Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer
|Mucinous Adenocarcinoma of the Rectum Signet Ring Adenocarcinoma of the Rectum Stage IIA Rectal Cancer Stage IIB Rectal Cancer Stage IIC Rectal Cancer Stage IIIA Rectal Cancer Stage IIIB Rectal Cancer Stage IIIC Rectal Cancer||Biological: bevacizumab Drug: oxaliplatin Drug: leucovorin calcium Drug: fluorouracil Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Trial Of Neoadjuvant Bevacizumab With Modified FOLFOX7 In Patients With Stage II And III Rectal Cancer|
- Rate of CPR in the pathology specimen [ Time Frame: Up to 3 years ]
- Tumor regression on mesorectal margins (pathologic stage lower than clinical stage) [ Time Frame: Up to 3 years ]
- Rate of locoregional recurrence [ Time Frame: Up to 3 years ]
- Incidence and nature of adverse events (AEs) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 ( v4) [ Time Frame: Up to 3 years ]
- Incidence and nature of serious AEs (SAEs) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ]
- Incidence and nature of AEs of special interest for bevacizumab (grades) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ]
|Actual Study Start Date:||August 2, 2013|
|Estimated Study Completion Date:||August 2, 2019|
|Estimated Primary Completion Date:||August 2, 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (bevacizumab, mFOLFOX7)
Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV continuously over 46-48 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after treatment, patients undergo surgery.
Other Names:Drug: oxaliplatin
Other Names:Drug: leucovorin calcium
Other Names:Drug: fluorouracil
Other Names:Other: laboratory biomarker analysis
I. To determine if six cycles of modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX7) plus bevacizumab (Avastin) will yield complete pathologic response (cPR) of 25% or more in the primary tumor of patients with stage II and III rectal cancer.
I. To assess the rate of tumor regression (pathologic stage lower than clinical stage) after 6 cycles of mFOLFOX7 and bevacizumab in the primary rectal cancer.
II. To assess local recurrence rate over 3 years after 6 cycles of mFOLFOX7 and bevacizumab.
I. Correlation of the following marker with response (defined as CPR or down staging):
- Intratumoral Gene expression and germline polymorphism of genes involved in the vascular endothelial growth factor (VEGF) and VEGF independent pathways (VEGF, vascular endothelial growth factor receptor 1 [VEGFR1], VEGFR2, interleukin-8 [IL8], chemokine (C-X-C motif) receptor 2 [CXCR2], intercellular adhesion molecule [ICAM], VEGFR1 and VEGFR2, neuropilin 1 or 2 [NRP1,2], cluster of differentiation [CD] 44, aldehyde dehydrogenase [ALDH], leucine-rich repeats and immunoglobulin-like [LRIG].
- Circulating tumor cells (CTC) and VEGF-factor A (A) on the CTC.
II. Prediction of surgical resection margin by pretreatment magnetic resonance imaging (MRI).
Patients receive bevacizumab intravenously (IV) over 30-90 minutes, oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV continuously over 46-48 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Within 6-8 weeks after treatment, patients undergo surgery.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01871571
|Contact: Zeno Ashaifirstname.lastname@example.org|
|United States, California|
|USC Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Dana Agafitei 323-865-0467 Raluca.Agafitei@med.usc.edu|
|Principal Investigator: Afsaneh Barzi|
|Principal Investigator:||Afsaneh Barzi||University of Southern California|