Bevacizumab Plus Gemcitabine, Docetaxel, Melphalan, and Carboplatin in Ovarian Cancer Patients

NCT ID: NCT00583622

Last Updated: 2013-05-21

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-31

Study Completion Date

2012-01-31

Brief Summary

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The goal of this clinical research study is to learn if bevacizumab, when given in combination with gemcitabine, docetaxel, melphalan and carboplatin, or with topotecan, cyclophosphamide and melphalan (if you are older than 60 or have an allergy to carboplatin), can help to control ovarian cancer during a stem cell transplant. The safety of this drug combination will also be studied.

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Detailed Description

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The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

Carboplatin is designed to damage the DNA (the genetic material) of cancer cells, which may cause them to die.

Melphalan is designed to damage the DNA of cells, which may cause cancer cells to die.

Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die.

Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may also help docetaxel, carboplatin, and melphalan to be more effective by stopping tumor cells from repairing damage caused by these drugs.

Topotecan is designed to damage the DNA of cells, which may cause cancer cells to die.

Cyclophosphamide is designed to damage the DNA of cells, which may cause cancer cells to die.

Stem Cell Removal:

Before you begin receiving the study drugs, you will have apheresis done to collect some of your stem cells as a part of your standard of care. Apheresis is the process of removing part of the blood (such as platelets or white blood cells) from the body in order to remove certain elements, such as stem cells. Then, the rest of the blood is returned back to your body.

Apheresis will be done through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain these procedures to you in more detail, and you will be required to sign a separate consent form for each procedure.

Your stem cells will be put back in your body after you finish receiving gemcitabine, docetaxel, melphalan, and carboplatin.

To prevent clotting, citrate (a blood thinner) will be added to the CVC during the apheresis procedure.

Study Drug Administration:

If you are found to be eligible to take part in this study, 2 weeks before your admission to the hospital (about 3 weeks before the stem cell transplant), you will receive bevacizumab through a the CVC over 45 minutes.

On Day 1 of your stay in the hospital, you will receive bevacizumab through the CVC over 45 minutes.

As part of standard mouth care, you will be asked to do mouthwashes 4 times a day (for 2 minutes each time) with caphosol (artificial saliva) followed by glutamine. Fifteen (15) minutes after each caphosol mouthwash, you will swish glutamine around in your mouth and gargle for 2 minutes, then spit it out. Do not swallow it.

On Day 2, through the CVC, you will receive gemcitabine over 3 hours and docetaxel over 2 hours. If you are allergic to carboplatin or older than 60 you will receive topotecan over 30 minutes.

On Day 3-5, through the CVC, you will receive gemcitabine over 3 hours, melphalan over 15 minutes, and carboplatin over 2 hours.

On Day 6, you will not receive any study drugs.

On Day 7, you will receive the stem cells through the CVC over about 30-60 minutes.

Starting the day after your stem cell transplant, as part of standard care, you will receive granulocyte-colony stimulating factor (G-CSF or filgrastim) as an injection under your skin daily, starting 1 day after the transplant, until your blood cell levels return to normal.

Starting 2 days after your transplant until 10 days after your transplant, you will receive methylprednisolone 2 times a day.

If you are allergic to carboplatin or older than 60:

On Day 1 of your stay in the hospital, you will receive bevacizumab through the CVC over 45 minutes.

On Day 2-4, through the CVC, you will receive cyclophosphamide over 2 hours and topotecan over 30 minutes. Each time you receive cyclophosphamide, you will also receive mesna to decrease the risk of bleeding in the bladder.

On Day 5-6, through the CVC, you will receive melphalan over 30 minutes and topotecan over 30 minutes.

On Day 7, you will not receive any study drugs.

On Day 8, you will receive the stem cells through the CVC over about 30-60 minutes.

Starting the day after your stem cell transplant, as part of standard care, you will receive G-CSF (filgrastim) as an injection under your skin daily, starting 1 day after the transplant, until your blood cell levels return to normal.

Study Visits:

At least once a week after the transplant, and then about 30, 60, and 100 days after your stem cell transplant, the following tests and procedures will be performed:

* Your medical history will be recorded.
* You will have a physical exam.
* You will be checked for possible reactions to the treatment, including graft-versus-host disease (GVHD) and graft failure. Graft failure occurs when donor cells may not be able to grow and multiply in your body. If this happens, there will be a high risk of infections and/or bleeding.
* Blood (about 3 tablespoons) will be drawn for routine tests and to check for tumor markers to check the status of the disease.
* Urine will be collected for routine tests.
* You will have a pelvic exam, if your doctor thinks it is needed.
* You will have an ECHO, if your doctor thinks it is needed.
* You will have a lung function test, if your doctor thinks it is needed.
* You will have CT scans of your chest, abdomen, and pelvis to check the status of the disease, if your doctor thinks it is needed.
* You will have a positron emission tomography - computed tomography (PET-CT) scan to check the status of the disease. A PET-CT is CT scan taken after a small amount of radioactive glucose (sugar) is injected into a vein to find cancer cells in the body.

These tests and procedures may be performed more often, if your doctor thinks it is needed.

End-of-Treatment Visit:

About 6 and 12 months after your stem cell transplant, then once a year after that (if your doctor thinks it is needed), the study visit tests and procedures listed above will be repeated.

Length of Study:

You will be off study after about 6 months. You will be taken off study early if the disease gets worse, if not enough stem cells can be collected, or if you experience any intolerable side effects.

Long-Term Follow-up:

If your doctor thinks it is necessary, you may have follow-up visits.

This is an investigational study. Bevacizumab is FDA approved and commercially available for the treatment of colorectal cancer. Gemcitabine, docetaxel, melphalan, and carboplatin are all FDA-approved and commercially available for the treatment of ovarian cancer. The use of bevacizumab with gemcitabine, docetaxel, melphalan, and carboplatin is investigational.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions

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Ovarian Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bevacizumab + High-Dose Chemotherapy

Bevacizumab 5 mg/kg by vein (IV) daily over 90 minutes for 2 Days + Carboplatin 333 mg/m\^2 by vein over 2 hours for 3 Days + Docetaxel 300 mg/m\^2 by vein over 2 hours for 1 Day + Gemcitabine 1,800 mg/m2 by vein over 3 hours for 4 Days + Melphalan 50 mg/m\^2 by vein over 15 minutes for 3 Days + Stem Cell Transplant

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type DRUG

5 mg/kg by vein daily over 90 minutes for 2 Days

Carboplatin

Intervention Type DRUG

333 mg/m\^2 by vein over 2 hours for 3 Days

Docetaxel

Intervention Type DRUG

300 mg/m\^2 by vein over 2 hours for 1 Day

Gemcitabine

Intervention Type DRUG

1,800 mg/m2 by vein over 3 hours for 4 Days

Melphalan

Intervention Type DRUG

50 mg/m\^2 by vein over 15 minutes for 3 Days

Stem Cell Transplant

Intervention Type PROCEDURE

* Stem Cell Removal via apheresis through a central venous catheter (CVC), usually in chest
* Stem Cell Replacement through CVC over about 30-60 minutes, Day 7 of treatment, following study drug regimen

Interventions

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Bevacizumab

5 mg/kg by vein daily over 90 minutes for 2 Days

Intervention Type DRUG

Carboplatin

333 mg/m\^2 by vein over 2 hours for 3 Days

Intervention Type DRUG

Docetaxel

300 mg/m\^2 by vein over 2 hours for 1 Day

Intervention Type DRUG

Gemcitabine

1,800 mg/m2 by vein over 3 hours for 4 Days

Intervention Type DRUG

Melphalan

50 mg/m\^2 by vein over 15 minutes for 3 Days

Intervention Type DRUG

Stem Cell Transplant

* Stem Cell Removal via apheresis through a central venous catheter (CVC), usually in chest
* Stem Cell Replacement through CVC over about 30-60 minutes, Day 7 of treatment, following study drug regimen

Intervention Type PROCEDURE

Other Intervention Names

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Avastin™ Anti-VEGF monoclonal antibody rhuMAb-VEGF Paraplatin® Taxotere Gemzar® Gemcitabine Hyrdrochloride SCT

Eligibility Criteria

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Inclusion Criteria

1. Age 18 - \<70.
2. Patients with advanced ovarian, fallopian or primary peritoneal cancer in second or later complete remission, or untreated or refractory relapse, defined as relapse within 6 months of prior platinum treatment or lack of response to salvage treatment.
3. No evidence of small bowel obstruction, as determined by CT scan of the abdomen and pelvis with oral and rectal contrast, within 30 days before the initiation of study treatment.
4. Adequate renal glomerular and tubular function, as defined by estimated serum creatinine clearance \>=60 ml/min, and urinary protein excretion \<=500 mg/day.
5. Adequate hepatic function, as defined by serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) \<=3 \* upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<=2 \* ULN or considered not clinically significant.
6. Adequate pulmonary function with Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) \>=50% of predicted, corrected for volume or hemoglobin.
7. Adequate cardiac function with left ventricular ejection fraction \>=45%. No uncontrolled arrhythmias or symptomatic cardiac disease.
8. Zubrod performance status \<2.

Exclusion Criteria

1. Failure to collect more than 3 \* 10e6 CD34+ stem cells/kg body weight
2. Patients with unresolved grade 3 or greater non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the principal investigator.
3. Major surgery within 30 days before the initiation of study treatment
4. Radiotherapy within 21 days prior to initiation of study treatment
5. Patients with active Central Nervous System (CNS) disease.
6. Evidence of acute or chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Principal Investigator and consider liver biopsy.
7. Uncontrolled infection, including HIV or HTLV-1 infection.
8. Aspirin (\> 325 mg/day) use within 10 days before initiation of study treatment.
9. Ongoing uncontrolled hypertension (\>140/90 mm Hg on medication).
10. Non-healing wound or significant traumatic injury within 30 days before the initiation of study treatment
11. Previous autologous or allogeneic stem cell transplant during the past year.
12. Positive Beta HCG test in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yago Nieto, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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U.T.M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center website

Other Identifiers

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2007-0368

Identifier Type: -

Identifier Source: org_study_id

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