XAD - Xelox (Capecitabine + Oxaliplatin) + Bevacizumab + Dasatinib

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Herbert Hurwitz, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00920868
First received: June 10, 2009
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

The primary purpose of this study is to find the highest tolerated dose of the study drugs: capecitabine, oxaliplatin, bevacizumab, and dasatinib given in combination to subjects with advanced solid tumors. This will occur in the first part of the study (Phase I). Once this dose has been determined, it will be given to subjects with advanced metastatic colorectal cancer in the second part of the study (Phase II).

By giving these drugs in combination, researchers hope to evaluate the side effects of the study drugs in both groups, and to determine if this combination could possibly decrease or stabilize the cancer being treated.

Subjects will be enrolled at Duke University Medical Center (DUMC) and Rocky Mountain Cancer Center.

After satisfying eligibility and screening criteria, patients will be treated on 21 day cycles.

ABOUT THE STUDY DRUGS

  • Capecitabine (Xeloda™) is an oral (taken by mouth) chemotherapy drug in tablet form made by Roche Laboratories Inc. Capecitabine has been approved for use by the Food and Drug Administration (FDA) for first line treatment (treatment that should be used for cancer that has not been treated yet) of metastatic colorectal cancer and also for metastatic breast cancer.
  • Oxaliplatin (Eloxatin™) is an intravenous (given by injection into a vein) chemotherapy drug made by Sanofi-Synthélabo. This drug is also approved by the FDA for use in metastatic colorectal cancer.
  • Bevacizumab (Avastin™) is a type of intravenous cancer treatment called anti-angiogenic therapy (a type of therapy to treat cancer that interferes with blood flow to the tumor, thereby stopping tumor growth, and possibly leading to tumor shrinkage) made by Genentech Inc. Bevacizumab is approved by the FDA for first line treatment of metastatic colorectal cancer in combination with other chemotherapy.
  • Dasatinib (Sprycel™) is an oral drug made by Bristol Myers Squib, Inc (BMS). Dasatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML), acute lymphoblastic leukemia or for patients that are resistant to a medicine called imatinib mesylate (Gleevec™ ).

Condition Intervention Phase
Solid Tumor
Metastatic Colorectal Cancer
Drug: dasatinib
Drug: bevacizumab
Drug: Oxaliplatin
Drug: Capecitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Capecitabine, Oxaliplatin, Bevacizumab, and Dasatinib for Patients With Advanced Solid Tumors With Expanded Cohort of Patients With Previously Untreated Metastatic Colorectal Cancer.

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To determine the maximum tolerated dose(MTD)/recommended phase II dose (RPTD) of capecitabine/oxaliplatin/bevacizumab/dasatinib for patients with advanced solid tumors. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To further describe dose-limiting and non-dose-limiting toxicities associated with this regimen. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To describe clinical activity (partial response (PR), complete response (CR) or stable disease (SD)>6 months, time to progression, and overall survival) associated with this regimen for patients with previously untreated metastatic and/or re [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To explore any correlation between blood, urine, and paraffin biomarkers and clinical outcomes [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: May 2009
Study Completion Date: August 2014
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib 50mg
Cohort 1
Drug: dasatinib
dasatinib at 50 mg PO BID)
Other Name: Sprycel
Drug: bevacizumab
7.5 mg/kg IV day 1
Other Name: Avastin
Drug: Oxaliplatin
130 mg/m2 IV day 1
Other Name: Eloxatin
Drug: Capecitabine
850 mg/m2 PO BID on days 1-14
Other Name: Xeloda

  Eligibility

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

Inclusion Criteria:

Criteria Specific for Dose Escalation (Phase I)

  1. Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom capecitabine, oxaliplatin, and/or bevacizumab would be considered a standard therapy or therapeutic option.
  2. Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1.

Criteria Specific for Expanded Cohort Portion of Trial Only

  1. Histologically documented adenocarcinoma of the colon or rectum that is metastatic/recurrent disease
  2. No prior chemotherapy for metastatic/recurrent colorectal cancer. Patients may have received a radiosensitizing dose of 5-fluorouracil or capecitabine for the treatment of local disease in the localized or metastatic setting.
  3. No history of other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer
  4. Disease must be measurable by Response Evaluation Criteria In Solid Tumors (RECIST) criteria

Inclusion Criteria for All Participants

  1. Age >18 years.
  2. Karnofsky performance status > 70%.
  3. Life expectancy of at least 3 months.
  4. Patients must have adequate organ and marrow function as defined below:
  5. Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
  6. All women of child bearing potential (WOCBP) MUST have a negative pregnancy test within 7 days prior to first receiving investigational product.
  7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria for ALL Subjects:

  1. Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within the 28 days prior to day 1 of the study (ie - first day of study drug treatment).
  2. Patients who have received any other investigational agents within the 28 days prior to day 1 of study drug treatment.
  3. Patients with known central nervous system (CNS) metastases.
  4. Inadequately controlled hypertension
  5. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
  6. Symptomatic peripheral vascular disease
  7. Evidence of bleeding diathesis or coagulopathy. Patients on full-dose anticoagulation are permitted to enroll provided that they have been clinically stable on anti- coagulation.
  8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study drug treatment
  9. Core biopsy or other minor surgical procedure excluding placement of a vascular access device, within 7 days prior to expected start of treatment.
  10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study day 1
  11. Serious, non-healing wound, ulcer, or bone fracture
  12. Proteinuria at screening
  13. Any prior history of hypertensive crisis or hypertensive encephalopathy
  14. New York Heart Association (NYHA) Grade II or greater congestive heart failure
  15. History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study treatment day 1
  16. History of stroke or transient ischemic attack within 6 months prior to study treatment day 1
  17. History of intolerance or hypersensitivity to prior treatment with capecitabine, oxaliplatin, bevacizumab and/or dasatinib.
  18. No previous treatment with dasatinib.
  19. Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil, or known dihydropyrimidine dehydrogenase (DPD) deficiency.
  20. Patient with grade 2 or greater peripheral neuropathy
  21. Chronic treatment with systemic steroids or another immunosuppressive agent.
  22. Other concurrent severe and/or poorly controlled medical condition that could compromise safety of treatment as so judged by treating physician.
  23. A known history of HIV seropositivity,hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
  24. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection)
  25. Patients unwilling to or unable to comply with the protocol
  26. Diagnosed or congenital long QT syndrome
  27. Any history of clinically significant ventricular arrhythmias
  28. Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)
  29. Pleural effusion grade > 2.
  30. Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
  31. History of significant bleeding disorder unrelated to cancer
  32. Patients actively taking proton pump inhibitors or H2 antagonists will be excluded from this study.
  33. Any psychiatric illness/social situations that would limit safety or compliance with study requirements
  34. Medications that inhibit platelet function (except low dose aspirin as defined in study protocol)
  35. Use of medications that are either Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
  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: NCT00920868

Locations
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, North Carolina
Duke Univeristy Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Herbert Hurwitz, MD
Bristol-Myers Squibb
Investigators
Principal Investigator: Herbert I Hurwitz, MD Duke University
  More Information

No publications provided

Responsible Party: Herbert Hurwitz, MD, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00920868     History of Changes
Other Study ID Numbers: Pro00010354
Study First Received: June 10, 2009
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
Phase I
Solid Tumor
Colorectal
Dasatinib
Sprycel
Bevacizumab
Avastin
Oxaliplatin
Eloxatin
Capecitabine
Xeloda
Duke
Any Solid Tumor (Phase I)
Metastatic Colorectal Cancer (Expanded Cohort)

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Dasatinib
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014