Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor

Breast Cancer Clinical Trial

Official title:

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00523809
• Other study ID #: 2006-0873
• Status: Terminated
• Phase: Phase 2
• First received: August 31, 2007
• Last updated: December 21, 2012
• Start date: August 2007
• Est. completion date: October 2011

Study information

• Verified date: December 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical research study is to learn if giving Avastin (bevacizumab) with standard chemotherapy and a blood stem cell transplant, in patients with an advanced solid tumor, can help to shrink the tumor or slow its growth. The safety of this treatment will also be studied.

Description:

The Study Drugs:

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

The combination of standard chemotherapy drugs (fludarabine and melphalan) used for this study may help to improve the chances of your body accepting the stem cell transplant. Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells) and weaken the immune system so that stem cells can stay in your body. Melphalan is designed to damage the cancer cells' DNA.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will have a central venous catheter inserted. A central venous catheter is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

You will receive chemotherapy with bevacizumab, fludarabine, and melphalan in order to prepare for the stem cell transplant.

On Day 1, you will receive bevacizumab through a needle in your vein over 30 minutes.

On Days 2-6, you will receive fludarabine by vein over 30 minutes.

On Day 5-6, you will receive melphalan by vein over 30 minutes.

On Day 7, you will receive no study drugs.

Stem Cell Transplant and Post-Transplant Drug Administration:

On Day 8, you will have a stem cell transplant. Your study doctor will explain this procedure to you in more detail and you will sign a separate consent form.

After the transplant, you will receive the drugs tacrolimus and methotrexate. Tacrolimus and methotrexate are used to prevent graft versus host disease (GVHD), a condition that occurs when the transplanted cells attack the normal cells in the body.

Tacrolimus will be given by vein non-stop (24 hours a day) until you are able to take medications by mouth. Once you are able to take medications by mouth, your doctor will tell you how and when to take the oral medication. You will receive tacrolimus for 2-3 months. During the last month that tacrolimus is given, the dose will be lowered gradually.

Methotrexate will be given by vein over a few seconds on Days 9, 11, and 14. An additional dose of methotrexate will be given on Day 19 if your donor is your parent, child, or an unrelated family member.

If GVHD does occur, the GVHD will be treated with methylprednisolone by vein or by mouth, as needed. You may also be given steroid cream to use on the skin, if needed.

Starting at least 3 weeks after the transplant, as soon as your blood counts recover, you will receive bevacizumab every 2 weeks by vein over 30 minutes.

Post-Transplant Procedures:

You must stay in the hospital for about 3-4 weeks beginning on Day 1. While you are in the hospital, blood (about 2 teaspoons) will be drawn for routine tests every day.

You must stay in the Houston area for about 100 days after the transplant. Once a month during the 100 days after the transplant, and then every 3 months for the first year, you will have scans to check the status of the disease. The study doctor will decide which scans are necessary (chest x-rays, CT scans, and/or bone scans). You may also have a bone marrow aspirate and biopsy at these times. The bone marrow aspirate and biopsy would only be performed if your bone marrow was shown to be involved with the disease at the time of screening.

If the disease is still present at 2 months after the transplant, and you do not have GVHD, you will stop receiving tacrolimus within 2 weeks. After that, if the disease is still present after another 6 weeks, and you do not have GVHD, you may receive an infusion of donor lymphocytes (a type of white blood cell) by vein over about 30 minutes. This treatment with white blood cells may be repeated 2 more times with 6 weeks between each infusion.

Length of Study:

You will be taken off-study after 1 year.

Follow-Up Visits:

You will have follow-up visits as per standard of care.

This is an investigational study. The use of bevacizumab in transplant patients is not FDA approved. Melphalan and fludarabine are FDA approved and commercially available for transplant patients. Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. From Age 18 to Age </= 65 years old.

2. Patients must have one of the following diseases. 1) metastatic breast cancer which achieved a tumor response (complete response (CR) or partial response (PR)) by pre-transplant therapy. For bone only metastatic breast cancer, a tumor response of stable disease (SD) is accepted. 2) low grade advanced ovarian cancer 3) high grade advanced ovarian cancer which achieved antitumor response (CR or PR) by pre-transplant therapy.

3. Zubrod performance status </= 1.

4. An HLA-matched (6/6 matches) related donor or unrelated donor (8/8 matches) willing and able to donate peripheral blood stem cell (PBSC) or bone marrow and/or lymphocytes by conventional techniques.

5. Requirement of prior treatment. For metastatic renal cell carcinoma (RCC) two prior treatments, which include targeted therapy (e.g. Sorafenib and Stutent). For breast and ovarian cancer, one prior treatment which include chemotherapy.

6. Adequate major organ functions.

7. Signed informed consent.

8. Left ventricular ejection fraction >/= 45%. Cardiology clearance is needed if the patient has left ventricular ejection fraction of < 45%, uncontrolled arrhythmias, or symptomatic cardiac disease.

9. Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) >/= 50% of predicted value. Pulmonary clearance is needed if the patient has FEV1, FVC, or DLCO < 50% of predicted valued or any symptomatic pulmonary disease.

10. Serum creatinine </= 2.0 mg/dL, or creatinine clearance > 40 mL/min.

11. Serum bilirubin </= 1.5 mg/dL, and serum glutamic-pyruvic transaminase (SGPT) </= 3 * upper limit of normal.

Exclusion Criteria:

1. Prior history of allogeneic stem cell transplantation.

2. Life expectancy is severely limited by concomitant illness.

3. Clinically significant active infections.

4. HIV infection.

5. Chronic active hepatitis.

6. Pregnant or lactating women.

7. Presence of, or prior history of multiple brain metastasis. If patient has prior single brain metastasis treated with complete surgical resection or stereotactic radiation therapy, radiological imaging has to demonstrate no recurrence or no brain edema for at least 6 months from the end of the treatment.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Bevacizumab
10 mg/kg IV Daily Over 30 Minutes for 1 Day

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Stem Cell Transplantation on Day 8.

Drug:
• Fludarabine
25 mg/m^2 IV Daily Over 30 Minutes for 5 Days
• Melphalan
70 mg/m^2 IV Daily Over 30 Minutes for 2 Days
• Thymoglobulin
0.5 mg/kg IV on Day - 3, 1.5 mg/kg IV on Day - 2, and 2 mg/kg IV on Day -1.

Locations

Country	Name	City	State
United States	U.T.M.D. Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Number or participants with no disease progression or death for any reason during first 100 days following transplantation. Participants followed every 3 months for first year.	100 days after transplant	No

External Links

•   MD Anderson Cancer Center