Trial record 1 of 1 for:    NCT01871571
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Bevacizumab, Fluorouracil, Leucovorin Calcium, and Oxaliplatin Before Surgery in Treating Patients With Stage II-III Rectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Southern California
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01871571
First received: June 4, 2013
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Rate of CPR in the pathology specimen [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor regression on mesorectal margins (pathologic stage lower than clinical stage) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Rate of locoregional recurrence [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Incidence and nature of serious AEs (SAEs) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Incidence and nature of AEs of special interest for bevacizumab (grades) according to NCI CTCAE v4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 43
Study Start Date: July 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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).

OUTLINE:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • International normalized ratio =< 1.5 and activated prothrombin time =< 1.5 x ULN within 7 days prior to enrollment; the use of full-dose oral or parenteral anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment
  • Female patients should not be pregnant or breast-feeding. Female patients, if not postmenopausal (< 12 months of amenorrhea) or surgically sterile, should agree to use effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of at least 6 months following the last administration of study drugs. Female patients with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study
  • Fertile male patients must agree to use a highly effective contraceptive method (i.e., with a failure rate of < 1 % per year, such as vasectomy, sexual abstinence, or female partner's use of hormonal implants or combined oral contraceptives) during the trial and for a period of at least 6 months after the last dose of study drug
  • Archival tumor tissue sample must be requested and available prior to study entry; a copy of the local pathology report must be submitted along with the specimens; patients without available archival tissue are excluded

Exclusion Criteria:

  • 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
  • History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months of randomization
  • Known hypersensitivity to bevacizumab or any of its excipients or any other study drug
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01871571

Locations
United States, California
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Catherine Ticong, RN    323-865-0460    catherine.ticong@med.usc.edu   
Principal Investigator: Afsaneh Barzi         
Sponsors and Collaborators
University of Southern California
Investigators
Principal Investigator: Afsaneh Barzi University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01871571     History of Changes
Other Study ID Numbers: 3R-12-2, NCI-2013-01069, ML28263, P30CA014089
Study First Received: June 4, 2013
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Antibodies
Antibodies, Monoclonal
Fluorouracil
Calcium, Dietary
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 20, 2014