UMCC 9901: Phase II Study of Tailored-Dose Docetaxel + Trastuzumab in Her-2 Positive Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00146042
First received: September 1, 2005
Last updated: October 3, 2012
Last verified: October 2012
  Purpose

This is a research study which aims to improve the way that doctors determine the dose of chemotherapy given to patients. Right now, chemotherapy is determined by a patient's height and weight. However, some patients metabolize chemotherapy faster or slower than the average person because of a different level of drug metabolizing enzyme in the liver. Therefore, some patients are either given too small or too large a dose of chemotherapy because the amount of enzyme is not taken into account. This research study will examine the use of a simple test, call the Erythromycin Breath Test(ERMBT) to determine the amount of enzyme which can metabolize the chemotherapy drug docetaxel (Taxotere). The dose of docetaxel will be tailored to the amount of enzyme which is available to metabolize the drug for each patient. The drug, docetaxel, is combined with another drug, trastuzumab (Herceptin), because at this time this combination appears to be promising in metastatic breast cancer research.


Condition Intervention Phase
HER-2 Positive Metastatic Breast Cancer
Drug: Docetaxel
Drug: Trastuzumab
Procedure: Erythromycin Breath Test (ERMBT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Tailored-Dose Docetaxel + Trastuzumab in Her-2 Positive Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • To assess whether assignment of docetaxel dose based on the ERMBT will result in decreased variability in drug area under the curve when compared to dosing based on body surface area. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • To evaluate the safety and efficacy of tailored-dose docetaxel + trastuzumab in HER-2 neu positive women as first-line treatment in metastatic breast cancer. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • • To evaluate the efficacy of tailored-dose docetaxel + trastuzumab in HER-2 neu positive women, in terms of response rate and time to progression. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • • To explore the relationship between response to therapy and HER-2 status by differential polymerase chain reaction (PCR) vs. protein immunohistochemistry. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: March 1999
Study Completion Date: March 2005
Primary Completion Date: March 2004 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

This is a research study which aims to improve the way that doctors determine the dose of chemotherapy given to patients. Right now, chemotherapy is determined by a patient's height and weight. However, some patients metabolize chemotherapy faster or slower than the average person because of a different level of drug metabolizing enzyme in the liver. Therefore, some patients are either given too small or too large a dose of chemotherapy because the amount of enzyme is not taken into account. This research study will examine the use of a simple test, call the Erythromycin Breath Test(ERMBT) to determine the amount of enzyme which can metabolize the chemotherapy drug docetaxel (Taxotere). The dose of docetaxel will be tailored to the amount of enzyme which is available to metabolize the drug for each patient. The drug, docetaxel, is combined with another drug, trastuzumab (Herceptin), because at this time this combination appears to be promising in metastatic breast cancer research.-Patients participating in this study will have biopsy proven, measurable metastatic breast cancer.

During the study:

  • Patients will receive tailored-dose docetaxel and Trastuzumab for their breast cancer.
  • There are no sex or age restrictions although the patients in this disease category are reflective of an adult female population.

Approximately 30 subjects will be recruited at this site.

Diagnosis and Staging • All patients will have primary tumor measurements by physical exam and/or radiographic studies (CT, MRI, bone scan).

Erythromycin Breath Test*

• The ERMBT will be administered in the outpatient setting, prior to the first cycle of docetaxel. Twenty minutes after the injection of a trace amount of (14C N-methyl) erythromycin, (This test assesses the activity of the cytochrome P450 enzyme which is largely responsible for the metabolism of the chemotherapeutic agent docetaxel.)patients will exhale through a tube creating bubbles in a solution of hyamine hydroxide, ethanol, and a blue indicator until 2 mmol of carbon dioxide has been trapped and the blue color vanishes.

Chemotherapy Regimen

Premedications

  • Dexamethasone 8 mg po bid for three days, beginning the day prior to docetaxel administration.
  • Diphenhydramine 50 mg IVPB
  • Granisetron 2 mg po 30 minutes pre-docetaxel

Chemotherapy

  • Docetaxel, tailored dose, to be infused over 1 hour on day 1 every 3 weeks for the duration of study.
  • Starting dose of docetaxel to be determined by the ERMBT and serum albumin according to formula as stated in protocol (page 11).
  • Trastuzumab, 4 mg/kg to be infused over 90 minutes on day 2 (after pharmacokinetic sampling).
  • Beginning week 2, trastuzumab will be given at a dose of 2 mg/kg weekly throughout duration of study. (After the first dose of docetaxel, future doses may be given on the same day as docetaxel).

Suggested post-chemotherapy antiemetics:

  • Compazine 10 mg po q 6 hours prn nausea/vomiting Pharmacokinetic Analysis
  • All patients will have pharmacokinetic determination with blood drawn for pharmacokinetic analysis over a 24 hour period after the first docetaxel treatment. Time points include time 0, 15 minutes, 45 minutes, 180 minutes (3 hours), 390 minutes (6.5 hours), and 1440 minutes (24 hours).

DEXA Scan*

  • DEXA scan will be performed during the patient's stay in the Clinical Research Center, on the Lunar DPXL Bone Densitometer. This is a very simple and noninvasive test which uses x-rays and a computer program to analyze the ratio of 38 keV to 70 keV attenuation. The program then calculates Fat and Lean values for the arms, legs, abdomen, ribs, and the total body. This is the same test that is in widespread clinical use for the evaluation of osteoporosis. During the DEXA scan, patients will be exposed to a trace amount of radiation which is equal to about 2% of the yearly background dose, or less.

    *The amount of radiation to be administered by the erythromycin breath test and DEXA scan is not medically significant.

  • Patients will receive 2 cycles of docetaxel/trastuzumab and be re-evaluated for response (ever 6 weeks, or later if dosage delays caused lengthening of cycle).
  • Responding and stable patients will continue to receive docetaxel therapy, with evaluations every 2 cycles (every 6 weeks, or later if dosage delays caused lengthening of cycle).
  • Continued treatment beyond 8 cycles will be at the discretion of the patient's primary oncologist.
  Eligibility

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

Inclusion Criteria:

  • Patients with biopsy proven, measurable metastatic breast cancer. Patients with bone-only, and/or effusion-only disease are excluded.
  • HER-2 neu positive by standard immunohistochemical criteria (2+ positivity).
  • No prior chemotherapy for distant metastatic disease.
  • Prior paclitaxel in the adjuvant setting is allowed.
  • Karnofsky performance status equal to 70 or greater.
  • ANC > 1500, Hgb > 10, plt > 100.
  • Patients with some degree of hepatic dysfunction and renal dysfunction are encouraged, in order to evaluate the ability of the ERMBT in tailoring dose in these patient populations.

Exclusion Criteria:

  • Age less than 18 years.
  • Allergy to erythromycin.
  • Previous treatment with docetaxel. Prior paclitaxel is allowed.
  • Grade > 2 peripheral neuropathy.
  • No confounding factors present to provide misinterpretation of data (i.e., concurrent malignancy).
  • Patients who are pregnant or nursing will not be eligible for this protocol. Women of childbearing age who are not practicing reliable birth control must have a documented negative serum HCG.
  • Patients who require concurrent treatment with drugs which are known to induce or inhibit CYP3A activity will be ineligible for the trial. This list includes the drugs midazolam, anti-mycotic agents (ketoconazole and related compounds), macrolide antibiotics (erythromycin and related compounds), nifedipine, anti-seizure drugs, and rifampin (induction).
  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: NCT00146042

Locations
United States, Michigan
University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Genentech
Investigators
Principal Investigator: Anne Schott, MD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00146042     History of Changes
Other Study ID Numbers: UMCC 9901, H1880n
Study First Received: September 1, 2005
Last Updated: October 3, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Trastuzumab
Erythromycin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents
Gastrointestinal Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014