Uterine Cervical Neoplasms
Conditions
Keywords
Uterine Cervical Cancer, Cancer of Cervix, Cervix Cancer
Brief summary
The treatment of cervical cancer with chemotherapy and radiation will make women post menopausal (no estrogen from the ovaries), if a woman is not already in menopause. Estrogen plays a key role in maintaining bone health. Therefore, these women are at higher risk of getting osteoporosis (decrease minerals in the bone) and bone fractures. The overall purpose of this research is to look at the effects of zoledronic acid (Zometa) on preventing bone loss. Studies have also shown that zoledronic acid may prevent metastasis to the bone which can occur in women with cervical cancer. Zometa is investigational (not approved by the Food and Drug Administration (FDA)) in this study to prevent metastasis to the bone in women with cervical cancer. Therefore, the goal of this study is to also look at the effects of zoledronic acid (Zometa) on circulating tumor cells in the bone marrow and blood. This study is being done to find a way to prevent bone loss and metastasis to the bone in women undergoing chemotherapy and radiation for cervical cancer. An additional component of the study is to assess the importance of stress on immune markers in blood during standard treatment.
Detailed description
OBJECTIVES * To determine the incidence of disseminated tumor cells (DTCs) in bone marrow and circulating tumor cells (CTCs) in the blood of women with cervical cancer at diagnosis and 3 to 9 months after chemotherapy and pelvic radiation with and without Zometa. * To determine the change in biochemical markers of bone turnover from diagnosis to 9 months after radiation in women receiving chemoradiation for cervical cancer with and without Zometa. * To determine change in bone mineral density from diagnosis to 9 month after chemoradiation with and without Zometa. * To determine if depressed and anxious mood are associated with greater impairment of adaptive immunity (ratio of Th1/Th2) and higher levels of angiogenesis (VEGF) in peripheral blood of cervical cancer patients. * To examine the relationship of standardized uptake values (SUV)Max and metabolic heterogeneity in the primary tumor and evidence of persistent/recurrent disease on the 3 and 9 month Fludeoxyglucose (FDG)-Positron Emission Tomography (PET) scans with DTCs and CTCs.
Interventions
DRUGZoledronic acid
Sponsors
Novartis Pharmaceuticals
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven squamous, adenosquamous or adenocarcinoma International Federation of Gynecology and Obstetrics (FIGO) Stage IB-IVA of the uterine cervix undergoing initial radiation and cisplatin based chemotherapy for primary treatment. * Gynecologic Oncology Group performance status of 0, 1, or 2. * Patients with ureteral obstruction must undergo stent placement or nephrostomy tube placement prior to study entry. * Age \>= 18 years. * Patients must have signed informed consent. * Patients must have adequate: * Bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTCAE) grade 1. Platelets greater than or equal to 100,000/ul. * Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN). If creatinine is greater than 1.5 x ULN, creatinine clearance must be greater than 60 ml/min. * Hepatic function: bilirubin less than or equal to 1.5 x ULN. AST and alkaline phosphatase less than or equal to 2.5 x ULN. * Neurologic function: neuropathy (sensory and motor) less than or equal to CTCAE grade 1. * Coagulation: prothrombin time (PT) such that the international normalized ratio (INR) is \< 1.5 (INR may be between 2 and 3 if a patient is on stable dose of therapeutic warfarin) and a PTT \< 1.2 times control.
Exclusion criteria
* Evidence of sepsis or severe infection. * Previous or current treatment for osteoporosis. Patients with denovo osteoporosis are also excluded. * Evidence of bone metastasis. * Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), or exposed bone in the mouth, or of slow healing after dental procedures. * Recent (within 6 weeks) or planned dental or jaw surgery (e.g., extraction, implants). * Patients with history of other invasive malignancy (treatment within the last 5 years) other than non-melanoma skin cancer. * Patients with known hypersensitivity to Zometa or other bisphosphonates. * Patients who are pregnant or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Circulating Tumor Cells (CTCs) | At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment |
| Incidence of Disseminated Tumor Cells in Bone Marrow | At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Change in Bone Mineral Density | At the time of diagnosis and 9 months after completion of treatment |
| Change in Biochemical Markers of Bone Turnover | At the time of diagnosis and 9 months after completion of treatment |
| If Depressed and Anxious Moods Are Associated With Greater Impairment of Adaptive Immunity and Higher Levels of Angiogenesis in Peripheral Blood | At diagnosis, 6 months after completion of treatment, and 9 months after completion of treatment |
| Relationship of SUVmax and Metabolic Heterogeneity in the Primary Tumor and Evidence of Persistent/Recurrent Disease | 3 months after completion of treatment and 9 months after completion of treatment |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on 08/12/2009 and closed to participant enrollment on 08/31/2010.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 (No Zometa) Women will complete their standard chemoradiation treatment protocol and end of treatment PET scan at about 3 months from completion of radiation. All interventions on this arm are standard of care. | 3 |
| Arm 2 (Zometa) Women will complete their standard chemoradiation treatment protocol and end of treatment PET scan at about 3 months from completion of radiation. Women randomized to zoledronic acid will receive 4 mg intravenously (IV) with their first dose chemotherapy and 3, 6 and 9 months after completion of radiation (total of 4 doses) along with scheduled follow-up dual-energy X-ray absorptiometry (DEXA) and biomarker studies.
Zoledronic acid | 0 |
| Total | 3 |
Baseline characteristics
| Characteristic | Arm 1 (No Zometa) | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 participants | 0 participants |
| Age, Categorical >=65 years | 1 participants | 1 participants |
| Age, Categorical Between 18 and 65 years | 2 participants | 2 participants |
| Gender Female | 3 participants | 3 participants |
| Gender Male | 0 participants | 0 participants |
| Region of Enrollment United States | 3 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 0 / 0 |
| serious Total, serious adverse events | 0 / 3 | 0 / 0 |
Outcome results
Primary
Incidence of Circulating Tumor Cells (CTCs)
Time frame: At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.
Primary
Incidence of Disseminated Tumor Cells in Bone Marrow
Time frame: At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.
Secondary
Change in Biochemical Markers of Bone Turnover
Time frame: At the time of diagnosis and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.
Secondary
Change in Bone Mineral Density
Time frame: At the time of diagnosis and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.
Secondary
If Depressed and Anxious Moods Are Associated With Greater Impairment of Adaptive Immunity and Higher Levels of Angiogenesis in Peripheral Blood
Time frame: At diagnosis, 6 months after completion of treatment, and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.
Secondary
Relationship of SUVmax and Metabolic Heterogeneity in the Primary Tumor and Evidence of Persistent/Recurrent Disease
Time frame: 3 months after completion of treatment and 9 months after completion of treatment
Population: This outcome measure could not be analyzed as there were no participants enrolled in the zometa arm and the outcome measure required comparing results from the no zometa arm to the zometa arm.