Trial Outcomes & Findings for Bevacizumab With Pelvic Radiotherapy And Primary Chemotherapy in Patients With Poor-Risk Rectal Cancer (NCT NCT01481545)

Results Overview

Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage. Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

In 8 weeks after completion of chemoradiotherapy

Results posted on

2021-02-03

Participant Flow

Participant milestones

Participant milestones
Measure	Concomitant - Schedule A Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Overall Study STARTED	16	46
Overall Study COMPLETED	11	40
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Concomitant - Schedule A n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).	Total n=62 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	61 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	18 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	28 Participants n=7 Participants	37 Participants n=5 Participants
Race/Ethnicity, Customized Italian	16 Participants n=5 Participants	46 Participants n=7 Participants	62 Participants n=5 Participants
Region of Enrollment Italy	16 Participants n=5 Participants	46 Participants n=7 Participants	62 Participants n=5 Participants
Distance of mesorectal Fascia (MRF) < 5 mm	13 Participants n=5 Participants	35 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: In 8 weeks after completion of chemoradiotherapy

Complete tumor regression rate (TRG1) was the ratio of patients with TRG1, graded at surgical resection, and total patients included in the study, expressed in percentage. Tumor regression grade (TRG) was misured according to the Mandard Scale. Briefly,TRG1 was a complete tumor regression (regardless of the presence of acellular mucine lakes), and TRG2 was a nearly complete tumor regression with extensive fibrosis; TRG3 presented with clear evidence of residual cancer cells but with predominant fibrosis;TRG4 was a residual of cancer cells outgrowing fibrosis; TRG5 was the absence of regressive changes.

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Percentage of Patients With Complete Tumor Regression Rate (TRG1)	12.5 percentage of participants	50 percentage of participants

SECONDARY outcome

Timeframe: Up to 8 weeks after surgery

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Number of Participants With Adverse Events	7 Participants	22 Participants

SECONDARY outcome

Timeframe: In 8 weeks after chemoradiation therapy

Sphincter preservation in patients with tumor \< 5 cm from anal verge in 8 weeks after chemoradiation therapy

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Number of Patients With Sphincter Preservation	13 Participants	41 Participants

SECONDARY outcome

Timeframe: 10 years

Population: PFS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated.

PFS was calculated from the date of the initial treatment until tumor progression or relapse, death for any cause or last follow up. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Progression Free Survival (PFS)	37 participants	11 participants

SECONDARY outcome

Timeframe: 10 years

Population: OS for the schedule A was not calculated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested and, consequently, the accrual was early terminated.

OS was calculated from the date of initial treatment to the date of death for any cause or last follow up.

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Overall Survival (OS)	40 participants	11 participants

SECONDARY outcome

Timeframe: 7 weeks after chemoradiation therapy up to 11 weeks

Clinical response was assessed before surgery with the same imaging modalities that were used for the inclusion in the study. Clinical response rate was the ratio between complete and partial response, evaluated by RECIST CRITERIA, and total of patients evaluated, expressed in percentage of patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Clinical Response Rate	40 percentage of participants	20 percentage of participants

SECONDARY outcome

Timeframe: In 8 weeks after chemoradiation therapy completion

Number of patients with metastatic lymphnodes at pathology exam after surgery.

Outcome measures

Outcome measures
Measure	Concomitant - Schedule A n=46 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=16 Participants Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Patients With Metastatic Lymphnodes at Pathology Exam After Surgery	14 participants	5 participants

Adverse Events

Concomitant - Schedule A

Serious events: 7 serious events

Other events: 7 other events

Deaths: 5 deaths

Sequential - Schedule B

Serious events: 14 serious events

Other events: 22 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Concomitant - Schedule A n=16 participants at risk Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 participants at risk Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Blood and lymphatic system disorders Neutropenia	43.8% 7/16 • 5 years	30.4% 14/46 • 5 years

Other adverse events

Other adverse events
Measure	Concomitant - Schedule A n=16 participants at risk Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemoradiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A)	Sequential - Schedule B n=46 participants at risk Preoperative radiation therapy and combination chemotherapy plus bevacizumab Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B).
Gastrointestinal disorders Diarrhoea	37.5% 6/16 • 5 years	34.8% 16/46 • 5 years
Gastrointestinal disorders Nausea/Vomiting	43.8% 7/16 • 5 years	47.8% 22/46 • 5 years
Gastrointestinal disorders Proctitis	25.0% 4/16 • 5 years	30.4% 14/46 • 5 years
General disorders Asthenia	25.0% 4/16 • 5 years	21.7% 10/46 • 5 years
Blood and lymphatic system disorders Hypertension	25.0% 4/16 • 5 years	23.9% 11/46 • 5 years
Blood and lymphatic system disorders Neutropenia	43.8% 7/16 • 5 years	19.6% 9/46 • 5 years

Additional Information

Dr. Antonio Avallone

National Cancer Institute of Naples

Phone: +39 081 5903629

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place