- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01251874
Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer
A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer
Studieöversikt
Status
Betingelser
- BRCA1 genmutation
- BRCA2 genmutation
- Återkommande bröstkarcinom
- Östrogenreceptornegativ
- Östrogenreceptor positiv
- HER2/Neu negativ
- Progesteronreceptornegativ
- Progesteronreceptor positiv
- Trippelnegativt bröstkarcinom
- Steg IV Bröstcancer AJCC v6 och v7
- Steg IIIB Bröstcancer AJCC v7
- Steg IIIC Bröstcancer AJCC v7
Detaljerad beskrivning
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose of veliparib along with carboplatin on a 14-day and 21-day schedule in patients with Her2 negative metastatic breast cancer that are estrogen receptor (ER)/progesterone receptor(PR) negative or ER and/or PR positive with defects in Fanconi Anemia (FA) pathway repair genes.
II. To determine the safety and tolerability of combining veliparib on a 14-day and 21-day schedule with carboplatin in this patient population.
III. To determine the preliminary efficacy of this combination in this patient population.
SECONDARY OBJECTIVES:
I. To determine the pharmacodynamic endpoints of poly(ADP-ribose) polymerase (PARP) inhibition in the tumor by using, A) 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) of the target lesions, B) circulating tumor cells to detect the induction of the histone variant gamma H2AX, and C) peripheral blood mononuclear cells to assess poly ADP-Ribose (PAR) levels.
II. To determine biomarkers in the primary tumor that may predict antitumor responses to PARP inhibition such as breast cancer 1/2, early onset (BRCA)1/2 protein, Fanconi anemia, complementation group D2 (FANCD2) nuclear foci formation and expression of micro-ribonucleic acid (RNA) 155 (miR 155).
OUTLINE: This is a dose-escalation study of veliparib.
Patients receive carboplatin intravenously (IV) over 1 hour on day 1 and veliparib orally (PO) twice daily (BID) on days 1-7 or 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 1
Kontakter och platser
Studieorter
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-
New York
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Bronx, New York, Förenta staterna, 10461
- Montefiore Medical Center-Einstein Campus
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Bronx, New York, Förenta staterna, 10467
- Montefiore Medical Center - Moses Campus
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Ohio
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Columbus, Ohio, Förenta staterna, 43210
- Ohio State University Comprehensive Cancer Center
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-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
Patients must have histologically or cytologically proven metastatic or locally advanced inoperable breast cancer that fulfills one of the following two criteria:
- Triple-negative breast cancer
- ER and/or PR positive, HER2 negative if their tumors have been shown to be deficient for the FA pathway, based on FA triple stain immunofluorescence (FATSI) screening
HER negative with a known germline BRCA1/2 mutation
- Patients with ER- and/or PR-positive breast cancer will be consented to have their existing, or to be obtained, paraffin-embedded tumor tissue screened for FA deficiency
- No more than 3 prior chemotherapy regimens for metastatic disease will be allowed; any number of prior hormone therapies will be allowed; however, at least 4 weeks should have elapsed since prior chemotherapy (6 weeks for mitomycin C and nitrosoureas and 2 weeks for hormone therapy) or radiation therapy (2 weeks for limited field palliative radiation to the bone)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Patients with treated brain metastases and life expectancy of greater than 3 months
- Patients with known Gilbert syndrome with abnormal unconjugated bilirubin will be eligible
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic acid transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- No prior therapy with veliparib for metastatic disease will be allowed
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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
- Ability to understand and the willingness to sign a written informed consent document
- Patients must be able to swallow pills
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in study
- 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 would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with veliparib
- Known human immunodeficiency virus (HIV)-infected patients on protease inhibitors are ineligible; HIV-infected patients with adequate cluster of differentiation (CD)4 counts (> 500) and not on protease inhibitors are eligible
- Patients with active seizure or a history of seizures are not eligible
- Patients with uncontrolled central nervous system (CNS) metastasis are not eligible; patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Experimentell: Treatment (veliparib, F 18 fluorothymidine, carboplatin)
Patients receive carboplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-7 or 1-14.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients may undergo fluorothymidine PET scan and peripheral blood cell and tumor tissue collection periodically for correlative studies.
|
Korrelativa studier
Givet IV
Andra namn:
Korrelativa studier
Givet PO
Andra namn:
Korrelativa studier
Andra namn:
Korrelativa studier
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Incidence of adverse events to measure the safety and tolerability of this treatment combination
Tidsram: Up to 12 weeks post-treatment
|
Number and severity of toxicity incidents will be tabulated.
Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 standard toxicity grading.
Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE standard toxicity grading.
Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
|
Up to 12 weeks post-treatment
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Clinical response (complete and partial response as well as stable and progressive disease)
Tidsram: Up to 12 weeks post-treatment
|
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline (version 1.1).
|
Up to 12 weeks post-treatment
|
Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
PARP-1 activity
Tidsram: Up to 5 years
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
|
Up to 5 years
|
Thymidine kinase uptake on 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography (FLT-PET) scans
Tidsram: Up to 18 weeks (after course 3)
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
|
Up to 18 weeks (after course 3)
|
Circulating tumor cell markers
Tidsram: Up to 5 years
|
Analysis will be descriptive and exploratory in nature.
Potential relationships and differences will be explored using graphical analyses and quantitative summaries of this marker.
|
Up to 5 years
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Hudsjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Neoplasmer efter plats
- Neoplasmer, körtel och epitel
- Bröstsjukdomar
- Bröstneoplasmer
- Carcinom
- Molekylära mekanismer för farmakologisk verkan
- Anti-infektionsmedel
- Antivirala medel
- Enzyminhibitorer
- Antineoplastiska medel
- Poly(ADP-ribos) polymerashämmare
- Karboplatin
- Veliparib
- Alovudine
Andra studie-ID-nummer
- NCI-2011-02552 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (U.S.S. NIH-anslag/kontrakt)
- UM1CA186712 (U.S.S. NIH-anslag/kontrakt)
- U01CA076576 (U.S.S. NIH-anslag/kontrakt)
- 8609 (Annan identifierare: CTEP)
- CDR0000688990
- OSU 10080
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