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

NCT ID: NCT02526953

Last Updated: 2021-02-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 314 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2022-10-31

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.

Conditions

Anus Neoplasms; Carcinoma, Squamous Cell; Anus Diseases; Neoplasms; Neoplasms, Squamous Cell; Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.

Capecitabine

Intervention Type: DRUG

625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

Mitomycins

Intervention Type: DRUG

10 mg/m2, IV, on day 1. Number of infusions: 1.

Radiotherapy

Intervention Type: RADIATION

Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage

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.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

Mitomycins

Intervention Type: DRUG

12 mg/m2, IV, on day 1. Number of infusions: 1.

Radiotherapy

Intervention Type: RADIATION

Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage

Interventions

Paclitaxel

45 mg/m2, IV, weekly during the radiation. Number of infusions: 5.

Intervention Type: DRUG

Capecitabine

625 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

Intervention Type: DRUG

Capecitabine

825 mg/m2, bid, per os, only on days of radiation (Monday through Friday)

Intervention Type: DRUG

Mitomycins

10 mg/m2, IV, on day 1. Number of infusions: 1.

Intervention Type: DRUG

Mitomycins

12 mg/m2, IV, on day 1. Number of infusions: 1.

Intervention Type: DRUG

Radiotherapy

Dose: 44 Gy on regional nodes, 52-58 Gy on primary tumor, based on T stage

Intervention Type: RADIATION

Other Intervention Names

(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; Xeloda; Xeloda; Mitomycin C; MMC; Mitomycin C; MMC

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Blokhin's Russian Cancer Research Center

OTHER

Sponsor Role: lead

Responsible Party

Sergey Gordeyev

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arsen O Rasulov, PhD

Role: STUDY_CHAIR

N.N.Blokhin Russian Cancer Research Center

Other Identifiers

SCAC-001

Identifier Type: -

Identifier Source: org_study_id