A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.

• ClinicalTrials.gov Identifier: NCT01227707
• Recruitment Status: Completed
• First Posted: October 25, 2010
• Results First Posted: August 15, 2014
• Last Update Posted: August 17, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 22, 2010
• First Posted Date: October 25, 2010
• Results First Submitted Date: May 28, 2014
• Results First Posted Date: August 15, 2014
• Last Update Posted Date: August 17, 2015
• Study Start Date: November 2005
• Actual Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 24, 2014)

Percentage of Participants With Pathological Complete Response (pCR) [ Time Frame: 6 to 8 weeks following completion of neoadjuvant treatment ]

pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected.

• Original Primary Outcome Measures (submitted: October 22, 2010): Pathological complete response rate (pCR) after chemo-radiotherapy (histologic tumour assessment by local and central pathologist) [ Time Frame: approximately 2 years ]
• Change History: Complete list of historical versions of study NCT01227707 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 24, 2014)

• Percentage of Participants by Primary Tumor (T), Regional Lymph Nodes (N), and Distant Metastasis (M) Clinical Stage at Baseline and at the End of Neo-Adjuvant Treatment (NAT) [ Time Frame: Baseline (BL) and end of neoadjuvant treatment (within 6 weeks after the completion of study treatment) ]
  The frequencies of clinical tumor stage T (0, 1, 2, 3, 4, or X), regional lymph nodes stage N (0, 1, 2, 3, or 4), and distant metastasis clinical stage M (0, 1, or X) at baseline and at the end of NAT were assessed. The frequencies of pathological tumor stage T and regional lymph nodes stage N at surgery were evaluated. The clinical tumor and lymph node status was assessed by clinical examination, endosonography, and/or rectosigmoidoscopy, and pelvic and abdomen computerized tomography (CT) scan or magnetic resonance imaging (MRI). Response to treatment had to be assessed within 6 weeks after end of treatment by using the same techniques performed at baseline.
• Percentage of Participants Undergoing Sphincter-Saving Surgery by Type of Procedure [ Time Frame: 6 to 8 weeks after completion of study treatment ]
• Percentage of Participants With Complete Response (CR) at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ]
  Percentage of participants with CR was evaluated as the proportion of participants with complete response for the target and non-target lesions, separately, at the end of NAT according to the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions or all non-target lesions and normalization of tumor marker levels.
• Percentage of Participants With an Overall Response of CR at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ]
  Percentage of participants with an overall response of CR was evaluated as the proportion of participants with CR for the target and non-target lesions plus absence of new lesions at the end of NAT according to RECIST. CR was defined as disappearance of all target lesions, all non-target lesions, and normalization of tumor marker levels.
• Percentage of Participants With New Lesions at the Primary Tumor Site at the End of Neoadjuvant Treatment [ Time Frame: BL and within 6 weeks after the completion of study treatment ]
  The percentage of participants with new lesions located at the primary tumor site were evaluated at the end of NAT.
• Percentage of Participants With Relapse During Follow-Up [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ]
  The percentage of participants with local and/or regional relapse during follow-up. New lesions located at rectum or at colon or at lymph node detected at the end of NAT were evaluated as local and/or regional relapse.
• Disease-Free Survival (DFS) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ]
  DFS was defined as the time from treatment start date to the date of first progression of disease or date of death due to any cause.
• DFS - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until progression, up to 45 months ]
  The time in months from date of start-of-treatment to the date of event defined as the first documented disease progression or death due to any cause. If a participant did not have an event, the time was censored at the date of last adequate tumor assessment. DFS was estimated using the Kaplan-Meier method.
• Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ]
  OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive.
• OS - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ]
  OS was defined as the time from the date of first day of treatment until death due to any cause or the last date the participant was known to be alive. OS was estimated using the Kaplan-Meier method.
• Time to Disease Progression (TTP) - Percentage of Participants With an Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ]
  TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer.
• TTP - Time to Event [ Time Frame: BL, within 6 weeks after the completion of neoadjuvant treatment, every 2 weeks for 1 year following surgery, every 3 months thereafter until death, up to 45 months ]
  TTP was defined as the time from date of treatment start until first documented progression of disease or death due to underlying cancer. TTP was estimated using the Kaplan-Meier method.

Original Secondary Outcome Measures (submitted: October 22, 2010)

• Clinical tumour and lymph node response to chemo-radiotherapy (assessments by endosonography, rectosigmoidoscopy, pelvic and abdomen CT scan or MRI) [ Time Frame: approximately 2 years ]
• Safety: Incidence of adverse events [ Time Frame: approximately 5 years ]
• Sphincter-saving procedure rate after pre-operative chemo-radiotherapy [ Time Frame: approximately 2 years ]
• Disease-free survival (tumor assessments by endosonography, rectosigmodoscopy and pelvic and abdomen CT scan or MRI) [ Time Frame: approximately 5 years ]
• Overall survival [ Time Frame: approximately 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer.
• Official Title: An Open-label Study to Assess the Effect of Combination Treatment With Avastin and Xeloda, Plus Pre-operative Standard Radiotherapy, on Response Rate in Patients With Locally Advanced Rectal Cancer.
• Brief Summary: This open-label study will assess the efficacy and safety of Avastin (bevacizumab) plus Xeloda (capecitabine) in combination with standard technique radiotherapy of the pelvic region in the neo-adjuvant setting in patients with locally advanced primary rectal cancer. Patients will receive 4 courses of Avastin at a dose of 5 mg/kg intravenously (iv) every 2 weeks and for 38 days Xeloda at dose of 825 mg/kg twice daily orally, plus radiation therapy. After surgery, adjuvant treatment with 5-fluorouracil/leucovorin and, at the discretion of the investigator, with Avastin 5 mg/kg iv every 2 weeks for at least 6 months will be given.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: bevacizumab [Avastin]
  5 mg/kg intravenously every 2 weeks, 4 cycles
• Drug: capecitabine [Xeloda]
  825 mg/m2 twice daily orally, 38 days
• Radiation: Radiation therapy
  Total dose of 45 Gy over 38 days
• Procedure: Mesorectal excision
  6-8 weeks after completion of neoadjuvant treatment
• Drug: bevacizumab [Avastin]
  Post-surgery adjuvant treatment at the discretion of the investigator: 5 mg/kg iv every 2 weeks for at least 6 months
• Drug: 5-fluorouracil
  Post-surgery adjuvant therapy: bolus of 400mg/m2 iv plus iv infusion of 600 mg/m2 on Days 1 and 2 of each 2-week cycle for 6 months
• Drug: leucovorin
  Post-surgery adjuvant treatment: 100 mg/m2 iv on Days 1 and 2 of each 2-week cycle for 6 months

Study Arms

Experimental: Single Arm

Interventions:

• Drug: bevacizumab [Avastin]
• Drug: capecitabine [Xeloda]
• Radiation: Radiation therapy
• Procedure: Mesorectal excision
• Drug: bevacizumab [Avastin]
• Drug: 5-fluorouracil
• Drug: leucovorin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 22, 2010): 43
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2010
• Actual Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult patients, >=18 years of age
• Patients with confirmed rectal cancer who are subject to surgery and would benefit from pre-operative combined chemo-radiotherapy
• Measurable and/or evaluable lesions according to RECIST criteria
• EOCG performance status 0-1

Exclusion Criteria:

• Prior radiotherapy or chemotherapy for rectal cancer
• Untreated brain metastases or spinal cord compression or primary brain tumors
• Chronic daily treatment with high-dose aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration
• Co-existing malignancies, or malignancies diagnosed within the last 5 years, with the exception of basal and squamous cell cancer, or cervical cancer in situ.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT01227707
• Other Study ID Numbers: ML18522
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Not Provided

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: July 2015