Clinical trial NCT01096381: Potential Biomarkers for Bevacizumab-Induced High Blood Pressure in Patients With Solid Tumor
Official title: A Prospective Clinical Trial Evaluating Potential Biomarkers for Bevacizumab Induced Hypertension
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Breast Cancer
Cardiovascular Complications
Colorectal Cancer
Fallopian Tube Cancer
Head and Neck Cancer
Lung Cancer
Ovarian Cancer
Peritoneal Cavity Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: cardiovascular complications
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
unspecified adult solid tumor, protocol specific
recurrent squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent adenoid cystic carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent verrucous carcinoma of the oral cavity
stage IV adenoid cystic carcinoma of the oral cavity
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV verrucous carcinoma of the oral cavity
recurrent basal cell carcinoma of the lip
recurrent squamous cell carcinoma of the lip and oral cavity
stage IV basal cell carcinoma of the lip
stage IV squamous cell carcinoma of the lip and oral cavity
metastatic squamous neck cancer with occult primary squamous cell carcinoma
recurrent metastatic squamous neck cancer with occult primary
untreated metastatic squamous neck cancer with occult primary
recurrent lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
fallopian tube cancer
peritoneal cavity cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-03-31
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with stage IV breast, colorectal, or non-small cell lung cancer (NSCLC) who will get bevacizumab as a standard of care, as well as patients with breast, colorectal, ovarian/fallopian tube/peritoneal, head and neck, or NSCLC cancer about to initiate bevacizumab. Where possible, the study population will include a control group not receiving bevacizumab.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Digital-pulse amplitude (DPA) measures
timeFrame: 1, 3 and 6 months after initiation of bevacizumab
Secondary outcomes:
measure: Relationship between hypertension and baseline DPA
timeFrame: 1, 3 and 6 months
measure: Endothelial progenitor cell levels pre- and post-bevacizumab
timeFrame: 1, 3 and 6 months
measure: Correlation between physical fitness level and cardiotoxicity
timeFrame: 1, 3 and 6 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Ingrid Mayer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt-Ingram Cancer Center
name: Ingrid Mayer, MD
role: PRINCIPAL_INVESTIGATOR
References: