Clinical trial NCT00041470
Conditions: Breast Cancer
Sponsor: University of Washington
Start date: 2001-03-01; Completion date: 2008-08-01
Enrollment: 38 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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;

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.

Arms: arm 1: 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
Interventions: intervention 1: Paclitaxel intervention 2: Vinorelbine intervention 3: Herceptin intervention 4: Filgrastim
Intervention descriptions: intervention 1: 50 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment. intervention 2: 20 mg/m2 IV weekly. Treatment continues until disease progression, excessive toxicity or other reason to remove the patient from protocol treatment. intervention 3: 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. intervention 4: 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.

Protocol documents: