Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer (BRANCH)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT01481545
First received: November 11, 2011
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to evaluate the use of chemotherapy, radiation therapy and bevacizumab before surgery in patients with locally advanced rectal cancer (LARC).


Condition Intervention Phase
Rectal Cancer
Radiation: Radiation therapy
Drug: Oxaliplatin
Drug: Raltitrexed
Drug: levofolinic acid
Drug: 5-fluorouracil
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer: the BRANCH Trial

Resource links provided by NLM:


Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • complete tumor regression rate (TRG1) [ Time Frame: within 8 weeks after completion of chemoradiotherapy ] [ Designated as safety issue: No ]
    complete tumor regression rate(TRG1) with tumor regression graded at at surgical resection at 8 weeks after completion of chemoradiotherapy


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: every week from start of therapy to 7 weeks after therapy conclusion ] [ Designated as safety issue: Yes ]
  • sphincter saving procedure rate [ Time Frame: 8 weeks after chemoradiation therapy ] [ Designated as safety issue: No ]
  • disease free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • clinical response rate [ Time Frame: 8 weeks after chemoradiation therapy ] [ Designated as safety issue: No ]
  • number of patients with metastaticlymph nodes at pathology exam after surgery [ Time Frame: 8 weeks after chemoradiation therapy completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: December 2006
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: preoperative chemoradiotherapy
Preoperative radiation therapy and combination chemotherapy plus bevacizumab
Radiation: Radiation therapy
Radiation therapy will be administered at the total dose of 45 Gy, given with five weekly fractions over a period of 5 weeks. The daily fraction dose will be 1.8 Gy
Drug: Oxaliplatin
100 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
Drug: Raltitrexed
2.5 mg/m2 on day 1 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1) , an additional 2 cycles of chemotherapy will be given after radiation therapy)
Drug: levofolinic acid
250 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
Drug: 5-fluorouracil
800 mg/m2 on day 2 every 2 weeks for 3 cycles (for patients with resectable organ metastases (M1), an additional 2 cycles of chemotherapy will be given after radiation therapy)
Drug: Bevacizumab
will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage (statistical design) with the classical schedule (for patients with resectable organ metastases (M1), one additional administration of bevacizumab will be given after radiation therapy)

Detailed Description:

To determine the pathological complete response (pCR-TRG1) rate in patients treated with 2 different schedule of bevacizumab plus primary chemotherapy and radiotherapy of the pelvic region when optimal surgery is applied.

Bevacizumab will be given by intravenous infusion at the dose of 5 mg/kg concurrent with chemotherapy and radiotherapy every 2 weeks for 4 cycles from -14 days to start chemo-radiotherapy (classical schedule) or 4 days before the concurrent administration of chemotherapy and radiation therapy for 2 cycles if the number of TRG1 was not reached in the first stage with the classical schedule Simon's methods will be used to calculate sample size.Setting a and b errors as 0.05 and 0.20, respectively, and defining as minimum activity of interest (p0) a TRG1 rate=30%. In order to demonstrate a TRG1 rate ≥50% (p1), at least 6 TRG1 on the first 15 patients, and at least 19 TRG1 on a total of 46 patients should be reported in the first and second stage, respectively.

  Eligibility

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

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed diagnosis of locally advanced rectal cancer (LARC) at high risk of recurrence (T4, N+, T3N0 with tumor located in the lower third of the rectum and/or circumferential resection margin (CRM) £5 mm), or LARC with resectable organ metastasis (M1).
  • Age 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Life expectancy of at least 12 weeks
  • Measurable and/or evaluable (resectable organ metastasis)lesions according to RECIST criteria
  • Neutrophils > 1500 and Platelets > 100,000 /L
  • Total bilirubin < or = 1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) < or = 2.5 x UNL, or < or = 5 x UNL in case of liver metastases, alkaline phosphatase < or = 2.5 x UNL, or < or = 5 x UNL in case of liver metastases.
  • Creatinine clearance > 50 mL/min or serum creatinine < or = 1.5 x UNL
  • Urine dipstick of proteinuria < 2+. Patients discovered to have > or = 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate < or = 1 g of protein/24 hr.
  • Written informed consent.
  • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating Center

Exclusion Criteria:

  • Prior radiotherapy or chemotherapy for rectal cancer.
  • Untreated brain metastases or spinal cord compression or primary brain tumours
  • History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke).
  • History of inflammatory bowel disease and/or acute/subacute bowel occlusion
  • Serious, non-healing wound, ulcer, or bone fracture
  • Evidence of bleeding diathesis or coagulopathy.
  • Uncontrolled hypertension
  • Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
  • Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
  • Chronic, daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration.
  • Treatment with any investigational drug within 30 days prior to enrolment.
  • Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications
  • Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
  • Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
  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: NCT01481545

Sponsors and Collaborators
National Cancer Institute, Naples
Investigators
Principal Investigator: Antonio Avallone, M.D. National Cancer Institute, Naples
  More Information

No publications provided

Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01481545     History of Changes
Other Study ID Numbers: BRANCH, 2008-003989-26
Study First Received: November 11, 2011
Last Updated: July 29, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
locally advanced
high risk
preoperative therapy

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
Fluorouracil
Raltitrexed
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 14, 2014