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Estrogen Receptor-negative Breast CancerPhase 2NCT00003199

Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

A Phase 2 study testing tamoxifen citrate, busulfan and thiotepa in people with Estrogen Receptor-negative Breast Cancer and Estrogen Receptor-positive Breast Cancer, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well giving combination chemotherapy and peripheral blood stem cell transplant followed by aldesleukin and sargramostim works in treating patients with inflammatory stage IIIB or metastatic stage IV breast cancer. Read more about this study

Who is it for?
Ages 19 to 65 years
What is being tested?
tamoxifen citrate, busulfan and thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Nov 1997to Dec 2009
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 19 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with metastasis to soft tissue and/or bone; responsive stage IV disease is defined as patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR following initial chemotherapy for metastatic disease or patients with locally recurrent disease (chest wall/axillary nodes) who are rendered disease-free following surgery or radiation therapy without receiving chemotherapy; bone disease is categorized as responsive if there is demonstrated sclerosis of prior lesions with no new lesions
  • Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes) patients rendered NED by RT or surgery do not need to receive chemotherapy for stage IV disease prior to Cytoxan/Taxol
  • Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol 506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and before transplant
  • Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were collected by using G-CSF according to FHCRC protocol 753; patient has an adequate number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg)
  • The patient must have the capacity to give informed consent; the patient must have signed an approved consent form conforming with federal and institutional guidelines
  • Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal
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  • Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min
  • Pre-Study tests have been performed as outlined in the Study Calendar
  • Patients will begin IL-2/GM-CSF therapy if they meet the following criteria post-transplant:
  • Can start therapy 30 to 100 days after transplant
  • Karnofsky performance status > 60
  • ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent) for at least 5 days before starting therapy
  • Total bilirubin =< 2.5 x upper limit of normal
  • SGOT =< 2.5 x upper limit of normal
  • Creatinine =< 2.0 mg/dl

Who cannot join

  • Patients with a Karnofsky Performance Score less than 70
  • Patients with a left ventricular ejection fraction less than 50 % (LVEF must be performed in patients with symptoms of CHF, abnormal cardiac exam or history of Adriamycin therapy total dose > 400 mg/m^2)
  • Patient is pregnant
  • Patient is seropositive for the human immunodeficiency virus
  • Patients with a history of seizures
  • Patients with hypersensitivity to E.coli preparations
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  • Patients with active auto-immune disease
  • Patients with clinically significant pulmonary disease, i.e., diffusion capacity corrected < 60% of predicted; patients with pulmonary problems should be evaluated with appropriate pulmonary studies and/or consult
  • Patients with a history of CNS lesion (brain or carcinoid meningitis)
  • Patients with significant active infection precluding transplant
  • Patients who have had more than one prior chemotherapy regimen for stage IV disease or a prior transplant for any stage disease
  • Patients who have had CD34+ selection of their PBSC products
  • Patients will not receive IL-2/GM-CSF therapy if they:
  • Are > 100 days from transplant
  • Have documented disease progression after transplant
  • Have an active infection
  • Manifested cardiac complications during the initial transplant period, including arrhythmias (that required therapy), congestive heart failure, angina, myocardial infarct, or decreased LVEF to < 45%
  • Currently have pericardial effusions, pleural effusions or ascites
  • Manifested pulmonary toxicity during the initial transplant period and have a diffusion capacity corrected =< 60%
  • Are on steroids
  • Currently have a Grade 3 toxicity from BuMelTT
  • If the patient does not wish to receive the therapy

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Fred Hutchinson Cancer Research Center/Puget Sound Oncology Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Trial for Patients With Inflammatory (Stage IIIB) and Responsive Metastatic Stage IV Breast Cancer Using Busulfan, Melphalan and Thiotepa Followed by Autologous or Syngeneic PBSC Rescue and 12 Weeks of Post-Engraftment Immunotherapy With Low-Dose IL-2 and GM-CSF

This phase II trial studies how well giving combination chemotherapy and peripheral blood stem cell transplant followed by aldesleukin and sargramostim works in treating patients with inflammatory stage IIIB or metastatic stage IV breast cancer. Drugs used in chemotherapy, such as busulfan, melphalan, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed. Aldesleukin may stimulate the white blood cells to kill breast cancer cells. Giving aldesleukin together with sargramostim may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the event-free survival and survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.

SECONDARY OBJECTIVES:

II. To determine the toxicity of a combination of low-dose IL-2 and GM-CSF in patients following HDC with BUMELTT and PBSC support.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive busulfan orally (PO) once every 6 hours on days -8, -7, and -6; melphalan IV over 30 minutes on days -5 and -4; and thiotepa IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell infusion on day 0.

POST-TRANSPLANT THERAPY: All patients receive tamoxifen citrate* PO once daily beginning prior to aldesleukin (IL-2) and sargramostim (GM-CSF) therapy and continuing for 5 years or until relapse (estrogen receptor [ER]- or progesterone receptor [PR]-positive patients) OR until completion of IL-2/GM-CSF therapy (ER-negative or PR-negative patients). Eligible patients receive IL-2 subcutaneously (SC) daily and GM-CSF SC 3 times weekly for 12 weeks beginning 30-100 days after transplantation. Patients may receive radiotherapy after completion of IL-2/GM-CSF treatment if no prior radiotherapy was given before transplantation.

*Stage IV patients not receiving IL-2/GM-CSF therapy who received tamoxifen citrate as part of adjuvant therapy and subsequently failed, receive oral anastrozole once daily for 5 years or until progression instead of tamoxifen.

[*For postmenopausal patients, the choice and duration of hormonal therapy given in addition to or an alternative to tamoxifen therapy will be at the physician's discretion]

Patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Being tested
tamoxifen citrate, busulfan, thiotepa, melphalan, aldesleukin
Medical subject headings
Inflammatory Breast Neoplasms, Breast Neoplasms, Male, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tamoxifen citrateDrug

    Also called Nolvadex, TAM, tamoxifen, TMX

    Given orally

  • busulfanDrug

    Also called BSF, BU, Misulfan, Mitosan

    Given orally

  • thiotepaDrug

    Also called Oncotiotepa, STEPA, TESPA, Tespamin

    Given IV

  • melphalanDrug

    Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard

    Given IV

  • aldesleukinBiological

    Also called IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

    Given SC

  • sargramostimBiological

    Also called GM-CSF, Leukine, Prokine

    Given SC

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo autologous peripheral blood stem cell infusion

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    May undergo radiotherapy after completion of IL-2/GM-CSF

Study groups in NCT00003199
Study groupRoleWhat they receive
Arm IExperimentalSee Detailed Description.
Receives: Drug: tamoxifen citrate; Drug: busulfan; Drug: thiotepa; Drug: melphalan; Biological: aldesleukin; Biological: sargramostim; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival

    Event-free survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.

    Measured: 11 years

Secondary outcomes (2)
  1. Overall Survival

    Overall survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.

    Measured: 11 years

  2. Number of Participants With Toxicity of a Combination of Low-dose IL-2 and GM-CSF

    IL-2/GM-CSF toxicity assessed using the NCI Toxicity Criteria. Toxicity was defined as any grade 2, 3, 4 or 5 CNS (except grade 0-3 malaise and fatigue) toxicity; any grade 3, 4, or 5 non-CNS or non-hematological toxicity (except grade 0-3 bilirubin); or any grade 4 or 5 hematological toxicity.

    Measured: 16 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startNov 1997
  3. Primary completionDec 2009
  4. Study completionDec 2009

Resources

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003199
Sponsor's protocol ID
PSOC 1605
Other IDs
NCI-2010-00728
Status last verified
Jun 2017
First submitted
1 Nov 1999
Last updated
12 Jul 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tamoxifen citrate, busulfan and thiotepa in people with Estrogen Receptor-negative Breast Cancer and Estrogen Receptor-positive Breast Cancer, run by Fred Hutchinson 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 15 inclusion and 22 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: finished, as of the sponsor's last update on 12 Jul 2017. 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 17 May 2017). 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?

Event-free Survival (time frame: 11 years). 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 12 Jul 2017.

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