High-Dose Cholecalciferol in Treating Patients Receiving Combination Chemotherapy and Bevacizumab as First-Line Therapy For Metastatic Colorectal Cancer

NCT01198548 | Terminated Phase 2 Results DMC

• 2 other identifiers: I 176910NCI-2010-01783
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving high-dose cholecalciferol works in treating patients receiving combination chemotherapy and bevacizumab as first-line therapy for metastatic colorectal cancer. Cholecalciferol during treatment may delay the development of colorectal cancer. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving cholecalciferol together with combination chemotherapy and monoclonal antibody therapy may be an effective treatment for colorectal cancer

Conditions

Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Median PFS

  The estimated distributions of PFS will be obtained using the product-limit based Kaplan-Meier method. The corresponding 95% confidence intervals for the estimated probability will be computed using the method proposed in Clopper and Pearson.

  Up to 12 months

• Rate of Sufficient Cholecalciferol

  By week 16

Secondary Outcomes (4)

• RR of Patients Receiving Study Treatment

  Up to 3 years

• Toxicity Rates as Assessed by NCI CTCAE Version 4

  Up to 30 days post-treatment

• OS of Patients Receiving Study Treatment

  Up to 3 years

• PFS of Patients Receiving Study Treatment

  Defined as the time from the start of the study treatment until the date of progression or death from any cause, whichever comes first, assessed up to 3 years

Study Arms (1)

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

EXPERIMENTAL

Patients receive high-dose cholecalciferol once daily. Patients also receive bevacizumab IV over 10 minutes, leucovorin calcium IV over 2 hours, oxaliplatin\* IV over 2 hours, and fluorouracil IV continuously over 46 hours once a week. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: \*Treatment with oxaliplatin is discontinued after course 8

Drug: leucovorin calcium; Biological: bevacizumab; Dietary Supplement: cholecalciferol; Drug: fluorouracil; Drug: oxaliplatin; Other: pharmacological study

Interventions

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

bevacizumab BIOLOGICAL

Given IV

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

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

cholecalciferol DIETARY_SUPPLEMENT

Given PO

Also known as: Calciol, Vitamin D3

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

fluorouracil DRUG

Given IV

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

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

oxaliplatin DRUG

Given IV

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

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (FOLXFOX, bevacizumab, cholecalciferol)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients should have untreated metastatic colorectal cancer; prior adjuvant chemotherapy is allowed as long as the development of metastatic disease occurred more than 6 months from completion of adjuvant treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Platelets \>= 100,000/mm\^3
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• Hemoglobin \> 9 gm/dl
• Calculated creatinine clearance \> 40 ml/min according to the Cockcroft-Gault formula OR per 24 hour urine collection
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5 x institutional upper normal level if no liver metastases and \< 5 x upper limit of normal (ULN) in the setting of liver metastases
• Total bilirubin =\< 1.5 x institutional upper normal level
• Albumin \>= 2.5 g/dl
• Urine protein:creatinine (UPC) ratio \< 1; in the event UPC is \> 1, the patient will require a 24-hr urine protein and will be eligible if 24-hr urine collection has \< 1,000 mg protein
• Patients of child-hearing potential must agree to use acceptable contraceptive methods (e.g., double harrier) during treatment
• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board-approved written informed consent form prior to receiving any study-related procedure
• Presence of measurable disease defined as a lesion \>= 1 cm by computed tomography (CT); all sites of disease should be evaluated =\< 3 weeks before treatment initiation
• Baseline 25-D3 level of \< 40 ng/ml

You may not qualify if:

• Patients may not be receiving any other investigational agents that are not included in this study
• Patients with known brain metastases
• History of other invasive cancers with the exception of the following: a. Curatively resected or treated non-melanoma skin cancer; b. Curatively treated cervical carcinoma in situ; c. Other primary solid tumors treated curatively and no treatment administered \>= 2 years before enrollment, and in the investigator opinion, it is unlikely that there will be a recurrence =\< 1 year post enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, 5-FU, leucovorin, bevacizumab, and vitamin D3 and other agents used in study
• History of clinically significant bleeding within 6 months of enrollment
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this study
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery
• Known dihydropyrimidine dehydrogenase (DpD) deficiency
• History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)
• Serious, nonhealing wound, ulcer, or bone fracture
• Uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 95 mmHg despite medications)
• History of arterial thrombosis within the last 12 months
• History of visceral arterial ischemia
• Subjects unwilling or unable to comply with study requirements

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Leucovorin; Bevacizumab; Cholecalciferol; Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Limitations and Caveats

Due to the study's early termination and inadequate number of patients, no patients were analyzed.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Wen Wee Ma

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: September 8, 2010
• First Posted: September 10, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 21, 2014
• Results First Posted: July 21, 2014

Record last verified: 2014-06

Locations

US (1)