Potential Biomarkers for Bevacizumab-Induced High Blood Pressure in Patients With Solid Tumor

Breast Cancer Clinical Trial

Official title:

A Prospective Clinical Trial Evaluating Potential Biomarkers for Bevacizumab Induced Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01096381
• Other study ID #: VICC BRE 0983
• Secondary ID: P30CA068485VU-VI
• Status: Terminated
• Phase: N/A
• First received: March 30, 2010
• Last updated: February 23, 2012
• Start date: March 2010
• Est. completion date: August 2011

Study information

• Verified date: February 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Vanderbilt University Human Research Protection Program
• Study type: Observational

Clinical Trial Summary

RATIONALE: Studying samples of blood and urine in the laboratory from patients with cancer receiving bevacizumab may help doctors learn more about changes that occur in DNA and identify biomarkers related to high blood pressure.

PURPOSE: This phase I trial is studying potential biomarkers for bevacizumab-induced high blood pressure in patients with malignant solid tumors, including breast cancer, colorectal cancer, non-small cell lung cancer, head and neck cancer, ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma.

Description:

OBJECTIVES:

Primary

• To measure the endothelial function over time, including non-invasive assessment of digital-pulse amplitude via Endo-pat test, serum tPA, PAI-1, VEGF, urine TXa2, and PGI-M, in patients with solid malignancies treated with chemotherapy with or without bevacizumab.

• To compare endothelial function changes between patients who develop hypertension (HTN) versus patients who do not develop HTN.

Secondary

• To compare circulating soluble cytokines, proangiogenic factors, glucose tolerance, and cardiac biomarkers over time in these patients.

• To compare endothelial progenitor cell levels pre- and post-bevacizumab in these patients.

• To assess whether physical fitness level at baseline and at 3 months after treatment initiation (assessed subjectively by questionnaire) correlates with relative risk of developing NCI grade ≥ I cardiotoxicity.

OUTLINE: Patients undergo 24-hour blood pressure monitoring at baseline, before second bevacizumab therapy, and periodically during study. Patients also undergo a digital-pulse amplitude measurement periodically during study.

Blood samples are collected at baseline and periodically during study for circulating soluble cytokines, proangiogenic factors, glucose tolerance, cardiac biomarkers, and endothelial progenitor cell level studies. Patients also undergo 24-hour urine sample collection at baseline and periodically during study for protein, creatinine, and metabolites of prostacyclin and thromboxane.

Patients complete physical activity questionnaires at baseline and at 3 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: August 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients with stage IV or unresectable recurrent cancer (except for renal cell carcinoma and glioblastoma multiforme) that will get bevacizumab as a standard of care, as well as patients about to initiate bevacizumab within the protocols:

• ECOG5103: A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide followed by Paclitaxel with Bevacizumab or Placebo in Patients with Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer.

• ECOG1505: A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (> 4 cm) - IIIA Non-Small Cell Lung Cancer (NSCLC)

• ECOG5202: A Randomized Phase III Study Comparing 5-FU, Leucovorin and Oxaliplatin versus 5-FU, Leucovorin, Oxaliplatin and Bevacizumab in Patients with Stage II Colon Cancer at High Risk for Recurrence to Determine Prospectively the Prognostic Value of Molecular Markers

• ECOG1305: Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients with Recurrent or Metastatic Head and Neck Cancer

• GOG0252: A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma

• GOG0086P: A Three Arm Randomized Phase II Study of Paclitaxel/Carboplatin/Bevacizumab, Paclitaxel/Carboplatin/Temsirolimus, and Ixabepilone/Carboplatin/Bevacizumab as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer (Only those arms including bevacizumab)

• GOG0250: A Randomized Phase III Evaluation of Docetaxel and Gemcitabine Plus G-CSF with Bevacizumab Versus Docetaxel and Gemcitabine Plus G-CSF with Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus

• GOG0240: A Randomized Phase III Evaluation of Docetaxel and Gemcitabine Plus G-CSF with Bevacizumab Versus Docetaxel and Gemcitabine Plus G-CSF with Placebo in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus

• THO0640: A Phase II Multi Center Study Investigating Translational Science in Chemotherapy-Naïve Patients with Stage IIIB or IV Non-Small Cell Lung Cancer (NSCLC) treated with the EGFR-TKI, Erlotinib (SPECS)

Eligibility Criteria:

• Patients = 18 years of age with stage IV or unresectable recurrent cancer (except for renal cell carcinoma and glioblastoma multiforme) that will get bevacizumab as a standard of care.

• Patients = 18 years of age with histologically confirmed breast, colorectal or non-small cell lung (NSCL) cancer that have completed surgical treatment for stages I
• III cancer and are going to initiate adjuvant therapy within one of the 3 clinical trials addressing the role of bevacizumab added to chemotherapy in the adjuvant setting of breast, colorectal and NSCL cancer (E5103, E1505 and E5202)

• Patients = 18 years of age with histologically confirmed squamous cell carcinoma of the head and neck (recurrent or metastatic) who are about to initiate chemotherapy with or without bevacizumab within E1305 clinical trial.

• Patients = 18 years of age who are about to initiate chemotherapy with bevacizumab within the following trials: GOG0252, GOG0086P (only those patients receiving bevacizumab arms), GOG0250, and GOG0240.

• Patients = 18 years of age with a histologic diagnosis of non small cell lung cancer who are about to initiate bevacizumab within THO0640 clinical trial.

• Patients must provide informed written consent.

Ineligibility Criteria

• Patients with active renal cell carcinoma or glioblastoma multiforme

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Cardiovascular Complications
• Colorectal Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Cancer
• Ovarian Cancer
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Other:
• laboratory biomarker analysis
Blood collection
• questionnaire administration
Survey regarding baseline health and activity level.

Locations

Country	Name	City	State
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Digital-pulse amplitude (DPA) measures		1, 3 and 6 months after initiation of bevacizumab	No
Secondary	Relationship between hypertension and baseline DPA		1, 3 and 6 months	No
Secondary	Endothelial progenitor cell levels pre- and post-bevacizumab		1, 3 and 6 months	No
Secondary	Correlation between physical fitness level and cardiotoxicity		1, 3 and 6 months	No