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

This study has been terminated.
(Unable to determine the optimum tolerated dose)
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00140140
First received: August 30, 2005
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Stage IV (Metastatic) Breast Cancer
Drug: ABI-007
Drug: vinorelbine
Drug: Trastuzumab
Biological: G-CSF
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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.


  • Participants With Dose Limiting Toxicities [ Time Frame: up to month 1 ] [ Designated as safety issue: Yes ]

    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.


  • Percentage of Participants With Discontinued, Delayed or Interrupted Therapy [ Time Frame: up to week 129 ] [ Designated as safety issue: Yes ]
    Percentage of participants who had discontinued therapy or had a delayed dose or an interrupted (omitted) dose due to toxicities/adverse events.

  • 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) [ Time Frame: up to week 129 (longest treatment) ] [ Designated as safety issue: Yes ]

    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


  • Nadir Measurement for Absolute Neutrophil (ANC), White Blood Cell (WBC) and Platelet Count [ Time Frame: up to week 129 (longest treatment) ] [ Designated as safety issue: Yes ]
    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.

  • Nadir Measurement for Hemoglobin (Hgb) [ Time Frame: up to week 129 (longest treatment) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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) [ Time Frame: up to month 30 ] [ Designated as safety issue: No ]

    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.


  • Kaplan Meier Estimate for Time to Disease Progression (TTP) [ Time Frame: up to month 30 ] [ Designated as safety issue: No ]

    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.


  • Kaplan-Meier Estimate for Duration of Response [ Time Frame: up to month 30 ] [ Designated as safety issue: No ]

    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.


  • Kaplan Meier Estimate for Progression-Free Survival (PFS) [ Time Frame: up to month 30 ] [ Designated as safety issue: No ]

    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.


  • Kaplan-Meier Estimates for Participant Survival [ Time Frame: up to 39 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 16
Study Start Date: August 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: 80 mg ABI-007 + 15 mg vinorelbine
Weekly 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.
Drug: ABI-007
Weekly intravenous infusions over 30 minutes.
Other Names:
  • Abraxane®
  • Nab®-Paclitaxel
  • paclitaxel protein-bound particles for injectable suspension
Drug: vinorelbine
Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.
Other Names:
  • Navelbine
  • vinorelbine tartrate
  • 5'noranhydrovinblastine
Drug: Trastuzumab

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.

Other Name: Herceptin
Experimental: Part 2: 80 mg ABI-007 + 15 mg vinorelbine
Weekly 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.
Drug: ABI-007
Weekly intravenous infusions over 30 minutes.
Other Names:
  • Abraxane®
  • Nab®-Paclitaxel
  • paclitaxel protein-bound particles for injectable suspension
Drug: vinorelbine
Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.
Other Names:
  • Navelbine
  • vinorelbine tartrate
  • 5'noranhydrovinblastine
Drug: Trastuzumab

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.

Other Name: Herceptin
Biological: G-CSF

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.

Other Name: granulocyte-colony stimulating factor
Experimental: Part 2: 90 mg ABI-007 + 20 mg vinorelbine
Weekly 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.
Drug: ABI-007
Weekly intravenous infusions over 30 minutes.
Other Names:
  • Abraxane®
  • Nab®-Paclitaxel
  • paclitaxel protein-bound particles for injectable suspension
Drug: vinorelbine
Weekly intravenous infusions over 10-30 minutes, immediately after ABI-007. Vinorelbine is commercially available and was not supplied by the Sponsor.
Other Names:
  • Navelbine
  • vinorelbine tartrate
  • 5'noranhydrovinblastine
Drug: Trastuzumab

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.

Other Name: Herceptin
Biological: G-CSF

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.

Other Name: granulocyte-colony stimulating factor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00140140

Locations
United States, California
City of Hope Comprehensive Cancer Care Center
Duarte, California, United States, 91010
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00140140     History of Changes
Other Study ID Numbers: CA025
Study First Received: August 30, 2005
Results First Received: August 20, 2013
Last Updated: August 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Celgene Corporation:
Breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Vinorelbine
Vinblastine
Trastuzumab
Lenograstim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014