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

Primary Purpose

Uterine Cervical Neoplasms

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Zoledronic acid

About this trial

This is an interventional treatment trial for Uterine Cervical Neoplasms focused on measuring Uterine Cervical Cancer, Cancer of Cervix, Cervix Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Washington University

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Arm 1 (No Zometa)

Arm 2 (Zometa)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Incidence of Circulating Tumor Cells (CTCs)

Incidence of Disseminated Tumor Cells in Bone Marrow

Secondary Outcome Measures

Change in Bone Mineral Density

Change in Biochemical Markers of Bone Turnover

If Depressed and Anxious Moods Are Associated With Greater Impairment of Adaptive Immunity and Higher Levels of Angiogenesis in Peripheral Blood

Relationship of SUVmax and Metabolic Heterogeneity in the Primary Tumor and Evidence of Persistent/Recurrent Disease

Full Information

NCT ID

NCT00966992

First Posted

August 18, 2009

Last Updated

August 10, 2015

Sponsor

Washington University School of Medicine

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00966992

Brief Title

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

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Terminated

Why Stopped

Lack of enrollment

Study Start Date

August 2009 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uterine Cervical Neoplasms

Keywords

Uterine Cervical Cancer, Cancer of Cervix, Cervix Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 (No Zometa)

Arm Type

No Intervention

Arm Description

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.

Arm Title

Arm 2 (Zometa)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Zoledronic acid

Other Intervention Name(s)

Zometa

Primary Outcome Measure Information:

Title

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

Title

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

Secondary Outcome Measure Information:

Title

Change in Bone Mineral Density

Time Frame

At the time of diagnosis and 9 months after completion of treatment

Title

Change in Biochemical Markers of Bone Turnover

Time Frame

At the time of diagnosis and 9 months after completion of treatment

Title

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

Title

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

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Perry Grigsby, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University

City

St. Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.siteman.wustl.edu

Description

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

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

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