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

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Southern California
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Bevacizumab; Calcium, Dietary; Fluorouracil; Immunoglobulins; Leucovorin; Levoleucovorin; Oxaliplatin

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