Clinical trial NCT00966992: Study of Zoledronic Acid Versus Observation on Bone Mineral Density and Incidence of Micrometastasis in Women Undergoing Pelvic Radiation for Cervical Cancer
Official title: Randomized Phase II Study of Zoledronic Acid vs Observation on Bone Mineral Density and Incidence of Micrometastasis in Women Undergoing Pelvic Radiation for Cervical Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Keywords: Uterine Cervical Cancer
Cancer of Cervix
Cervix Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2009-08-27
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Circulating Tumor Cells (CTCs)
timeFrame: At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment
measure: Incidence of Disseminated Tumor Cells in Bone Marrow
timeFrame: At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment
Secondary outcomes:
measure: Change in Bone Mineral Density
timeFrame: At the time of diagnosis and 9 months after completion of treatment
measure: Change in Biochemical Markers of Bone Turnover
timeFrame: At the time of diagnosis and 9 months after completion of treatment
measure: If Depressed and Anxious Moods Are Associated With Greater Impairment of Adaptive Immunity and Higher Levels of Angiogenesis in Peripheral Blood
timeFrame: At diagnosis, 6 months after completion of treatment, and 9 months after completion of treatment
measure: Relationship of SUVmax and Metabolic Heterogeneity in the Primary Tumor and Evidence of Persistent/Recurrent Disease
timeFrame: 3 months after completion of treatment and 9 months after completion of treatment
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Perry Grigsby, M.D.
role: PRINCIPAL_INVESTIGATOR
References: