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

NCT00920868 | Completed Phase 1 DMC

• 1 other identifier: Pro00010354
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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™ ).

Conditions

Solid Tumor; Metastatic Colorectal Cancer

Keywords

Phase I; Solid Tumor; Colorectal; Dasatinib; Sprycel; Bevacizumab; Avastin; Oxaliplatin; Eloxatin; Capecitabine; Xeloda; Duke; Any Solid Tumor (Phase I); Metastatic Colorectal Cancer (Expanded Cohort)

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose(MTD)/recommended phase II dose (RPTD) of capecitabine/oxaliplatin/bevacizumab/dasatinib for patients with advanced solid tumors.

  9 months

Secondary Outcomes (3)

• To further describe dose-limiting and non-dose-limiting toxicities associated with this regimen.

  12 months

• 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

  2 years

• To explore any correlation between blood, urine, and paraffin biomarkers and clinical outcomes

  3 years

Study Arms (1)

Dasatinib 50mg

EXPERIMENTAL

Cohort 1

Drug: dasatinib; Drug: bevacizumab; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

dasatinib DRUG

dasatinib at 50 mg PO BID)

Also known as: Sprycel

Dasatinib 50mg

bevacizumab DRUG

7.5 mg/kg IV day 1

Also known as: Avastin

Dasatinib 50mg

Oxaliplatin DRUG

130 mg/m2 IV day 1

Also known as: Eloxatin

Dasatinib 50mg

Capecitabine DRUG

850 mg/m2 PO BID on days 1-14

Also known as: Xeloda

Dasatinib 50mg

Eligibility Criteria

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

You may qualify if:

• Criteria Specific for Dose Escalation (Phase I)
• 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.
• 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
• Histologically documented adenocarcinoma of the colon or rectum that is metastatic/recurrent disease
• 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.
• 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
• Disease must be measurable by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
• Age \>18 years.
• Karnofsky performance status \> 70%.
• Life expectancy of at least 3 months.
• Patients must have adequate organ and marrow function as defined below:
• 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.
• All women of child bearing potential (WOCBP) MUST have a negative pregnancy test within 7 days prior to first receiving investigational product.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• 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).
• Patients who have received any other investigational agents within the 28 days prior to day 1 of study drug treatment.
• Patients with known central nervous system (CNS) metastases.
• Inadequately controlled hypertension
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• 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.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study drug treatment
• Core biopsy or other minor surgical procedure excluding placement of a vascular access device, within 7 days prior to expected start of treatment.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study day 1
• Serious, non-healing wound, ulcer, or bone fracture
• Proteinuria at screening
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study treatment day 1

Sponsors & Collaborators

• Herbert Hurwitz, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Duke Univeristy Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Strickler JH, McCall S, Nixon AB, Brady JC, Pang H, Rushing C, Cohn A, Starodub A, Arrowood C, Haley S, Meadows KL, Morse MA, Uronis HE, Blobe GC, Hsu SD, Zafar SY, Hurwitz HI. Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer. Invest New Drugs. 2014 Apr;32(2):330-9. doi: 10.1007/s10637-013-0042-9. Epub 2013 Nov 1.

  PMID: 24173967 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Dasatinib; Bevacizumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

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)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Herbert I Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 10, 2009
• First Posted: June 15, 2009
• Study Start: May 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: August 1, 2014
• Last Updated: February 3, 2016

Record last verified: 2016-02

Locations

US (2)