Breast CancerPhase 1/2NCT00041470
Navelbine, Taxol, Herceptin and Neupogen in Stage IV Breast Cancer: A Phase I - II Trial
A Phase 1/2 study testing Paclitaxel, Vinorelbine and Herceptin in people with Breast Cancer, run by University of Washington at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Paclitaxel, Vinorelbine and Herceptin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2001to Aug 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 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Cancer Care Alliance
Seattle, Washington, 98109-1023
About this study
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;
Read the detailed description
Complete response (CR) in advanced breast cancer is an important predictor of improved survival. The largest experience reported with long-term follow-up in this regard is from M.D. Anderson Hospital, with a median survival of 33 months and 5-year survival of 19% among patients who achieved a CR with doxorubicin-based chemotherapy.19 We believe that our institutional experience to date indicates that CR rates in excess of 20% can be achieved in second-line chemotherapy from the combination of vinorelbine and a taxane, provided that G-CSF is given. For the reasons outlined, we believe that dose density is likely to be important for both classes of agents, but dose intensity may be most important for vinorelbine. Both paclitaxel and docetaxel can be given on a weekly schedule with some success, but it appears that myelosuppression is a more frequent dose-limiting toxicity on this schedule for docetaxel. For the current trial, we therefore propose to study weekly paclitaxel in combination with dose-intensive vinorelbine, utilizing continuous G-CSF support as in our prior studies. We believe that starting doses of 60 mg/m2 for paclitaxel and 20 mg/m2 for vinorelbine will be well tolerated, but our experience to date, treating 3 patients off study at these doses without G-CSF support, indicates that some will require G-CSF even at this dose level: we observed grade 4 neutropenia in 2 of the 3. Our intention in this trial is to determine the optimal dose of these two agents when continuous growth factor support is provided. We will be starting at a ratio of 0.8 for vinorelbine and 0.75 for paclitaxel (assuming 80 mg/m2/week as a "full" dose for the later agent).
It is now widely appreciated that patients with metastatic breast cancer whose tumors over express HER-2-neu demonstrate benefit from the addition of trastuzumab (Herceptin) to a chemotherapy program with paclitaxel as a single agent.20 Such patients will be allowed to receive trastuzumab in the standard dose and schedule (4 mg/kg loading dose, then 2 mg/kg/week) given IV, in addition to paclitaxel and vinorelbine. Since trastuzumab does not produce myelosuppression or neuropathy (the anticipated dose-limiting toxicities for vinorelbine and paclitaxel, respectively), and neither of these agents combined separately with trastuzumab produces unusual or severe new side effects, this should not affect the dose escalation scheme for the chemotherapeutic agents.
- Conditions
- Breast Cancer
- Being tested
- Paclitaxel, Vinorelbine, Herceptin, Filgrastim
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Also called Taxol
50 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.
VinorelbineDrug
Also called Navelbine
20 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment.
HerceptinDrug
Also called Trastuzumab
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.
FilgrastimDrug
Also called G-CSF, Neupogen
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Paclitaxel; Drug: Vinorelbine; Drug: Herceptin; Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Measure Response Rates, Time to Progression and Survival in Patients so Treated.
Measured: 1 year
Secondary outcomes (1)
To Measure the Qualitative and Quantitative Toxicity of This Regimen.
Measured: <=18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2002 (estimated)
- Study startMar 2001
- Primary completionAug 2008
- Study completionAug 2008
Why it stopped: Sponsor withdrew the study
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 University of WashingtonThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Bristol-Myers Squibb, GlaxoSmithKline
- Responsible party
- Principal investigator, Julie Ruth Gralow, University of Washington
- Investigators
- Julie R. Gralow, M.D., Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00041470
- Sponsor's protocol ID
- 18245
- Status last verified
- Jun 2017
- First submitted
- 9 Jul 2002
- Last updated
- 17 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Navelbine, Taxol, Herceptin and Neupogen in Stage IV Breast Cancer: A Phase I - II Trial
- ClinicalTrials.gov ID
- NCT00041470
- Acronym / sponsor ID
- 18245
- Conditions
- Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor withdrew the study
- Enrolment
- 38 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Amgen, Bristol-Myers Squibb, GlaxoSmithKline
- Study start
- Mar 2001
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 10 Jul 2002 (estimated)
- Results
- Posted 6 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
Detailed description
Complete response (CR) in advanced breast cancer is an important predictor of improved survival. The largest experience reported with long-term follow-up in this regard is from M.D. Anderson Hospital, with a median survival of 33 months and 5-year survival of 19% among patients who achieved a CR with doxorubicin-based chemotherapy.19 We believe that our institutional experience to date indicates that CR rates in excess of 20% can be achieved in second-line chemotherapy from the combination of vinorelbine and a taxane, provided that G-CSF is given. For the reasons outlined, we believe that dose density is likely to be important for both classes of agents, but dose intensity may be most important for vinorelbine. Both paclitaxel and docetaxel can be given on a weekly schedule with some success, but it appears that myelosuppression is a more frequent dose-limiting toxicity on this schedule for docetaxel. For the current trial, we therefore propose to study weekly paclitaxel in combination with dose-intensive vinorelbine, utilizing continuous G-CSF support as in our prior studies. We believe that starting doses of 60 mg/m2 for paclitaxel and 20 mg/m2 for vinorelbine will be well tolerated, but our experience to date, treating 3 patients off study at these doses without G-CSF support, indicates that some will require G-CSF even at this dose level: we observed grade 4 neutropenia in 2 of the 3. Our intention in this trial is to determine the optimal dose of these two agents when continuous growth factor support is provided. We will be starting at a ratio of 0.8 for vinorelbine and 0.75 for paclitaxel (assuming 80 mg/m2/week as a "full" dose for the later agent).
It is now widely appreciated that patients with metastatic breast cancer whose tumors over express HER-2-neu demonstrate benefit from the addition of trastuzumab (Herceptin) to a chemotherapy program with paclitaxel as a single agent.20 Such patients will be allowed to receive trastuzumab in the standard dose and schedule (4 mg/kg loading dose, then 2 mg/kg/week) given IV, in addition to paclitaxel and vinorelbine. Since trastuzumab does not produce myelosuppression or neuropathy (the anticipated dose-limiting toxicities for vinorelbine and paclitaxel, respectively), and neither of these agents combined separately with trastuzumab produces unusual or severe new side effects, this should not affect the dose escalation scheme for the chemotherapeutic agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Weekly paclitaxel, vinorelbine and GCSF | Experimental | Drug: Paclitaxel, Drug: Vinorelbine, Drug: Herceptin, Drug: FilgrastimWeekly 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (13 listed)
- Granulocytes < 1,500/mm3.
- Platelets < 100,000/mm3.
- Hemoglobin < 9 gm/dl.
- Creatinine > 2.0 mg/dl.
- Total bilirubin > 2 mg/dl.
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 |
|---|---|---|
| PaclitaxelAlso: Taxol50 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment. | Drug | Weekly paclitaxel, vinorelbine and GCSF |
| VinorelbineAlso: Navelbine20 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment. | Drug | Weekly paclitaxel, vinorelbine and GCSF |
| HerceptinAlso: Trastuzumab4 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. | Drug | Weekly paclitaxel, vinorelbine and GCSF |
| FilgrastimAlso: G-CSF, Neupogen5 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. | Drug | Weekly paclitaxel, vinorelbine and GCSF |
Primary outcome
To Measure Response Rates, Time to Progression and Survival in Patients so Treated.
Time frame: 1 year
1 secondary outcome
To Measure the Qualitative and Quantitative Toxicity of This Regimen.
Time frame: <=18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Julie R. Gralow, M.D. principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Paclitaxel, Vinorelbine and Herceptin in people with Breast Cancer, run by University of Washington 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 13 inclusion and 13 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 17 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 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 6 Jun 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?
To Measure Response Rates, Time to Progression and Survival in Patients so Treated. (time frame: 1 year). 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 17 Jul 2017.