Personalized Treatment Selection for Metastatic Breast Cancer
This study has been completed.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
First received: October 24, 2008
Last updated: May 30, 2014
Last verified: May 2014
The goal of this clinical research study is to learn if researchers can use genetic tests to predict who may benefit from treatment with SprycelTM (dasatinib) or selumetinib (AZD6244).
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Personalized Treatment Selection for Metastatic Breast Cancer
Primary Outcome Measures:
- Clinical benefit rate (CB = objective tumor response or stable disease > 6 months) [ Time Frame: Evaluation within 7 days before starting each cycle of therapy (i.e. every 28 days) ] [ Designated as safety issue: No ]
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence
| Study Start Date:
| Primary Completion Date:
||May 2014 (Final data collection date for primary outcome measure)
Experimental: Dasatinib (Sprycel)
Patients who are predicted to respond to dasatinib by any one of the three predictors receive dasatinib 100 mg by mouth daily (QD).
100 mg tablet by mouth daily
Experimental: AZD6244 (Selumetinib)
Patients who are predicted to respond to selumetinib/AZD6244 receive selumetinib 75 mg by mouth twice daily (BID), a marker-negative control group for the MEK activity signature also receive selumetinib 75 mg by mouth twice daily.
75 mg by mouth twice daily.
Other Name: Selumetinib
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- (Turnstile One - Applies only to inclusion criteria 1 - 4): Histologically confirmed breast cancer and evidence of metastatic disease that can be biopsied with acceptable risk. Patients must agree to mandatory fine needle aspiration of the cancer for response marker determination. Patient must have a positive gene expression profile. Positive gene expression signature obtained separately on trial LAB11-0337 will also be acceptable for eligibility.
- Patients must have measurable or evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- Subject, age > 18 years (the safety and efficacy of dasatinib and the appropriate dose has not been established for children).
- Signed written informed consent including a HIPAA form according to institutional guidelines.
- (Turnstile Two Applies Only to Inclusion Criteria 5 -17) - Therapy with Dasatinib - Patient must have a positive gene expression profile. Positive gene expression obtained separately on trial LAB11-0337 will also be acceptable for eligibility.
- Performance status Zubrod scale 0-2 (Appendix B) within 8 days of starting therapy.
- Full physical examination and history including documentation of weight, height, and vital signs within 8 days of starting therapy.
- Patients may have received any number of previous therapies for metastatic breast cancer. Patients must have received, had a contraindication to, or declined treatment with an anthracycline and taxane (and Herceptin if HER-2 positive) in either the adjuvant or metastatic setting.
- Adequate organ function assessed within 14 days of study therapy, defined as: (a)Total bilirubin </= 2.0 times the institutional Upper Limit of Normal (ULN); (b) Hepatic enzymes (AST, ALT ) </= 2.5 times the institutional ULN; (c) Serum Na, K+, Mg2+, Phosphate and Ca2+ >/= lower limit of normal (LLN); (d) Serum Creatinine < 1.5 time the institutional ULN; and (e) Hemoglobin, Neutrophil count, Platelets, PT, PTT all Grade 0-1.
- A baseline EKG within 14 days of starting therapy, with a QTc interval not > 460 msec in women, or > 450 in men.
- Ability to take oral medication (dasatinib must be swallowed whole).
- Patient must agree to discontinue St. Johns Wort while receiving dasatinib therapy if previously taken.
- Patient must agree that IV bisphosphonate therapy will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia. (After the need for Ca2+ supplementation has been assessed and levels documented to be >LLN, subjects on prior bisphosphonate may be restarted with caution at the investigator's discretion).
- Females of childbearing potential must have a negative serum pregnancy test within 7 days of starting therapy.
- Persons of reproductive potential must agree to use and utilize a barrier method of contraception throughout treatment and for at least 4 weeks after study drug is stopped.
- Concurrent medications must be assessed, and patient must agree to discontinue all restricted medications within 7 days of starting therapy.
- Stable brain metastasis for at least 3 months
- (Only turnstile II applies to Exclusion Criteria): Known allergy to study drug.
- Concurrent medical condition which may increase the risk of toxicity, including: (a) pleural or pericardial effusion of any grade; (b) uncontrolled angina, congestive heart failure or MI within (6 months); (c) history of congenital long QT syndrome or prolonged QTc interval on pre-entry electrocardiogram > 460 msec in women and >450 msec. in men; (d) any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes); continued in excl # 3
- Continued from exclusion # 2: (e) subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration; (f) history of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) or acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); (g) ongoing or recent (3 months) significant gastrointestinal bleeding
- Concomitant medications with any of the following drugs should be considered for exclusion unless discontinued 7 days prior to starting dasatinib: (a) Category I drugs that prolong QT interval and are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycin, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, and domperidone. Cont. in exclusion # 5
- Continued from exclusion criterion # 4: halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
- CYP3A4 inhibitors. Dasatinib is primarily metabolized by the CYP3A4 enzyme. Therefore, potent inhibitors of CYP3A4 may increase dasatinib plasma concentrations: (i) ketoconazole, itraconazole, erythromycin, clarithromycin,ritonavir, atazanavir, indinavir, nefazodone, nelfinavir, saquinavir; (ii) telithromycin; and (iii) subjects should be advised not to consume substantial quantities of grapefruit juice.
- Medications which durably inhibit platelet function or inhibit anticoagulation. Medications which directly and durably inhibit platelet function or coagulation include: (i) aspirin or aspirin-containing combinations, clopidogrel, dipyridamole, tirofiban, dipyridamole, epoprostenol, eptifibatide, cilostazol, abciximab, ticlopidine, cilostazol; and (ii) warfarin, heparin/low molecular weight heparin [e.g., danaparoid, dalteparin, tinzaparin, enoxaparin]. Exceptions: low-dose warfarin for prophylaxis to prevent catheter thrombosis, and heparin for flushes of IV lines is allowed.
- Women who are unwilling or unable to use a barrier method of contraception to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breast-feeding. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
- Exclusion from Selumetinib therapy include Uncontrolled hypertension (BP >/=150/95 mmHg), Heart failure (NYHA >/= Class II), prior or current cardiomyopathy (LVEF </= 50%), Atrial fibrillation (heart rate >100 bpm), Unstable ischaemic heart disease (MI within 6 months prior, or angina requiring use of nitrates more than once weekly).
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00780676
|UT MD Anderson Cancer Center
|Houston, Texas, United States, 77030 |
M.D. Anderson Cancer Center
||Stacy Moulder, MD
||UT MD Anderson Cancer Center
No publications provided
||M.D. Anderson Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 24, 2008
||May 30, 2014
||United States: Food and Drug Administration
Keywords provided by M.D. Anderson Cancer Center:
Metastatic Breast Cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 22, 2014
Neoplasms by Site
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action