Phase II Study of Concomitant Intensity-modulated Radiotherapy Combined to Capecitabine, Mitomycin and Panitumumab in Patients With Stage II-IIIB Squamous-cell Carcinoma of the Anal Canal

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Centre Hospitalier Universitaire Vaudois
Sponsor:
Information provided by (Responsible Party):
Dr Oscar Matzinger, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier:
NCT01843452
First received: April 26, 2013
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

There is increasing evidence of a role of EGFR, treatment with EGFR-inhibitors in anal cancer and synergies of EGFR-inhibitors with radiotherapy. Addition of the human anti-EGFR antibody Panitumumab to chemoradiotherapy seems therefore solidly justified. This trial investigates concurrent panitumumab/capecitabine/mitomycin concurrent to IMRT-radiotherapy. Treatment components used in this study have been selected on scientific rationale. The trial regimen should be feasible with acceptable toxicity and outcome similar to historic series.


Condition Intervention Phase
Carcinoma of Anal Canal
Radiation: RADIOTHERAPY
Biological: PANITUMUMAB
Drug: MITOMYCIN
Drug: CAPECITABINE
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Concomitant Intensity-modulated Radiotherapy Combined to Capecitabine, Mitomycin and Panitumumab in Patients With Stage II-IIIB Squamous-cell Carcinoma of the Anal Canal

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Vaudois:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 2-year locoregional control in patients, which is defined as the absence of locoregional recurrence 2 years after treatment start. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response (CR) rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Tumor assessment will be done by the investigator according to the RECIST 1.1. criteria.

  • Colostomy-free survival [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
    2-year colostomy-free survival (patients without colostomy two-years after treatment start).

  • Functional colostomy-free survival [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
    2-year functional colostomy-free survival (patients without colostomy and without stool incontinence or other sphincter symptoms interfering with activities of daily life two years after treatment start, which correspond to grade 3 toxicity according to common toxicity criteria National Cancer Institute-Common Toxicity Criteria for Adverse Event (NCI-CTCAE) version 4.0.

  • Overall survival (OS) [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
    2-year overall survival (proportion of patients alive two years after treatment start) and median overall survival (median of the interval (days) between treatment start and death for any cause).

  • Progression-free survival (PFS) [ Time Frame: 2 and 5 years ] [ Designated as safety issue: No ]
    2-year PFS (proportion of patients progression-free two years after treatment start) and median PFS according to the RECIST 1.1 criteria. PFS is defined as the interval (days) between registration and the date of progression (based on the actual tumor assessment date), or death for any cause, whichever comes first. The death of a patient without a reported progression will be considered as an event on the date of death. Patients who have neither progressed nor died will be censored on the date of last evaluable tumor assessment. Patients who had no post-baseline assessments and did not have an event will be censored at the time of registration.

  • Tolerability and safety profile of this regimen. [ Time Frame: Early (6 weeks after treatment) and late (up to 2 and 5 years after treatment). ] [ Designated as safety issue: Yes ]
    Toxicities will be assessed according to the NCI-CTCAE (version 4.0).

  • Role of PET for staging and outcome prediction. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Predictive value of PET for PFS. Comparison of PET for determination of complete response with radiologic response and clinical response.


Estimated Enrollment: 65
Study Start Date: December 2012
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Capecitabine, mitomycin, panitumumab and radiotherapy

RADIOTHERAPY: daily fraction dose of 1.8Gy , 5 days a week between day 1 and 45 Intensity modulated radiotherapy (IMRT), using a linac based facility or helical tomotherapy, is obligatory.

The first treatment sequence consists of a total dose of 36 Gy in 20 daily fractions of 1.8 Gy on five days a week.

The second treatment sequence consists of a total dose of 23.4 Gy in 13 daily fractions of 1.8 Gy on five days a week.

PANITUMUMAB: 6 mg/kg IV over 60 min infusion on days 1, 15 and 29

MITOMYCIN: 10 mg/m2 IV over 15 min infusion on days 1 and 29

CAPECITABINE: 825 mg/m2 oral twice daily on days 1 to 45

Radiation: RADIOTHERAPY

External beam radiotherapy (daily fraction dose 1.8Gy) on Monday through Friday starting on study day 1.

  • Days 1-28, dose of 36 Gy in 1.8 Gy/fraction (20 fractions) to the clinical target volume 1 (CTV1) including the primary tumor and involved lymph nodes and areas at risk for metastatic spread (which includes gross tumour volumes (GTV) and a 1-cm expansion, mesorectal space, inguinal, femoral, external iliac, internal iliac, and common iliac vessels).
  • Days 29-45, a boost dose of 23.4 Gy in 1.8 Gy/fraction (13 fractions) to the GTV.
Biological: PANITUMUMAB
6 mg/kg IV administered over 60 min infusion on days 1,15 and 29.
Drug: MITOMYCIN
10 mg/m2 IV administered over 15 min infusion on days 1 and 29.
Drug: CAPECITABINE
825mg/m2 orally twice daily on study days 1 through 45.

Detailed Description:

OBJECTIVES:

Primary:

-To assess efficacy of treatment regimen composed of capecitabine, mitomycin, panitumumab, and radiotherapy in terms of locoregional control rate in patients with stage II-IIIB squamous-cell carcinoma of the anal canal.

Secondary:

  • To further assess efficacy of this regimen based on complete response (CR) rate, colostomy-free survival, functional colostomy-free survival, overall survival (OS), and progression-free survival (PFS).
  • To assess the tolerability and safety profile of this regimen.
  • To assess the role of PET for staging and outcome prediction (for those patients who had PET following local standards).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically/pathologically confirmed squamous-cell carcinoma of the anal canal
  • Stage II-IIIB (T2-4, N any, M0) disease
  • Previously untreated disease
  • Age ≥ 18 years at time of consent
  • Life expectancy of at least 2 years
  • ECOG performance status (PS) of 0 to 1
  • Adequate bone marrow, liver and renal functions as assessed by the following laboratory requirements to be conducted within 14 days prior to registration.

    • Hemoglobin ≥ 90 g/l without transfusion requirement in the prior 4 weeks
    • Absolute neutrophil count (ANC) ≥1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
    • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
    • ALT and AST ≤ 2.5 x ULN
    • Alkaline phosphatase < 4 x ULN
    • PT/PTT < 1.5 x ULN (patients who receive anticoagulation treatment with an agent such as warfarin or heparin will be allowed to participate; for patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at predose, as defined by the local standard of care.
    • Serum creatinine clearance ≤ 1.5 x ULN (≥ 60 ml/min calculated using the Cockcroft-Gault formula)
  • Patients with stable HIV infection (i.e. undetectable viral load over the past 6 months while on HIV treatment and with CD4 count > 200 /ml) can be included.
  • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria:

  • Prior treatment with capecitabine or mitomycin
  • Prior or concurrent chemotherapy, or any antitumoral hormonal therapy
  • Prior treatment with panitumumab or other EGFR inhibitors
  • Prior biologic therapy or immunotherapy, e.g. anti-TNF treatment etc.
  • Less than 24 hours since prior granulocyte colony-stimulating factors
  • Any other concurrent anticancer therapy, including experimental medications
  • Receipt of any investigational agent within 4 weeks of study registration
  • Concurrent alternative medicine, vitamin supplements unless approved by the investigator
  • Prior radiation therapy to the pelvis
  • Prior surgery for anal canal cancer except biopsy
  • Evidence of metastatic disease
  • Prior or concurrent malignancy other than the study disease unless treated with curative intent and with no evidence of disease
  • Any of the following within 6 months prior to study drug administration: severe/ unstable angina (symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction, congestive heart failure, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Known active Hepatitis B or C
  • Active clinically serious infection > NCI-CTCAE v4.0 grade 3
  • Known or suspected allergy to panitumumab or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Symptomatic pulmonary fibrosis
  • History of collagen vascular disease
  • Other severe, acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate contraception during the course of the trial and three months after the completion of trial
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01843452

Locations
Switzerland
Inselspital Recruiting
Bern, Switzerland, 3010
Contact: Evelyn MD Herrmann    +41 31 632 24 31    evelyn.herrmann@insel.ch   
Principal Investigator: Evelyn Herrmann, MD         
Hôpitaux Universitaires de Genève (HUG) Recruiting
Geneva, Switzerland
Contact: Arnaud Roth, MD       Arnaud.Roth@hcuge.ch   
Principal Investigator: Arnaud Roth, MD         
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
Contact: Oscar Matzinger, MD    21 314 46 00 ext 41    oscar.matzinger@chuv.ch   
Principal Investigator: Oscar Matzinger, MD         
Hôpital du Valais (RSV) Recruiting
Sion, Switzerland
Contact: Kaouthar Khanfir, MD       kaouthar.khanfir@hopitalduvalais.ch   
Principal Investigator: Kaouthar Khanfir, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire Vaudois
Investigators
Principal Investigator: Oscar Matzinger, MD Centre Hospitalier Universitaire Vaudois
  More Information

No publications provided

Responsible Party: Dr Oscar Matzinger, Senior Physician & senior lecturer, Centre Hospitalier Universitaire Vaudois
ClinicalTrials.gov Identifier: NCT01843452     History of Changes
Other Study ID Numbers: CHUV 20080214
Study First Received: April 26, 2013
Last Updated: June 18, 2014
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Mitomycins
Mitomycin
Capecitabine
Fluorouracil
Antibodies, Monoclonal
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014