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

NCT01843452 | Terminated Phase 2

• 1 other identifier: CHUV 20080214
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Carcinoma of Anal Canal

Outcome Measures

Primary Outcomes (1)

• Efficacy

  2-year locoregional control in patients, which is defined as the absence of locoregional recurrence 2 years after treatment start.

Secondary Outcomes (7)

• Complete response (CR) rate

  5 years

• Colostomy-free survival

  2 and 5 years

• Functional colostomy-free survival

  2 and 5 years

• Overall survival (OS)

  2 and 5 years

• Progression-free survival (PFS)

  2 and 5 years

Study Arms (1)

Capecitabine, mitomycin, panitumumab and radiotherapy

EXPERIMENTAL

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; Biological: PANITUMUMAB; Drug: MITOMYCIN; Drug: CAPECITABINE

Interventions

RADIOTHERAPY RADIATION

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.

Capecitabine, mitomycin, panitumumab and radiotherapy

PANITUMUMAB BIOLOGICAL

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

Capecitabine, mitomycin, panitumumab and radiotherapy

MITOMYCIN DRUG

10 mg/m2 IV administered over 15 min infusion on days 1 and 29.

Capecitabine, mitomycin, panitumumab and radiotherapy

CAPECITABINE DRUG

825mg/m2 orally twice daily on study days 1 through 45.

Capecitabine, mitomycin, panitumumab and radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (4)

Inselspital

Bern, 3010, Switzerland

Location

Hôpitaux Universitaires de Genève (HUG)

Geneva, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Hôpital du Valais (RSV)

Sion, Switzerland

Location

MeSH Terms

Conditions

Anal Canal Carcinoma

Interventions

Radiotherapy; Panitumumab; Mitomycin; Capecitabine

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Oscar Matzinger, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Physician & senior lecturer

Study Record Dates

• First Submitted: April 26, 2013
• First Posted: April 30, 2013
• Study Start: December 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 19, 2016

Record last verified: 2016-05

Locations

CH (4)