Study of Zoledronic Acid Versus Observation on Bone Mineral Density and Incidence of Micrometastasis in Women Undergoing Pelvic Radiation for Cervical Cancer

Uterine Cervical Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00966992
• Other study ID #: 09-0811
• Status: Terminated
• Phase: Phase 2
• First received: August 18, 2009
• Last updated: August 10, 2015
• Start date: August 2009
• Est. completion date: March 2010

Study information

• Verified date: August 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

Intervention

Drug:
• Zoledronic acid

Locations

Country	Name	City	State
United States	Washington University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Circulating Tumor Cells (CTCs)		At time of diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment	No
Primary	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	No
Secondary	Change in Bone Mineral Density		At the time of diagnosis and 9 months after completion of treatment	No
Secondary	Change in Biochemical Markers of Bone Turnover		At the time of diagnosis and 9 months after completion of treatment	No
Secondary	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	No
Secondary	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	No

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine