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

Sponsor

Blokhin's Russian Cancer Research Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT02526953

Collaborator

(none)

314

Enrollment

Arms

Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Anus Neoplasms Carcinoma, Squamous Cell Anus Diseases Neoplasms Neoplasms, Squamous Cell Carcinoma	Drug: Paclitaxel Drug: Capecitabine Drug: Capecitabine Drug: Mitomycins Drug: Mitomycins Radiation: Radiotherapy	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

314 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomised Phase III Trial of Chemoradiotherapy With or Without Paclitaxel in Patients With Squamous-cell Anal Cancer

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

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.

Drug: Paclitaxel

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

Other 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

Drug: Capecitabine

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

Other Names:

Xeloda

Drug: Mitomycins

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

Other Names:

Mitomycin C

MMC

Radiation: Radiotherapy

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

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.

Drug: Capecitabine

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

Other Names:

Xeloda

Drug: Mitomycins

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

Other Names:

Mitomycin C

MMC

Radiation: Radiotherapy

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

Outcome Measures

Primary Outcome Measures

3-year disease-free survival [3 years]

Secondary Outcome Measures

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

Other Outcome Measures

Quality of life according to European organization for research and treatment of cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 (v.3) scale [3 years]
Change from baseline in quality of life on the EORTC QLQ-C30 (v.3) scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts 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