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

This study has been terminated.
(Lack of enrollment)
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00966992
First received: August 18, 2009
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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 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.


Condition Intervention Phase
Uterine Cervical Neoplasms
Drug: Zoledronic acid
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Bone mineral density [ Time Frame: At diagnosis and 9 months after completion of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of disseminated tumor cells in bone marrow and circulating tumor cells [ Time Frame: At diagnosis, 3 months after completion of treatment, and 9 months after completion of treatment ] [ Designated as safety issue: No ]
  • Change in biochemical markers of bone turnover [ Time Frame: At time of diagnosis and 9 months after completion of treatment ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: August 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 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.
Experimental: 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 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 DEXA and biomarker studies.
Drug: Zoledronic acid
Other Name: Zometa

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 SUVMax and metabolic heterogeneity in the primary tumor and evidence of persistent/recurrent disease on the 3 and 9 month FDG-PET scans with DTCs and CTCs.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven squamous, adenosquamous or adenocarcinoma 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00966992

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Novartis Pharmaceuticals
Investigators
Principal Investigator: Perry Grigsby, M.D., M.S., M.B.A Washington University Early Recognition Center
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00966992     History of Changes
Other Study ID Numbers: 09-0811
Study First Received: August 18, 2009
Last Updated: July 9, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Uterine Cervical Cancer
Cancer of Cervix
Cervix Cancer

Additional relevant MeSH terms:
Neoplasms
Uterine Cervical Neoplasms
Neoplasm Micrometastasis
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014