Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

NCT01871571 | Unknown Phase 2 DMC FDA Drug

• 4 other identifiers: 3R-12-2NCI-2013-01069ML28263P30CA014089
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well bevacizumab, fluorouracil, leucovorin calcium, and oxaliplatin before surgery works in treating patients with stage II-III rectal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with fluorouracil, leucovorin calcium, and oxaliplatin may be an effective treatment for rectal cancer.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Rate of CPR in the pathology specimen

  Up to 3 years

Secondary Outcomes (5)

• Tumor regression on mesorectal margins (pathologic stage lower than clinical stage)

  Up to 3 years

• Rate of locoregional recurrence

  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)

  Up to 3 years

• Incidence and nature of serious AEs (SAEs) according to NCI CTCAE v4.0

  Up to 3 years

• Incidence and nature of AEs of special interest for bevacizumab (grades) according to NCI CTCAE v4.0

  Up to 3 years

Study Arms (1)

Treatment (bevacizumab, mFOLFOX7)

EXPERIMENTAL

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.

Biological: bevacizumab; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis

Interventions

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Treatment (bevacizumab, mFOLFOX7)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (bevacizumab, mFOLFOX7)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (bevacizumab, mFOLFOX7)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (bevacizumab, mFOLFOX7)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (bevacizumab, mFOLFOX7)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the rectum in patients with no prior therapy who are candidate for surgical resection
• Tumor lesion is 5-15 cm from anal verge
• cT2 N+ or cT3-T4 N0 or N+ as assessed by endorectal ultrasound scan (US)
• No evidence of distant metastatic disease
• Signed informed consent prior to initiation of any study-specific procedure or treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Able to comply with the protocol, including tissue sampling, imaging studies and surgical intervention
• Life expectancy more than 12 weeks
• Absolute neutrophil count \>= 1500 per mm\^3
• Platelet count \>= 100,000 per mm\^3
• Hemoglobin \>= 9 g/dL (may be transfused to maintain or exceed this level)
• Total bilirubin \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase and alanine aminotransferase \< 2.5 x ULN
• Calculated creatinine clearance according to Cockroft and Gault formula \>= 50 mL/min
• Urine for proteinuria should be \< 2 +; patients discovered to have \>= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours

You may not qualify if:

• Prior chemotherapy or radiotherapy for colorectal cancer
• Clinical evidence of bleeding diathesis or coagulopathy
• Pregnancy or lactation
• Sensory peripheral neuropathy \>= grade 2
• Known positivity for human immunodeficiency virus (HIV)
• Malignancies other than rectal cancer within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
• Radiotherapy to any site for any reason within 28 days prior to study entry
• Treatment with any other investigational agent, or participation in another investigational drug trial within 28 days prior to randomization
• Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding, or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of bevacizumab or puts the patient at high risk for treatment-related complications
• Surgery (including open biopsy), significant traumatic injury within 28 days prior to randomization, minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion is allowed
• Current or recent (within 10 days prior to first dose of bevacizumab) use of aspirin (\> 325 mg/day)
• History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding
• Inadequately controlled hypertension (blood pressure: systolic \> 150 mmHg and/or diastolic \> 100 mmHg)
• Clinically significant (i.e., active) cardiovascular disease (e.g., cerebrovascular accident or myocardial infarction within 6 months prior to randomization), unstable angina, congestive heart failure (New York Heart Association Class \>= II) or serious cardiac arrhythmia that is uncontrolled by medication or may interfere with administration of study treatment
• Serious non-healing wound, active peptic ulcer, or untreated bone fracture

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• Barzi A, Choi A, Tsao-Wei D, Iqbal S, El-Khoueiry A, Agafitei DR, Cologne KG, Lenz HJ. Phase II Trial of Neoadjuvant Bevacizumab with Modified FOLFOX7 in Patients with Stage II and III Rectal Cancer. Oncologist. 2020 Dec;25(12):e1879-e1885. doi: 10.1634/theoncologist.2020-0642. Epub 2020 Aug 27.

  PMID: 32649004 DERIVED

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Afsaneh Barzi

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: June 6, 2013
• Study Start: August 2, 2013
• Primary Completion: June 24, 2022
• Study Completion: June 24, 2023
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

US (1)