search
Back to results

Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients

Primary Purpose

Anus Neoplasms, Carcinoma, Squamous Cell, Anus Diseases

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Paclitaxel
Capecitabine
Capecitabine
Mitomycins
Mitomycins
Radiotherapy
Sponsored by
Blokhin's Russian Cancer Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anus Neoplasms focused on measuring anal cancer, chemoradiation, intensity-modulated radiotherapy, paclitaxel

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Informed consent
  • Histologically verified squamous-cell anal cancer
  • Stage I-IIIB (Union for International Cancer Control (UICC) TNM classification v7)
  • Eastern Cooperative Oncology Group (ECOG) status 0-2
  • HIV (Human Immunodeficiency Virus) negative
  • Haemoglobin (HGB) > 90 g/L
  • Platelet Count (PLT) > 120x10*9/L
  • Serum creatinine < 150 µmol/L
  • Total bilirubin < 25 µmol/L

Exclusion Criteria:

  • inability to obtain informed consent
  • distant metastases
  • synchronous or metachronous tumors
  • previous chemotherapy or radiotherapy
  • clinically significant cardiovascular disorders (myocardial infarction < 6 months before visit, stroke < < 6 months before visit, instable angina < 3 months before visit, arrhythmia, uncontrolled hypertension > 160/100 mm hg
  • clinically significant neurological disorders
  • previous neuropathy 2 or higher
  • current infection or heavy systemic disease
  • pregnancy, breastfeeding
  • ulcerative colitis
  • individual intolerance to treatment components
  • proven dihydropyrimidine dehydrogenase (DPD) deficiency
  • participation in other clinical trials
  • psychiatric disorders, which render patient unable to follow instructions or understand his/her condition
  • technical inability to perform pelvic MRI
  • inability of long-term followup of the patient

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Paclitaxel

    Standard

    Arm Description

    Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.

    Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1.

    Outcomes

    Primary Outcome Measures

    3-year disease-free survival

    Secondary Outcome Measures

    Complete response at 26 weeks
    3-year colostomy-free survival
    3-year cancer-specific survival
    3-year overall survival
    Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0
    Toxicity measured according to NCI-CTCAE v.4.0
    Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria
    Late toxicity measured according to RTOG criteria

    Full Information

    First Posted
    August 15, 2015
    Last Updated
    February 7, 2021
    Sponsor
    Blokhin's Russian Cancer Research Center
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT02526953
    Brief Title
    Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients
    Official Title
    Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2021
    Overall Recruitment Status
    Unknown status
    Study Start Date
    January 2016 (undefined)
    Primary Completion Date
    October 2021 (Anticipated)
    Study Completion Date
    October 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Blokhin's Russian Cancer Research Center

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to determine whether the combination of paclitaxel, capecitabine, mitomycin and intensity-modulated radiotherapy is more effective than the standard combination of capecitabine, mitomycin and intensity-modulated radiotherapy (IMRT) in patients with squamous-cell anal cancer.
    Detailed Description
    This trial aims to investigate the efficacy of chemoradiotherapy with or without paclitaxel in squamous-cell anal cancer. This is a prospective multicenter open-label randomized phase III clinical trial. Patients will be randomized using an online randomization system to receive either standard IMRT with capecitabine and mitomycin or IMRT with capecitabine, mitomycin and paclitaxel. A stratification will be performed based on T stage, N stage and clinical center. Doses of capecitabine and mitomycin in experimental group were reduced for better treatment tolerance. The target accrual is 157 patients in each treatment arm (including 10% potential data loss) based on potential benefit of 15% 3-yr disease-free survival (70% vs 85%), α=0,05, power 80% in the experimental arm. An interim analysis is planned after 50% of the patients will reach a 3-year followup. Pelvic Magnetic Resonance Imaging (MRI) is performed in all patients for staging and followup. Pelvic MRI and histological diagnosis are subject to central review. Conduction of this study and data collection are controlled by a local institutional board.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Anus Neoplasms, Carcinoma, Squamous Cell, Anus Diseases, Neoplasms, Neoplasms, Squamous Cell, Carcinoma
    Keywords
    anal cancer, chemoradiation, intensity-modulated radiotherapy, paclitaxel

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    314 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Paclitaxel
    Arm Type
    Experimental
    Arm Description
    Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of paclitaxel 45 mg/m2 on days 3,10,17,24,31, capecitabine 625 mg/m2 bid on treatment days and mitomycin C 10 g/m2 on day 1.
    Arm Title
    Standard
    Arm Type
    Active Comparator
    Arm Description
    Patients will receive intensity-modulated radiotherapy with dose based on T stage. The planned doses to the primary tumor and pelvis are 52-58 Gy and 44 Gy, respectively.The concurrent chemotherapy regimen will consist of capecitabine 825 mg/m2 bid on treatment days and mitomycin C 12 g/m2 on day 1.
    Intervention Type
    Drug
    Intervention Name(s)
    Paclitaxel
    Other Intervention Name(s)
    (2α,4α,5β,7β,10β,13α)-4,10-bis(acetyloxy)-13-{[(2R,3S)- 3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}- 1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate
    Intervention Description
    45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.
    Intervention Type
    Drug
    Intervention Name(s)
    Capecitabine
    Other Intervention Name(s)
    Xeloda
    Intervention Description
    625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
    Intervention Type
    Drug
    Intervention Name(s)
    Capecitabine
    Other Intervention Name(s)
    Xeloda
    Intervention Description
    825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
    Intervention Type
    Drug
    Intervention Name(s)
    Mitomycins
    Other Intervention Name(s)
    Mitomycin C, MMC
    Intervention Description
    10 mg/m2, IV, on day 1. Number of infusions: 1.
    Intervention Type
    Drug
    Intervention Name(s)
    Mitomycins
    Other Intervention Name(s)
    Mitomycin C, MMC
    Intervention Description
    12 mg/m2, IV, on day 1. Number of infusions: 1.
    Intervention Type
    Radiation
    Intervention Name(s)
    Radiotherapy
    Intervention Description
    Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage
    Primary Outcome Measure Information:
    Title
    3-year disease-free survival
    Time Frame
    3 years
    Secondary Outcome Measure Information:
    Title
    Complete response at 26 weeks
    Time Frame
    26 weeks
    Title
    3-year colostomy-free survival
    Time Frame
    3 years
    Title
    3-year cancer-specific survival
    Time Frame
    3 years
    Title
    3-year overall survival
    Time Frame
    3 years
    Title
    Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0
    Description
    Toxicity measured according to NCI-CTCAE v.4.0
    Time Frame
    30 days
    Title
    Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria
    Description
    Late toxicity measured according to RTOG criteria
    Time Frame
    3 years
    Other Pre-specified Outcome Measures:
    Title
    Quality of life according to European organization for research and treatment of cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 (v.3) scale
    Description
    Change from baseline in quality of life on the EORTC QLQ-C30 (v.3) scale
    Time Frame
    3 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Informed consent Histologically verified squamous-cell anal cancer Stage I-IIIB (Union for International Cancer Control (UICC) TNM classification v7) Eastern Cooperative Oncology Group (ECOG) status 0-2 HIV (Human Immunodeficiency Virus) negative Haemoglobin (HGB) > 90 g/L Platelet Count (PLT) > 120x10*9/L Serum creatinine < 150 µmol/L Total bilirubin < 25 µmol/L Exclusion Criteria: inability to obtain informed consent distant metastases synchronous or metachronous tumors previous chemotherapy or radiotherapy clinically significant cardiovascular disorders (myocardial infarction < 6 months before visit, stroke < < 6 months before visit, instable angina < 3 months before visit, arrhythmia, uncontrolled hypertension > 160/100 mm hg clinically significant neurological disorders previous neuropathy 2 or higher current infection or heavy systemic disease pregnancy, breastfeeding ulcerative colitis individual intolerance to treatment components proven dihydropyrimidine dehydrogenase (DPD) deficiency participation in other clinical trials psychiatric disorders, which render patient unable to follow instructions or understand his/her condition technical inability to perform pelvic MRI inability of long-term followup of the patient
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Arsen O Rasulov, PhD
    Organizational Affiliation
    N.N.Blokhin Russian Cancer Research Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Efficacy Study of Chemoradiotherapy With or Without Paclitaxel in Squamous-cell Anal Carcinoma Patients

    We'll reach out to this number within 24 hrs