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Stage IV (Metastatic) Breast CancerPhase 1/2NCT00140140

A Phase I/II Study of ABI-007 (Abraxane®, Nab®-Paclitaxel)and Vinorelbine in Patients With Stage IV (Metastatic) Breast Cancer

A Phase 1/2 study testing ABI-007, vinorelbine and Trastuzumab in people with Stage IV (Metastatic) Breast Cancer, run by Celgene at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stage IV (Metastatic) Breast Cancer
What is being tested?
ABI-007, vinorelbine and Trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
2 sitesUnited States
Study dates
Aug 2005to Feb 2008
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient has microscopically confirmed invasive breast carcinoma with clinical and/or radiographic evidence of stage 4 disease. If diagnosis is based on pleural effusion, positive cytology must be confirmed.
  • Patient has had no prior chemotherapy for Stage 4 disease (hormone therapy is permitted). Prior adjuvant paclitaxel by 3-hour infusion is permitted, if there is no residual neuropathy. Prior adjuvant docetaxel on an every 3 week schedule is permitted.
  • Disease must be measurable (unidimensional by Response Evaluation Criteria In Solid Tumors (RECIST) criteria) or evaluable (e.g., malignant effusion, marrow involvement). Elevated tumor markers alone are insufficient.
  • Age >18.
  • Southwest Oncology Group (SWOG)/Eastern Oncology Group (ECOG) performance status must be < or =2 at screen and on treatment day one.
  • Life expectancy must be estimated at >16 weeks.
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  • Prior irradiation is permitted, provided:
  • Does not exceed 25% of the estimated bone marrow volume
  • Measurable/evaluable disease exists outside the radiation field, or progressive disease is documented within the radiation field.
  • Informed consent must be obtained prior to registration.
  • Patients must be > 2 weeks from prior surgery; > 3 weeks from radiation therapy to the pelvis, spine or long bones; > 3 weeks from prior chemotherapy (> 6 weeks for mitomycin C or nitrosureas), or > 2 weeks from prior hormonal therapy.
  • All patients must have placement of appropriate central venous access device.
  • Tumor HER2/neu expression must be determined prior to study enrollment. Assessment may be by fluorescence in situ hybridization (FISH) assay or by immunohistochemistry (ICC). If determination is intermediate by ICC, FISH must be performed. For enrollment purposes, this phase I study will not discriminate based on HER2 status. However, documentation of patients' HER2 status will be maintained and Herceptin will be prescribed for all HER2 positive patients.

Who cannot join

  • Granulocytes < 1,500/mm^3.
  • Platelets < 100,000/mm^3.
  • Hemoglobin < 9 gm/dl.
  • Creatinine > 2.0 mg/dl.
  • Total bilirubin > 2 mg/dl.
  • Visceral crisis characterized by rapidly progressive hepatic or lymphangitic lung metastases.
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  • Medically unstable as judged by the patient's physician.
  • Pregnancy or lactation; failure to employ adequate contraception.
  • Uncontrolled central nervous system (CNS) disease.
  • Pre-existing Grade ≥ 2 peripheral neuropathy except for abnormalities due to cancer.
  • Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol.
  • Prior therapy with vinorelbine or prior therapy with a taxane that resulted in neuropathy.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • City of Hope Comprehensive Cancer Care Center

    Duarte, California, 91010

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: An Open-Label Phase I/II Study of Weekly ABI-007 and Vinorelbine With or Without G-CSF in Patients With Stage IV (Metastatic) Breast Cancer

The purpose of this study is to: 1) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the absence of planned growth factor support with granulocyte colony-stimulating factor (G-CSF) (Patients with HER-2/neu positive disease may receive Herceptin, and 2) determine the optimal tolerated dose of ABI-007 and vinorelbine, given concurrently on a weekly basis, in the presence of planned growth factor support with G-CSF.

Being tested
ABI-007, vinorelbine, Trastuzumab, G-CSF
Keywords
Breast cancer
Medical subject headings
Neoplasm Metastasis, Breast Neoplasms

What participants receive

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

  • ABI-007Drug

    Also called Abraxane®, Nab®-Paclitaxel, paclitaxel protein-bound particles for injectable suspension

    Weekly intravenous infusions over 30 minutes.

  • vinorelbineDrug

    Also called Navelbine, vinorelbine tartrate, 5'noranhydrovinblastine

    Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.

  • TrastuzumabDrug

    Also called Herceptin

    Trastuzumab was administered to participants who had HER-2-neu positive tumors. Participants received trastuzumab by IV infusion via a vascular access device following dosing with ABI-007 and vinorelbine. During their first cycle, 4 mg/kg was administered on day 1 of that cycle as a loading dose. During subsequent weekly treatments, 2 mg/kg was administered.

    Trastuzumab is commercially available and was not supplied by the Sponsor.

  • G-CSFBiological

    Also called granulocyte-colony stimulating factor

    During Part 1, participants followed a dosing regimen with ABI-007 and vinorelbine without G-CSF treatment. However, G-CSF was allowed for administration as necessary in accordance with commonly accepted clinical guidelines.

    In Part 2, participants started G-CSF treatment in concurrence with their ABI-007 and vinorelbine treatments. G-CSF was administered to all participants on Days 2-7 of each cycle, at a dose of 5 mcg/kg. If the participant's absolute neutrophil (ANC) count was >20,000/mm^3 on the day of anticipated chemotherapy, the site staff reduced the daily dose of G-CSF by 50% to 2.5 mcg/kg.

    G-CSF is commercially available and was not supplied by the Sponsor.

Study groups in NCT00140140
Study groupRoleWhat they receive
Part 1: 80 mg ABI-007 + 15 mg vinorelbineExperimentalWeekly intravenous infusion of 80 mg/m^2 ABI-007, followed by an infusion of 15 mg/m^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. No G-CSF support was planned.
Receives: Drug: ABI-007; Drug: vinorelbine; Drug: Trastuzumab
Part 2: 80 mg ABI-007 + 15 mg vinorelbineExperimentalWeekly intravenous infusion of 80 mg/m^2 ABI-007, followed by an infusion of 15 mg/m^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Receives: Drug: ABI-007; Drug: vinorelbine; Drug: Trastuzumab; Biological: G-CSF
Part 2: 90 mg ABI-007 + 20 mg vinorelbineExperimentalWeekly intravenous infusion of 90 mg/m^2 ABI-007, followed by an infusion of 20 mg/m^2 vinorelbine. Participants with human epidermal growth factor receptor 2-positive (HER2+) and who met cardiac safety requirements were also administered weekly Herceptin® (trastuzumab) following completion of ABI-007 and vinorelbine infusions. G-CSF support was given.
Receives: Drug: ABI-007; Drug: vinorelbine; Drug: Trastuzumab; Biological: G-CSF

What is being measured

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

  1. Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)

    Overall response rate (ORR) is complete response (CR) + partial response (PR). Complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation.

    Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

    Measured: up to month 30

  2. Participants With Dose Limiting Toxicities

    Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Any drug-related toxicities CTC Grade 3 or higher were considered dose limiting. Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death. Other conditions considered dose-limiting toxicities include:

    • requirement of a dose adjustment during the first 4 weeks
    • a dose delay of >3 weeks during the first 4 weeks Grade 3 or greater toxicities attributed to the use of Herceptin were not considered dose-limiting toxicities.

    The optimal tolerated dose of ABI-007 and vinorelbine given concurrently was defined as the dose administered in the absence of DLTs.

    Measured: up to month 1

  3. Percentage of Participants With Discontinued, Delayed or Interrupted Therapy

    Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.

    Measured: up to week 129

  4. Participant Counts of the Most Severe Grade for Absolute Neutrophil (ANC), White Blood Cell (WBC), Platelet, and Hemoglobin Counts as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Experience (NCI CTCAE v3)

    Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest measured (nadir) blood counts were graded using NCI CTCAE version 3.

    ANC:

    Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 1.5*10^9/L; Grade 2 = <1.5 - 1.0*10^9/L; Grade 3 = <1.0 - 0.5*10^9/L; Grade 4 = <0.5*10^9/L

    WBC:

    Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 3.0*10^9/L; Grade 2 = <3.0 - 2.0*10^9/L; Grade 3 = <2.0 - 1.0*10^9/L; Grade 4 = <1.0*10^9/L

    Platelets:

    Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 75.0*10^9/L; Grade 2 = <75.0 - 50.0*10^9/L; Grade 3 = <50.0 - 25.0*10^9/L; Grade 4 = <25.0*10^9/L

    Hemoglobin:

    Grade 0 = within normal limits; Grade 1 = < lower limit of normal - 100 g/L ; Grade 2 = <100 - 80 g/L; Grade 3 = <80 - 65 g/L; Grade 4 = <65 g/L

    Measured: up to week 129 (longest treatment)

  5. Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count

    Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.

    Measured: up to week 129 (longest treatment)

  6. Nadir Measurement for Hemoglobin (Hgb)

    Myelosuppression is a decrease in the ability of the bone marrow to produce blood cells. The lowest observed measurement is the nadir. Blood counts were performed each week of treatment.

    Measured: up to week 129 (longest treatment)

Secondary outcomes (5)

  1. Percentage of Participants With Stable Disease for >= 16 Weeks, or Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0)

    Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). See Outcome #1 for definitions of CR and PR.

    RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

    Measured: up to month 30

  2. Kaplan Meier Estimate for Time to Disease Progression (TTP)

    Time to progression was defined as the time from the first dose of study drug to the start of progression. Participants that did not have progression were censored at the last known time the patient was evaluated for progression. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

    Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

    Measured: up to month 30

  3. Kaplan-Meier Estimate for Duration of Response

    Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first. Patients that did not have progression or have not died were censored at the last known time the patient was progression free. Patients that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

    Complete response (CR) and partial response (PR) are defined in outcome #1. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

    Measured: up to month 30

  4. Kaplan Meier Estimate for Progression-Free Survival (PFS)

    PFS was defined as the time from the first dose of study drug to the start of progression or patient death (any cause) whichever occurred first. Participants that did not have progression or have not died were censored at the last known time the participant was progression free. Participants that initiate other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated.

    Because no patients died as a result of a non-disease progression event, the analysis of PFS was identical to the analysis for TTP.

    Measured: up to month 30

  5. Kaplan-Meier Estimates for Participant Survival

    Participant survival is the time from the first dose of study drug to participant death from any cause. Participants that did not die were censored at the last known time the participant was alive.

    Measured: up to 39 months

Timeline

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

  1. First posted1 Sep 2005 (estimated)
  2. Study startAug 2005
  3. Primary completionFeb 2008
  4. Study completionFeb 2008

Why it stopped: Unable to determine the optimum tolerated dose

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00140140
Sponsor's protocol ID
CA025
Status last verified
Nov 2019
First submitted
30 Aug 2005
Last updated
26 Nov 2019
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ABI-007, vinorelbine and Trastuzumab in people with Stage IV (Metastatic) Breast Cancer, run by Celgene at 2 sites 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 13 inclusion and 12 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 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 24 Oct 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?

Participants With Confirmed Complete or Partial Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0) (time frame: up to month 30). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00140140.

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 26 Nov 2019.

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