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

NCT ID: NCT00920868

Last Updated: 2016-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2014-08-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dasatinib 50mg

Cohort 1

Group Type: EXPERIMENTAL

dasatinib

Intervention Type: DRUG

dasatinib at 50 mg PO BID)

bevacizumab

Intervention Type: DRUG

7.5 mg/kg IV day 1

Oxaliplatin

Intervention Type: DRUG

130 mg/m2 IV day 1

Capecitabine

Intervention Type: DRUG

850 mg/m2 PO BID on days 1-14

Interventions

dasatinib

dasatinib at 50 mg PO BID)

Intervention Type: DRUG

bevacizumab

7.5 mg/kg IV day 1

Intervention Type: DRUG

Oxaliplatin

130 mg/m2 IV day 1

Intervention Type: DRUG

Capecitabine

850 mg/m2 PO BID on days 1-14

Intervention Type: DRUG

Other Intervention Names

Sprycel; Avastin; Eloxatin; Xeloda

Eligibility 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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Herbert Hurwitz, MD

OTHER

Sponsor Role: lead

Responsible Party

Herbert Hurwitz, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Herbert I Hurwitz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Rocky Mountain Cancer Center

Denver, Colorado, United States

Duke Univeristy Medical Center

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24173967 (View on PubMed)

Other Identifiers

Pro00010354

Identifier Type: -

Identifier Source: org_study_id