months ]
  • Safety and tolerability (assessed by the rate of patients with adverse events according to NCI CTC AE v4.03) [ Time Frame: 24 months ]
  • Quality of life [ Time Frame: 48 months ]
  • Function of biliodigestive anastomosis (in terms of surgical revision, requirement for PTCD) [ Time Frame: 48 months ]
  • Rate and severity of biliary tract infections [ Time Frame: 48 months ]
  • Patterns of disease recurrence [ Time Frame: 48 months ]
  • locoregional control (assessed by the rate of patients with hepatic or locoregional recurrence) [ Time Frame: 48 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
Official Title  ICMJE Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Cholangiocarcinoma and Muscle Invasive Gall Bladder Carcinoma (ACTICCA-1 Trial)
Brief Summary This is a multicenter, prospective, randomized, controlled phase III trial designed to assess the clinical performance of gemcitabine with cisplatin and observation vs. standard of care (observation alone in stage 1 and capecitabine and observation in stage 2) in patients after curative intent resection of BTC including an embedded sub-study for R1 resected patients receiving additional chemoradiation.
Detailed Description

The ACTICCA-1 investigator initiated trial is funded by the Deutsche Krebshilfe (grant number 70110215, 70112047). With respect to data obtained in the ABC-02 trial, the combination of cisplatin and gemcitabine for 24 weeks as investigational treatment was selected. Based on adjuvant trials in pancreatic cancer (e.g. ESPAC IV) with a comparable postoperative recovery time, inclusion of patients within a maximum interval of 16 weeks between surgery and start of CTx was chosen. Gemcitabine and cisplatin has a relevantly higher cumulative dose of gemcitabine 18 vs. 12 applications and may thus be of increased efficacy compared to the gemcitabine/oxaliplatin regimen applied in the PRODIGE 12 trial.

Based on the data of the BILCAP trial showing an improvement in median overall survival for capecitabine compared to observation alone presented at the annual meeting of the American Society of Clinical Oncology on June 4th 2017 in Chicago by the British BILCAP trial group, capecitabine has evolved as the new standard of care after curative intent resection of biliary tract cancer.

Based on these data the comparative efficacy of gemcitabine/cisplatin and capecitabine had to be established.

Therefore, the ACTICCA trial was amended to compare gemcitabine and cisplatin to the newly established standard regimen in the adjuvant setting capecitabine, aiming for superiority of the combination regimen vs. the oral monotherapy This was based on the BILCAP protocol, applying the similar dosing, assessments and dose modifications as in BILCAP, including dose calculation and patient diary.

As data of recent trials like the French PRODIGE 12/ACCORD 18 trial have clearly shown that in terms of efficacy of an adjuvant chemotherapy there is no difference between cholangiocarcinoma and gall bladder carcinoma, these two subtypes are pooled and location was added as an stratification factor.

Randomization will be 1:1 with adjuvant CTx for 24 weeks and imaging every 12 weeks in the experimental arm and standard of care (capecitabine) and observation in the control arm.

The primary endpoint is DFS and secondary endpoints include recurrence free survival, OS, safety and tolerability of adjuvant CTx, quality of life, and patterns of disease recurrence.

In addition, eligible patients with R1 resection included in sites participating in the radiotherapy sub-study will be randomized between 24 weeks chemotherapy (gemcitabine/cisplatin or capecitabine) or 18 weeks of chemotherapy (gemcitabine/cisplatin or capecitabine) followed by chemoradiation with capecitabine.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cholangiocarcinoma
  • Gall Bladder Carcinoma
Intervention  ICMJE
  • Drug: Gemcitabine
    Gemcitabine 1000mg/m2
  • Drug: Cisplatin
    Cisplatin 25mg/m2
  • Drug: Capecitabine
    Capecitabine 1250mg/m2
Study Arms  ICMJE
  • Experimental: Gemcitabine plus Cisplatin

    Chemotherapy will be administered on days 1 and 8 every 3 weeks, Cisplatin (25 mg per square meter of body-surface area) and Gemcitabine (1000 mg per square meter) for 24 weeks (8 cycles)

    and Observation

    Second randomisation for R1 resected patients: 8 cycles Cisplatin and Gemcitabin or 6 cycles Cisplatin and Gemcitabin followed by IMRT with capecitabine

    Interventions:
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Active Comparator: Capecitabine

    Capecitabine will be administered from day 1 to 14 every 3 weeks (1250 mg per square meter of body-surface area, twice daily) for 24 weeks (8 cycles)

    and Observation

    Second randomisation for R1 resected patients: 8 cycles capecitabine or 6 cycles capecitabine followed by IMRT with capecitabine

    Intervention: Drug: Capecitabine
Publications * Stein A, Arnold D, Bridgewater J, Goldstein D, Jensen LH, Klümpen HJ, Lohse AW, Nashan B, Primrose J, Schrum S, Shannon J, Vettorazzi E, Wege H. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015 Jul 31;15:564. doi: 10.1186/s12885-015-1498-0.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 2, 2017)
781
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2014)
450
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

All enrolled patients will postoperatively be assessed for eligibility for the treatment phase. Additionally patients not previously enrolled into the trial for whatever reason (e.g. incidental finding during surgery) will be evaluated for eligibility.

  • Histologically confirmed adenocarcinoma of biliary tract (intrahepatic, hilar or extrahepatic cholangiocarcinoma or muscle invasive gallbladder carcinoma) after radical surgical therapy with macroscopically complete resection (mixed tumor entities (HCC/CCA) are excluded)
  • Macroscopically complete resection (R0/1) within 6 (-16) weeks before scheduled start of chemotherapy
  • ECOG 0-1
  • Age ≥18 years
  • Adequate hematologic function
  • Adequate liver function
  • Adequate renal function
  • No active uncontrolled infection, except chronic viral hepatitis under antiviral therapy
  • No concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to randomization
  • Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women <1 year after the onset of menopause (Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded)

Criteria for initial study enrolment

  • Written informed consent
  • No prior chemotherapy for cholangiocarcinoma
  • No previous malignancy within 3 years or concomitant malignancy, except: non-melanomatous skin cancer or adequately treated in situ cervical cancer
  • No severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia)
  • Absence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent
  • No serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial
  • Fertile women (< 1 year after last menstruation) and procreative men willing and able to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
  • No pregnancy or lactation

Additional eligibility criteria for patients to be included in the radiotherapy substudy:

  • R1 (microscopic positive margin)
  • no previous radiotherapy to abdomen
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexander Stein 004940741056882 a.stein@uke.de
Contact: Jun Li 004940741058572 j.li@uke.de
Listed Location Countries  ICMJE Australia,   Austria,   Denmark,   Germany,   Netherlands,   New Zealand,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02170090
Other Study ID Numbers  ICMJE ACTICCA-1
2012-005078-70 ( EudraCT Number )
ACTRN12615001283561 ( Registry Identifier: ANZCTR (clinical trial registry) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Universitätsklinikum Hamburg-Eppendorf
Study Sponsor  ICMJE Universitätsklinikum Hamburg-Eppendorf
Collaborators  ICMJE
  • Deutsche Krebshilfe e.V., Bonn (Germany)
  • Cancer Research UK
  • Australasian Gastro-Intestinal Trials Group
  • Dutch Cancer Society
Investigators  ICMJE
Principal Investigator: Henning Wege Universitätsklinikum Hamburg-Eppendorf
PRS Account Universitätsklinikum Hamburg-Eppendorf
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP