Preoperative Combined Induction Chemotherapy With Capecitabine, Oxaliplatin, Bevacizumab and Radiotherapy

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier:
NCT01434147
First received: September 13, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

Phase II pilot study of a preoperative induction chemotherapy in combination with Bevacizumab followed by combined radiochemotherapy for patients with locally advanced rectal carcinoma


Condition Intervention Phase
Rectal Cancer
Drug: preoperative induction chemotherapy in combination with bevacizumab followed by combined radiochemotherapy with capecitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preoperative Induction Chemotherapy in Combination With Bevacizumab Followed by Combined Chemoradiotherapy in Locally Advanced Rectal Cancer With High Risk of Recurrence- Phase II Pilot Study With Preoperative Administration of Capecitabine (Xeloda), Oxaliplatin and Bevacizumab (Avastin) Followed by Capecitabine (Xeloda) Plus Radiotherapy (RTx)

Resource links provided by NLM:


Further study details as provided by Austrian Breast & Colorectal Cancer Study Group:

Primary Outcome Measures:
  • termination of therapy [ Time Frame: up to 17 weeks ] [ Designated as safety issue: Yes ]
    before surgery (after conclusion of therapy phase)

  • occurence of toxicity [ Time Frame: up to 18-19 weeks ] [ Designated as safety issue: Yes ]
    until timepoint of discharge of patient


Secondary Outcome Measures:
  • collection of response rate [ Time Frame: up to week 18 ] [ Designated as safety issue: No ]
    T- and N-downstaging, pathological complete remission: measurement at the timepoint of surgery

  • post-surgery morbidity [ Time Frame: after 18-19 weeks ] [ Designated as safety issue: Yes ]
    according to Accordion; measurement at the timepoint of discharge of patient


Enrollment: 25
Study Start Date: October 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: induction chemotherapy + radiochemotherapy
preoperative induction chemotherapy in combination with bevacizumab followed by combined radiochemotherapy with capecitabine induction chemotherapy: starts within 28 days after bioptical diagnosis. All patients are administered with capecitabine (Xeloda®) 1000 mg/m2 bid during 14 days (d1-d14), oxaliplatin 130 mg/m2 and bevacizumab (Avastin®) 7.5 mg/kg body weight on day 1; repetition days 22 and 43 (3 cycles) Combined radiochemotherapy: starts at the earliest one week after concluded third cycle of induction chemotherapy. Radiotherapy takes place on 5 x 5 days (dose: 1.8 Gy; cumulative dose: 45 Gy). For chemotherapy patients are administered with capecitabine (Xeloda®) 825mg/m² bid, on each radiation day during the first 4 weeks of radiochemotherapy.
Drug: preoperative induction chemotherapy in combination with bevacizumab followed by combined radiochemotherapy with capecitabine
Therapy start: Capecitabine 1000mg/ m² bid during 14 days(d1-14), oxaliplatin 130mg/m² and Bevacizumab 7.5mg/kg body weight d1, repetition day 22 and 43 (3 cycles) Radiotherapy: Followed by 5 x 5 days 1.8 Gy after 1 week of concluded 3rd cycle of induction chemotherapy Chemotherapy: Capecitabine 825 mg/m2 bid (on each therapy day of first 4 therapy weeks)
Other Names:
  • Xeloda (capecitabine)
  • Avastin (bevacizumab)
  • Oxaliplatin

Detailed Description:

Induction chemotherapy combined with Radio chemotherapy:

Therapy start: within 28 days after bioptical diagnosis capecitabine 1000 mg/m2 bid during 14 days (d1-d14) , oxaliplatin 130 mg/m2 and bevacizumab 7.5 mg/kg body weight d1; repetition day 22 and 43 (3 cycles)

Combined Radiochemotherapy after 1 week of concluded 3rd cycle of induction chemotherapy:

Radiotherapy: 5 x 5 days 1.8 Gy; cumulative dose 45 Gy Chemotherapy: capecitabine 825mg/m² bid, on each radiation day during the first 4 weeks of RCTx

Surgery according to TME-criteria (total mesorectal excision) in compliance of an interruption of min. 14 days after RCTx

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-80 years
  • Histologic confirmation of rectal adenocarcinoma stage cT3 (≤ 5mm to the mesorectal fascia)/cT4( primary curative intention)NxM0
  • No former chemotherapy, no former radiotherapy of the pelvic, no former tumour resection of a rectal carcinoma
  • General condition WHO grade 0-2
  • Adequate bone marrow reserve ( leucocytes ≥3 000/μl, thrombocytes ≥100 000/μl)
  • Adequate renal function (creatinine ≤ 1,5 mg/dl, creatinine clearance > 50ml/min (Cockcroft and Gault formula))
  • Adequate liver function (bilirubin ≤1,5x ULN, GOT and GPT ≤3,5xULN)
  • Exclusion of pregnancy for women with childbearing potential (negative pregnancy test urine or serum)
  • Female patients with childbearing potential and male patients that are not surgically sterile must be practicing a medically acceptable contraceptive regimen while on study treatment until 3 months after the end of the study (e.g. oral contraceptives, condom, intrauterine device)
  • Life expectancy of at least 3 months
  • INR and aPTT ≤ 1,5 x LLN
  • Provision of signed informed consents before registration

Exclusion Criteria:

  • Rectal carcinoma stage cT3 (> 5mm from the mesorectal fascia) all stages <cT3, M1
  • Other malignant tumours within the last 5 years except cervical carcinoma in situ and basal cell carcinoma of the skin
  • General contraindication or known hypersensitivity against Bevacizumab, Capecitabine and Oxaliplatin
  • Not malignant diseases for which treatment with radiotherapy, resection of the rectum and treatment with chemotherapy (Bevacizumab, Capecitabine) is contraindicated: uncontrolled hypertension (systolic > 150 mmHG and/or diastolic > 100 mmHG) or clinically significant (e.g. active) cardiovascular diseases: CVA (cardiovascular accident)/ apoplectic insult (≤ 6 months prior to registration), myocardial infarction (≤ 6 months prior to registration), unstable angina pectoris, CHF(congestive heart failure) with NYHA (New York heart Association) Grade II or higher, cardiac arrhythmia requiring therapy, hepatic diseases, significant neurologic or psychiatric disorders
  • Florid, serious infection at registration
  • Peripheral neuropathy (NCI CTCAE v 4.0 ≥ grade 1)
  • Juridically limited contractual capability, indication of neurological or psychiatric disease which constrains upon investigators opinion the patients capability to adhere to the study routines
  • Major surgical procedure within 28 days prior start of the study, open wounds
  • Significant traumatic injury, bone fracture, unhealed wounds
  • Patients with spinal cord compression or metastases in the central nervous system
  • Indication of bleeding diathesis or coagulopathy
  • Intake of anticoagulant or thrombolytic agents and/or Aspirin > 325 mg/d within 10 days prior to registration
  • Current or recent (within 10 days prior to treatment start) therapy with full dosed anticoagulants. Preventive therapy is allowed.
  • Previous thromboembolic or haemorrhagic events within 6 months prior to registration
  • Previous abdominal fistulas, gastro-intestinal perforation or intrabdominal abscesses within 6 months prior to registration
  • Treatment with another investigational drug within 28 days prior to registration
  • Patients with malabsorption syndrome or difficulties in swallowing
  • Indication of poor compliance of the patient
  • Pregnant or breast-feeding women
  • Proteinuria: Dipstick <2+. If the Dipstick is ≥2+ protein has to be estimated in the 24 hours urine. The value should not be higher then 1g/24 hours.
  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: NCT01434147

Locations
Austria
Hospital BHB St. Veit/Glan, Surgery
St. Veit a. d. Glan, Carinthia, Austria, 9330
Medical University Graz, Oncology
Graz, Styria, Austria, 8036
Medical University Innsbruck, Internal Medicine
Innsbruck, Tyrol, Austria, 6020
Klinikum Wels-Grieskirchen
Wels, Upper Austria, Austria, 4600
State Hospital Feldkirch, Radiotherapy
Feldkirch, Vorarlberg, Austria, 6807
Paracelsus Medical University Salzburg - Oncology
Salzburg, Austria, 5020
Medical University of Vienna, General Hospital
Vienna, Austria, 1090
Sponsors and Collaborators
Austrian Breast & Colorectal Cancer Study Group
Hoffmann-La Roche
Investigators
Study Chair: Dietmar Öfner, MD, Head Austrian Breast & Colorectal Cancer Study Group
Study Chair: Alexander de Vries, MD, Head Austrian Breast & Colorectal Cancer Study Group
Study Chair: Wolfgang Eisterer, MD Austrian Breast & Colorectal Cancer Study Group
  More Information

Additional Information:
Publications:
NIH Consensus Conference. JAMA 1990;264:1440-50
Valentini et al. Multidisciplinary rectal cancer management: 2nd European rectal cancer conference (EURECA-CC2). Radiother Oncol 2009;92:148-63
ABCSG gemeinsam mit ACO/ASSO, ÖGC, ÖGHO, ÖGP, ÖGRO, ÖRG1 Empfehlungen zu Diagnostik und multimodaler Primärtherapie des Rektumkarzinoms 2004. WiKliWo 2004;117:154-71.
Dipetrillo et al. Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer. J Clin Oncol 27 (suppl):170s, abstr 4105.
Gerard et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0450-Prodige 2. J Clin Oncol 2010;28:1638-1644
Aschele et al. Oxaliplatin in locally advanced rectal cancer: pathologic response analysis of the studio terapia adiuvante retto (STAR)-01 randomized phase III trial. J Clin Oncol 27 (suppl):170s, abstr CRA4008
S3-Leitlinie "Kolorektales Karzinom, Arbeitsgruppe "Workflow Rektumkarzinom" Zentralbl Chir 2006; 131:285-297

Responsible Party: Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier: NCT01434147     History of Changes
Other Study ID Numbers: ABCSG R05, 2010-024354-11
Study First Received: September 13, 2011
Last Updated: March 6, 2014
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Austrian Breast & Colorectal Cancer Study Group:
locally advanced rectal cancer
preoperative induction chemotherapy chemoradiotherapy

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Capecitabine
Bevacizumab
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014