Navelbine, Taxol, Herceptin and Neupogen in Stage IV Breast Cancer: A Phase I - II Trial

NCT00041470 | Terminated Phase 1 Results

• 1 other identifier: 18245
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this are:

• To determine the highest doses of Taxol and Navelbine that we can safely give to patients;
• To determine what kind of side effects are caused by the combination of Taxol, Navelbine and G-CSF;
• To determine whether the combination of Taxol, Navelbine and G-CSF is more effective than standard therapy in treating metastatic breast cancer and prolonging life;

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To Measure Response Rates, Time to Progression and Survival in Patients so Treated.

  1 year

Secondary Outcomes (1)

• To Measure the Qualitative and Quantitative Toxicity of This Regimen.

  <=18 months

Study Arms (1)

Weekly paclitaxel, vinorelbine and GCSF

EXPERIMENTAL

Weekly paclitaxel (50 mg/m2 IV) and weekly vinorelbine (20 mg/m2 IV) with daily G-CSF support and Herceptin for patients with HER-2/neu positive disease. Paclitaxel weekly. Dose levels: 50 mg/m2, 60 mg/m2, 70 mg/m2, 80 mg/m2 Vinorelbine (Navelbine) administered one hour after paclitaxel, weekly. Dose levels: 20 mg/m2, 22.5 mg/m2, 25 mg/m2, 27.5 mg/m2 Patients who are HER-2+ and IV infusion. Herceptin 4 mg/kg IV given only on day 1 of the first cycle. Herceptin 2 mg/kg IV, maintenance dose will be given every week starting with week 2. G-CSF (filgrastim, Neupogen) 5 mg/kg/day s.c., administered daily

Drug: Paclitaxel; Drug: Vinorelbine; Drug: Herceptin; Drug: Filgrastim

Interventions

Paclitaxel DRUG

50 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.

Also known as: Taxol

Weekly paclitaxel, vinorelbine and GCSF

Vinorelbine DRUG

20 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.

Also known as: Navelbine

Weekly paclitaxel, vinorelbine and GCSF

Herceptin DRUG

4 mg/kg IV loading dose day 1 of first week followed by 2 mg/kg IV maintenance dose on each subsequent week. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.

Also known as: Trastuzumab

Weekly paclitaxel, vinorelbine and GCSF

Filgrastim DRUG

5 mcg/kg daily including the day of IV chemotherapy. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.

Also known as: G-CSF, Neupogen

Weekly paclitaxel, vinorelbine and GCSF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has stage IV, microscopically-confirmed carcinoma of the breast with histologic slides and/or blocks available for review.
• Patient has had one or less prior regimens for metastatic disease. Prior paclitaxel by 3, 24 or 96-hour infusion is permitted as long as it did not result in any neuropathy. Prior docetaxel on an every 3-week schedule is permitted.
• Measurable (bidimensionally) or evaluable disease.
• Age \> 18.
• Karnofsky Performance Status \> 70% (ECOG, \< 2) at screen and on the first day of treatment.
• Life expectancy \> 16 weeks.
• Prior irradiation is permitted, provided:
• Prior irradiation does not exceed 25% of the estimated bone marrow volume. (See Appendix I)
• Measurable/evaluable disease must exist outside the radiation field OR there must be histologic proof of progressive disease within a 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 hydridization (FISH) assay or by immunohistochemistry (ICC). If determination is intermediate by ICC, FISH must be performed. For enrollment purposes, the phase I portion of the 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. The phase II portion of the study will enroll 30 patients who are documented HER2 overexpressors and 30 patients who are non-overexpressors.

You may not qualify if:

• Granulocytes \< 1,500/mm3.
• Platelets \< 100,000/mm3.
• 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 CNS disease.
• Pre-existing clinically significant 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.
• Known hypersensitivity to E. coli-derived proteins, Filgrastim, or any component of the product as Neupogen® is contraindicated in such subjects.

Sponsors & Collaborators

• University of Washington: lead
• Amgen: collaborator
• Bristol-Myers Squibb: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Vinorelbine; Trastuzumab; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Julie Gralow, MD
• Organization: University of Washington

pink@u.washington.edu

206-288-2053

Study Officials

• Julie R. Gralow, M.D.

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Medicine/Oncology

Study Record Dates

• First Submitted: July 9, 2002
• First Posted: July 10, 2002
• Study Start: March 1, 2001
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: July 17, 2017
• Results First Posted: June 6, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)