A Study of Bevacizumab (Avastin) in Participants With Newly Diagnosed Locally Advanced Rectal Cancer

Rectal Cancer Clinical Trial

— INOVA  

Official title:

Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in Locally Advanced Resectable Rectal Cancer: A Randomized, Non-Comparative Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00865189
• Other study ID #: ML19202
• Secondary ID: 2006-003472-35
• Status: Completed
• Phase: Phase 2
• First received: March 18, 2009
• Last updated: July 31, 2017
• Start date: October 23, 2007
• Est. completion date: March 23, 2016

Study information

• Verified date: July 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of two different neoadjuvant treatment approaches including bevacizumab in newly diagnosed participants with high risk locally advanced rectal cancer. Participants will be randomized into one of two treatment arms (Arm A or Arm B).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: March 23, 2016
• Est. primary completion date: March 23, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• histologically confirmed locally advanced rectal cancer;

• measurable disease;

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Exclusion Criteria:

• prior treatment with bevacizumab;

• prior radiotherapy to pelvic region, or previous cytotoxic chemotherapy;

• previous history of malignancy (other than basal and squamous cell cancer of the skin, or in situ cancer of the cervix);

• history or evidence of central nervous system (CNS) disease;

• clinically significant cardiovascular disease;

• chronic treatment with high dose aspirin (more than [>] 325 milligrams per day [mg/day]) or non-steroidal anti-inflammatory drugs.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab will be administered at the fixed dose of 5 milligrams per kilogram (mg/kg) as an IV infusion over 30 to 90 minutes.
• Oxaliplatin
Oxaliplatin will be administered at a dose of 85 milligrams per square meter (mg/m^2) as a 2-hour IV infusion.
• Folinic Acid
Folinic acid will be administered at a dose of 200 mg/m^2 as a 2-hour infusion.
• 5-fluorouracil
5-fluorouracil will be administered at a dose of 400 mg/m^2 as an IV bolus, then at a dose of 600 mg/m^2 as a continuous infusion for 22 hours in Phase 1, and will be administered at a dose of 225 mg/m^2 as a 24-hour infusion, 5 days a week, for 5 weeks in Phase 2.

Radiation:
• Preoperative Radiotherapy
Radiotherapy will be delivered in fraction of 1.8 gray per day (Gy/day), 5 days a week for 5 weeks, i.e., a total dose of 45 Gy will be administered in 25 fractions over a period of 33 days.

Procedure:
• Surgery
Radical rectal excision based on the TME technique.

Locations

Country	Name	City	State
France	ICO Paul Papin; Oncologie Medicale.	Angers
France	HOPITAL JEAN MINJOZ; Oncologie	Besancon
France	Hopital Saint Andre; Département de Radiothérapie Et D'Oncologie Médicale	Bordeaux
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Hopital Albert Michallon; Radiotherapie	La Tronche
France	Centre Oscar Lambret; Radiotherapie	Lille
France	Centre Hospitalier Andre Boulloche; Departement D'Oncologie	Montbeliard
France	Centre Val Aurelle Paul Lamarque; Radiotherapie	Montpellier
France	Polyclinique Gentilly; CHIMIOTHERAPIE AMBULATOIRE	Nancy
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	Ch Pitie Salpetriere; Oncologie Medicale	Paris
France	Hopital Saint Louis; Radiotherapie Oncologie	Paris
France	HOPITAL TENON; Cancerologie Medicale	Paris
France	Ch Lyon Sud; Radiotherapie Sct Jules Courmont	Pierre Benite
France	Chu La Miletrie; Radiotherapie	Poitiers
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	Polyclinique Du Parc; Centre De Hautes Energies	Toulouse
France	Hopital Bretonneau; Clinique D'Oncologie & de Radiotherapie	Tours
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre Les Nancy

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Tumor Sterilization Defined by ypT0-N0	Tumor sterilization was defined as the absence of residual tumor cells in the resected specimen including lymph nodes (ypT0-N0). The rate of sterilization of the tumoral specimen was assessed after surgery on the surgical specimen by local review. Analyses were performed for participants who have been operated as defined by the protocol (within the study and TME technique) and for all participants who have been operated. Reported is the percentage of participants with tumor sterilization.	After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Secondary	Percentage of Participants With Tumor Down-Staging (ypT0-pT2)	A participant with a downstaging was defined as a participant with T3 (T describes the size of the original [primary] tumor) at inclusion and T2 or T1 or T0 after surgery, or with N+ (N describes lymph nodes involvement) at inclusion and N- after surgery and if T is equal at inclusion and after surgery. The clinical tumor-node-metastasis (cTNM) classification was used at inclusion and the pathological staging tumor and nodes (ypTN) classification after surgery. Reported is the percentage of participants with tumor downstaging of the surgical specimen according to the local review and centralized review.	After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Secondary	Percentage of Participants With Local and Distant Recurrences	The percentage of participants with a recurrence was described by type of recurrence (local and distant recurrence).	After surgery (Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment)
Secondary	Percentage of Participants With Second Cancer, Local or Regional Recurrence, Distant Metastasis, or Death		Baseline up to approximately 6 years
Secondary	Disease-Free Survival (DFS)	The DFS was defined as the time from the first treatment intake to disease recurrence assessed (second primary cancer, local or distant recurrence, distant metastases) or death from any cause. The DFS was analyzed using Kaplan-Meier method.	From first time of the treatment administration to the date of second cancer, local or regional recurrence, distant metastasis or death from any cause (up to approximately 6 years)
Secondary	Percentage of Participants Who Died		Baseline up to approximately 6 years
Secondary	Overall Survival	The overall survival was defined as the time from the first treatment intake to death from any cause.	From the first treatment administration to the date of death (up to approximately 6 years)
Secondary	Number of Cycles of Induction Chemotherapy		6 cycles (12 weeks; cycle length = 14 days)
Secondary	Number of Cycles of Chemotherapy		Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Secondary	Number of Cycles of Radiotherapy		Arm A: Week 16 to Week 23; Arm B: Week 1 to Week 7
Secondary	Percentage of Participants With Surgery	The surgery involving a radical rectal excision using the TME technique.	Arm A: approximately 28-31 weeks after initiation of treatment; Arm B: approximately 13-15 weeks after initiation of treatment