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Study Summary
No. 2007-0766:.......Breast......Vicente Valero......Breast Medical Oncology
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Study Summary Title
Study Summary
Number:
2007-0766
Study Title:A Phase I-II Study of R115777 (Tipifarnib, Zarnestra) Plus Sequential Weekly Paclitaxel followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients with Stage IIB-IIIC Breast Cancer
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Physician New Patient Referral
Name:Vicente ValeroPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Breast Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2817
Contact us about clinical trials
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General Information
Disease Group:BreastSupported By:NCI
Phase of Study:Phase I/Phase IIReturn
Visit:
Weekly for 12 weeks and again every 2 weeks for 4 cycles
Treatment
Agents:
Cyclophosphamide
Doxorubicin
Filgrastim
Paclitaxel
Pegfilgrastim
Tipifarnib
Home Care:N/A
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is find the highest tolerable dose of
Zarnestra (tipifarnib), combined with chemotherapy (paclitaxel, doxorubicin,
and cyclophosphamide), that can be given to patients with locally advanced
breast cancer. Researchers want to find out the effect of tipifarnib plus
chemotherapy on tumor cells and normal breast tissue. Researchers want to
learn how often the signs of cancer are no longer able to be detected in the
breast and lymph nodes by the time the participant has a mastectomy or
lumpectomy. The safety of this drug combination will also be studied.

The Phase 1 portion of this study is finished. If you choose to take part in
this study, you will be enrolled in the Phase 2 portion. The goal of the Phase
2 portion of the study is to find out if this drug combination is effective in
treating locally advanced breast cancer. The safety of the treatment
combination will also be studied.
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Study Objectives / Outcomes
Primary Objectives:
  • To determine the recommended phase II dose of tipifarnib given weekly for 3 of 7 days when combined with weekly paclitaxel (phase I portion of trial)
  • To determine the pathologic complete remission rate (including breast and breast plus axillary nodes) after sequential weekly paclitaxel plus tipifarnib x 12 cycles followed by doxorubicin/cyclophosphamide plus tipifarnib x 4 cycles in patients with clinical stage IIB-IIIC breast cancer (phase II portion). One cycle of paclitaxel is equivalent to one week of treatment.
  • To determine the feasibility and safety of the combination of sequential weekly paclitaxel plus tipifarnib x 12 cycles, followed by doxorubicin/cyclophosphamide plus tipifarnib x 4 cycles (phase I and II portion)

Secondary Objectives:
  • Laboratory objectives:
  • To correlate pre-treatment levels of ErbB1,2,3,4, and phosphorylated levels of Akt, STAT3, Erk1/2 to clinical response, and percent inhibition of proliferation (Ki-67) and percent induction of apoptosis (Tunel) in the post-treatment tumor specimen (Sebti lab).
  • To correlate the percent decrease in the levels of farnesyltransferase FTase activity, HDJ-2 farnesylation, phospho-Akt, phospho-STAT3, Rho C, and phospho-Erk 1-2 with clinical response rates, percent inhibition of proliferation (Ki-67) and percent inhibition of apoptosis (Tunel) (Sebti lab).
  • To perform microarray analysis on pre- and post-treatment fresh tumor specimens when sufficient RNA (10-20 µg) is available (Sebti lab).
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Study Status Information
Study Activation / Registration Date:04/23/2008
IRB Review and Approval Date:04/23/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:86
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC. The tumor must be estrogen and/or progesterone receptor positive, and Her2/neu negative (by DAKO Herceptest or FISH). Only patients with inflammatory breast cancer (IBC) will be enrolled onto this study at UTMDACC. Patients with IBC must have HER2 negative, and hormone receptor positive or negative.

2) No prior chemotherapy, irradiation, or definitive therapeutic surgery (eg, mastectomy or lumpectomy or axillary dissection) for this malignancy. Patients who have had a prior sentinel lymph node biopsy for this malignancy are eligible.

3) Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indications (e.g., osteoporosis, prior DCIS) are eligible. Tamoxifen therapy or other SERMs should be discontinued at least 1 week before the patient is enrolled on this study.

4) Age >/= 18 years. Because breast carcinoma is a disease of adults that rarely occurs in children, children are excluded from this study.

5) ECOG performance status 0 or 1.

6) Patients must have normal organ and marrow function as defined below: - leukocytes >/= 3,000/µl - absolute neutrophil count >/= 1,500/µl - platelets >/= 100,000/µl - total bilirubin within normal institutional limits - AST(SGOT)/ALT(SGPT) </= 2.5 X institutional upper limit of normal - left ventricular ejection fraction within normal institutional limits - creatinine within normal institutional limits OR - creatinine clearance >/= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Continued in Inclusion 7).

7) Continued from Inclusion 6). - left ventricular ejection fraction at or above institutional lower limits of normal (by echocardiogram or nuclear scan within 12 weeks of registration) - pulmonary function tests demonstrating an FEV1 >/= 1 liter and DLCO >/=50% (required within 4 weeks of registration) only if baseline CT of chest shows parenchymal lung disease, or there is a history of COPD or other pulmonary disease

8) Patients must be disease-free of prior invasive malignancies for >/= 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix. Patient with the following prior or concurrent diagnoses are eligible: lobular carcinoma in situ, contralateral ductal carcinoma in situ, or contralateral invasive ductal and/or lobular cancer (an no prior adjuvant chemotherapy for previous breast malignancy).

9) The effects of tipifarnib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

10) Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:1) Patients may not be receiving any other investigational agents.

2) History of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib or other agents used in the study (e.g., imidazoles, quinolones).

3) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that woul d limit compliance with study requirements.

4) Pregnant women are excluded from this study the effects of tipifarnib on the developing human fetus at the recommended therapeutic dose are unknown. Because there is also an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tipifarnib, breastfeedi ng should be discontinued if the mother is treated with tipifarnib. These potential risks may also apply to other agents used in this study.

5) Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with tipifarnib or other agents adm inistered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

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Links
Registration Number: NCT00470301
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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