Breast CancerPhase 2NCT00523809
Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor
A Phase 2 study testing Bevacizumab, Allogeneic Hematopoietic Stem Cell Transplantation and Fludarabine in people with Breast Cancer and Ovarian Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Breast Cancer, Ovarian Cancer
- What is being tested?
- Bevacizumab, Allogeneic Hematopoietic Stem Cell Transplantation and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Oct 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- From Age 18 to Age </= 65 years old.
- 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.
- Zubrod performance status </= 1.
- 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.
- 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.
- Adequate major organ functions.
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- Signed informed consent.
- 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.
- 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.
- Serum creatinine </= 2.0 mg/dL, or creatinine clearance > 40 mL/min.
- Serum bilirubin </= 1.5 mg/dL, and serum glutamic-pyruvic transaminase (SGPT) </= 3 * upper limit of normal.
Who cannot join
- Prior history of allogeneic stem cell transplantation.
- Life expectancy is severely limited by concomitant illness.
- Clinically significant active infections.
- HIV infection.
- Chronic active hepatitis.
- Pregnant or lactating women.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor
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.
Read the detailed 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.
- Conditions
- Breast Cancer, Ovarian Cancer
- Being tested
- Bevacizumab, Allogeneic Hematopoietic Stem Cell Transplantation, Fludarabine, Melphalan, Thymoglobulin
- Keywords
- Breast Cancer, Ovarian Cancer, Stem Cell Transplantation, Bevacizumab, Fludarabine, Melphalan, Avastin, Thymoglobulin, ATG, Antithymocyte Globulin, Allogeneic Hematopoietic Stem Cell Transplantation, AHSCT
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
10 mg/kg IV Daily Over 30 Minutes for 1 Day
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called NST
Stem Cell Transplantation on Day 8.
FludarabineDrug
Also called Fludarabine Phosphate
25 mg/m^2 IV Daily Over 30 Minutes for 5 Days
MelphalanDrug
70 mg/m^2 IV Daily Over 30 Minutes for 2 Days
ThymoglobulinDrug
Also called ATG, Antithymocyte Globulin
0.5 mg/kg IV on Day - 3, 1.5 mg/kg IV on Day - 2, and 2 mg/kg IV on Day -1.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Fludarabine + Melphalan | Experimental | Bevacizumab 10 mg/kg intravenous (IV) on Day 1; Fludarabine 25 mg/m^2 IV Daily over 5 Days; Melphalan 70 mg/m^2 IV Daily over 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; plus Allogeneic Hematopoietic Stem Cell Transplantation on Day 8. Receives: Drug: Bevacizumab; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Fludarabine; Drug: Melphalan; Drug: Thymoglobulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 100 days after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2007 (estimated)
- Study startAug 2007
- Primary completionOct 2011
- Study completionOct 2011
Why it stopped: Slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Naoto Ueno, MD, PhD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00523809
- Sponsor's protocol ID
- 2006-0873
- Status last verified
- Dec 2012
- First submitted
- 31 Aug 2007
- Last updated
- 28 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor
- ClinicalTrials.gov ID
- NCT00523809
- Acronym / sponsor ID
- 2006-0873
- Conditions
- Breast Cancer, Ovarian Cancer
- Keywords
- Breast Cancer, Ovarian Cancer, Stem Cell Transplantation, Bevacizumab, Fludarabine, Melphalan, Avastin, Thymoglobulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Aug 2007
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 3 Sep 2007 (estimated)
- Results
- Posted 28 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Fludarabine + Melphalan | Experimental | Drug: Bevacizumab, Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Drug: Fludarabine, Drug: Melphalan, Drug: ThymoglobulinBevacizumab 10 mg/kg intravenous (IV) on Day 1; Fludarabine 25 mg/m^2 IV Daily over 5 Days; Melphalan 70 mg/m^2 IV Daily over 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; plus Allogeneic Hematopoietic Stem Cell Transplantation on Day 8. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- From Age 18 to Age </= 65 years old.
- 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.
- Zubrod performance status </= 1.
- 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.
- 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.
Key exclusion criteria (7 listed)
- Prior history of allogeneic stem cell transplantation.
- Life expectancy is severely limited by concomitant illness.
- Clinically significant active infections.
- HIV infection.
- Chronic active hepatitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF10 mg/kg IV Daily Over 30 Minutes for 1 Day | Drug | Bevacizumab + Fludarabine + Melphalan |
| Allogeneic Hematopoietic Stem Cell TransplantationAlso: NSTStem Cell Transplantation on Day 8. | Procedure or surgery | Bevacizumab + Fludarabine + Melphalan |
| FludarabineAlso: Fludarabine Phosphate25 mg/m^2 IV Daily Over 30 Minutes for 5 Days | Drug | Bevacizumab + Fludarabine + Melphalan |
| Melphalan70 mg/m^2 IV Daily Over 30 Minutes for 2 Days | Drug | Bevacizumab + Fludarabine + Melphalan |
| ThymoglobulinAlso: ATG, Antithymocyte Globulin0.5 mg/kg IV on Day - 3, 1.5 mg/kg IV on Day - 2, and 2 mg/kg IV on Day -1. | Drug | Bevacizumab + Fludarabine + Melphalan |
Primary outcome
Progression-free Survival (PFS)
Time frame: 100 days after transplant
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naoto Ueno, MD, PhD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab, Allogeneic Hematopoietic Stem Cell Transplantation and Fludarabine in people with Breast Cancer and Ovarian Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: 100 days after transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2013.