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

Overview

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.

Full Title of Study: “Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2021

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.

Interventions

  • Drug: Paclitaxel
    • 45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.
  • Drug: Capecitabine
    • 625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
  • Drug: Capecitabine
    • 825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)
  • Drug: Mitomycins
    • 10 mg/m2, IV, on day 1. Number of infusions: 1.
  • Drug: Mitomycins
    • 12 mg/m2, IV, on day 1. Number of infusions: 1.
  • Radiation: Radiotherapy
    • Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage

Arms, Groups and Cohorts

  • Experimental: Paclitaxel
    • 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.
  • Active Comparator: Standard
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 3-year disease-free survival
    • Time Frame: 3 years

Secondary Measures

  • Complete response at 26 weeks
    • Time Frame: 26 weeks
  • 3-year colostomy-free survival
    • Time Frame: 3 years
  • 3-year cancer-specific survival
    • Time Frame: 3 years
  • 3-year overall survival
    • Time Frame: 3 years
  • Acute toxicity measured according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0
    • Time Frame: 30 days
    • Toxicity measured according to NCI-CTCAE v.4.0
  • Late toxicity measured according to Radiation Therapy Oncology Group (RTOG) criteria
    • Time Frame: 3 years
    • Late toxicity measured according to RTOG criteria

Participating in This Clinical Trial

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) > 120×10*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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Blokhin’s Russian Cancer Research Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Sergey Gordeyev, Principal Investigator – Blokhin’s Russian Cancer Research Center
  • Overall Official(s)
    • Arsen O Rasulov, PhD, Study Chair, N.N.Blokhin Russian Cancer Research Center

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.