- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT01263145
MK2206 and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors or Metastatic Breast Cancer
Phase Ib Dose Escalation and Biomarker Study of MK-2206 in Combination With Standard Doses of Weekly Paclitaxel in Patients With Locally Advanced or Metastatic Solid Tumors With an Expansion in Advanced Breast Cancer
Přehled studie
Postavení
Detailní popis
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of the combination of MK-2206 and weekly paclitaxel. (Dose-escalation phase) II. To determine the safety and anti-tumor activity of the combination in metastatic breast cancer. (Expansion phase)
SECONDARY OBJECTIVES:
I. To determine the pharmacokinetics of MK-2206 and weekly paclitaxel used in combination.
II. To determine the safety of MK-2206 and weekly paclitaxel used in combination.
III. To evaluate the toxicities and tolerability of the combination. IV. To document anti-tumor activity. V. To determine baseline molecular markers that may predict clinical activity. VI. To determine pharmacodynamic markers in blood and tumor tissue that may predict an increase in apoptosis (by cleaved caspase 3) and clinical activity.
VII. To determine concordance of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and phosphatase and tensin homolog (PTEN) status between primary tumor and distant metastasis.
VIII. To determine concordance of PIK3CA status of circulating tumor cells and distant metastasis.
OUTLINE: This is a dose-escalation study of Akt inhibitor MK2206.
Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 orally (PO) once daily (QD) on days 2, 9, and 16. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 weeks.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02215
- Dana-Farber Cancer Institute
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Tennessee
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Nashville, Tennessee, Spojené státy, 37232
- Vanderbilt University/Ingram Cancer Center
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Texas
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Houston, Texas, Spojené státy, 77030
- M D Anderson Cancer Center
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have received at least two lines of therapy; for the expansion phase: female patients with metastatic breast cancer who have received a maximum of three lines of therapy
- Absolute neutrophil count (ANC) >= 1,000/uL
- Platelets >= 100,000/uL
- Hemoglobin (Hgb) >= 9 g/dL
- Creatinine =< 1.5 x upper limit of normal (ULN)
- Prothrombin time (PT) within institutional guideline for biopsy procedure
- Total bilirubin =< 1.5 x ULN
- Alanine aminotransferase (ALT) =< 2.5 x ULN (=< 3 x ULN for subjects with liver involvement with cancer)
- A known diabetic patient who is taking insulin or oral anti-diabetic therapy must have a hemoglobin A1C (HBA1C) =< 8% or a fasting serum glucose =< 110% ULN
- Patient will have a tumor suitable for fine-needle aspirates (FNA) and core biopsy for research purposes (determined by the treating physician)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or evaluable disease (e.g., bone metastasis or lesions which do not fulfill RECIST criteria for metastatic disease)
Patients with central nervous system (CNS) metastasis who have completed a course of therapy (for treatment of CNS metastasis) would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as:
- No evidence of new or enlarging CNS metastasis
- Off steroids and anticonvulsants
- Corrected QT (QTc) interval =< 450 msec (Bazett's formula)
- Negative serum pregnancy test beta-human chorionic gonadotropin (hCG) for patients of childbearing age
- For the dose escalation cohorts, patients must have received front-line, cytotoxic, systemic therapy (combination or single agent, with or without the addition of targeted agents) for advanced cancer
- For the expansion cohort, patients must have received no more than three lines of cytotoxic systemic therapy (combination or single agent, with or without the addition of targeted agents) for metastatic breast cancer; patients could have received paclitaxel in the adjuvant setting, but not in the metastatic setting
- The last line of therapy must have been administered > 21 days prior to initiation of treatment on this study
- Women of childbearing potential and men must use two forms of 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 she or her partner is participating in this study, the patient should inform the treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Both men and women and members of all races and ethnic groups are eligible for this trial
Exclusion Criteria:
- Patients may not be receiving any other investigational agents
- Patients taking a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitor or inducer will be excluded; patients who have discontinued any of these medications must have a wash-out period of at least 5 days or at least 5 half-lives of the drug (whichever is longer) prior to the first dose MK-2206
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or other agents used in the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bradycardia, related to cardiac disease, bundle branch block, 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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
---|---|
Experimentální: Treatment (Akt inhibitor MK2206 and paclitaxel)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and Akt inhibitor MK2206 PO QD on days 2, 9, and 16.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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Korelační studie
Korelační studie
Vzhledem k tomu, IV
Vzhledem k PO
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
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Antitumor activity of the combination in metastatic breast cancer (Expansion phase)
Časové okno: Up to 3 weeks after completion of study treatment
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Up to 3 weeks after completion of study treatment
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MTD of the combination of MK-2206 and paclitaxel defined as the dose level in which less than or equal to 1 out of 6 patients develop dose limiting toxicity assessed using Common Terminology Criteria for Adverse Events version 4 (Phase I)
Časové okno: 21 days
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21 days
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Change in average number of circulating tumor cells (CTCs)
Časové okno: Baseline to up to 2 weeks
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Will be determined by chi-square analysis or Fisher's Exact test and compared by Student t-test.
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Baseline to up to 2 weeks
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Change in multiplex proteomics
Časové okno: Baseline to up to day 17
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Baseline to up to day 17
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Change in percentage of biomarkers assessed using immunohistochemistry
Časové okno: Baseline to up to 2 weeks
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Baseline to up to 2 weeks
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Change in percentage of marker of proliferation Ki-67 (Ki-67) positive cells
Časové okno: Baseline to up to 2 weeks
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Will be calculated using a two-sided one-sample t-test, at a significance level of 0.05.
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Baseline to up to 2 weeks
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Change in reverse phase proteomic arrays (RPPA)
Časové okno: Baseline to up to day 8
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Will be analyzed using the Wilcoxon rank test.
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Baseline to up to day 8
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Pharmacokinetic parameters of Akt inhibitor MK2206
Časové okno: On days 1-3, 5, 8, 16, 17, and 19 of course 1 and then on day 1 of all subsequent courses
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Standard analyses for the pharmacokinetic endpoints will be conducted, including summary of descriptive measures, e.g., tabulation of frequencies for categorical variables, numerical (mean, range, standard deviation, 95% confidence intervals) and graphical (box plots, histograms) summary of the distribution for continuous endpoints, correlation analyses (Pearson and Spearman), and linear and nonlinear regression analyses, etc.
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On days 1-3, 5, 8, 16, 17, and 19 of course 1 and then on day 1 of all subsequent courses
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Pharmacokinetic parameters of paclitaxel
Časové okno: On days 1, 2, 15, and 16 of course 1
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Standard analyses for the pharmacokinetic endpoints will be conducted, including summary of descriptive measures, e.g., tabulation of frequencies for categorical variables, numerical (mean, range, standard deviation, 95% confidence intervals) and graphical (box plots, histograms) summary of the distribution for continuous endpoints, correlation analyses (Pearson and Spearman), and linear and nonlinear regression analyses, etc.
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On days 1, 2, 15, and 16 of course 1
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Change in expression of plasma markers
Časové okno: Baseline to up to day 17
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The marker expression will be compared by Student t-test.
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Baseline to up to day 17
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PIK3CA mutation status
Časové okno: Up to day 17
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Chi-square or Fisher's exact status will be used to calculate associations between PIK3CA status and clinical parameters.
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Up to day 17
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Prevalence of single nucleotide polymorphisms (SNPs) in PI3K pathway genes
Časové okno: Up to day 17
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Descriptive analysis will be performed.
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Up to day 17
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
- NCI-2011-02562 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- P30CA016672 (Grant/smlouva NIH USA)
- U01CA062490 (Grant/smlouva NIH USA)
- U01CA062461 (Grant/smlouva NIH USA)
- 8739 (Jiný identifikátor: CTEP)
- 2010-0245 (Jiný identifikátor: M D Anderson Cancer Center)
- CDR0000690723
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