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A Trial In Patients With Advanced Cancer And Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00878189
Recruitment Status : Completed
First Posted : April 8, 2009
Results First Posted : November 12, 2019
Last Update Posted : November 12, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a phase 1, dose escalating study to determine the safety of PF-03084014 in patients with advanced cancer and leukemia

Condition or disease Intervention/treatment Phase
Neoplasms by Histologic Type Drug: PF-03084014 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE I TRIAL OF PF-03084014 IN PATIENTS WITH ADVANCED SOLID TUMOR MALIGNANCY AND T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA
Actual Study Start Date : June 25, 2009
Actual Primary Completion Date : January 10, 2013
Actual Study Completion Date : November 22, 2016


Arm Intervention/treatment
Experimental: 1 Drug: PF-03084014
10 mg, 50 mg or 100 mg tablets. Patients dosed from 20 mg - 500 mg, twice daily
Other Name: gamma secretase inhibitor




Primary Outcome Measures :
  1. Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT) [ Time Frame: Baseline to the end of Cycle 1 (Week 4) ]
    Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities >= Grade 3 despite optimal care; treatment delay >=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia >7 days; febrile neutropenia; neutropenic infection; Grade >=3 thrombocytopenia with bleeding

  2. Number of T-ALL/LBL Participants With First-Cycle DLT [ Time Frame: Baseline to the end of Cycle 1 (Week 4) ]
    Any DLT attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities >= Grade 3 despite optimal care; treatment delay >=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) <1000/microliter (uL), or platelet count <30,000/uL, or hemoglobin <8 gram/deciliter (g/dL) in a bone marrow with <5% blasts and no evidence of leukemia or abnormal dysplasia for >42 days


Secondary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of casual relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.

  2. Number of Participants With TEAEs (Treatment-Related) [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.

  3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) by Severity (by Maximum Common Terminology Criteria for Adverse Events [CTCAE] Grade) [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.

  4. Number of Participants With TEAEs (Treatment-Related) by Severity (by Maximum CTCAE Grade) [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.

  5. Number of Participants With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    Criteria for potentially important changes in ECG were defined as: maximum (max.) post-dose (post-baseline) time from electrocardiogram Q wave to the corresponding to electrical systole (QT interval) corrected for Fridericia's factor (QTcF), or QT interval corrected for Bazett's factor (QTcB): <450, 450 -<480, 480-<500, and >=500 msec. Maximum increase (inc.) from baseline in QTcF or QTcB: change (chg) <30, 30>=chg<60, and chg >=60 msec.

  6. Number of Participants With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles) [ Time Frame: Baseline up to end of study (maximum of 84 months) ]
    Parameters analyzed included: white blood cell (WBC) count plus differential, absolute (abs) neutrophil count, platelets, hemoglobin, sodium, potassium, bicarbonate, chloride, blood urea nitrogen, creatinine, glucose, uric acid, calcium, phosphate, magnesium, total protein, albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), partial prothrombin time/international normalized ratio (PTT/INR). Urinalysis: pH, specific gravity, protein, glucose, ketones, blood, leukocyte esterase, and nitrites. Pregnancy test: Serum or urine pregnancy test for women of childbearing potential. There were no changes in urine protein among the solid tumor and T-ALL/LBL participants that were clinically significant. Clinical significance was judged by the investigator.

  7. Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) ]
    Cmax was the maximum observed serum concentration.

  8. Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) ]
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

  9. Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) ]
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). CV is the coefficient of variation.

  10. Dose-normalized AUCtau [AUCtau (dn) ] After a Single Dose on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) ]
    AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. NE is not estimable.

  11. Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose) ]
    Tmax was the time to reach maximum serum concentration (Cmax).

  12. Cmax After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Cmax was the maximum observed serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant. CV is the coefficient of variation.

  13. Time to Reach Cmax (Tmax) After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Tmax was the time to reach maximum serum concentration (Cmax). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  14. AUCtau After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  15. Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  16. Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Serum decay half-life (t1/2) is the time measured for the serum concentration to decrease by one half. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  17. Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  18. Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Cmin was the minimum serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  19. Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Cavg was the average serum concentration at steady state. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  20. Accumulation Ratio (Rac) on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose), Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Accumulation was calculated as AUCtau at steady state (Cycle 1 Day 21) divided by AUCtau after a single dose on Cycle 1 Day 1. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  21. Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  22. Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) ]
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

  23. AUCtau in the Fasted State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).

  24. AUCtau in the Fed State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).

  25. Cmax in the Fasted State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Cmax was the maximum observed serum concentration.

  26. Cmax in the Fed State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Cmax was the maximum observed serum concentration.

  27. Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.

  28. Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.

  29. Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

  30. Dose-Normalized Cmax [Cmax(dn)] in the Fed State for Solid Tumor Participants [ Time Frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose). ]
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

  31. AUCtau on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Data for this outcome measure was planned to be analyzed for two arms only.

  32. Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.

  33. Cmax on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Cmax was the maximum observed serum concentration. Data for this outcome measure was planned to be analyzed for two arms only.

  34. Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.

  35. Tmax on Cycle 2 Day 1 [ Time Frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) ]
    Tmax was the time to reach maximum serum concentration (Cmax). Data for this outcome measure was planned to be analyzed for two arms only.

  36. Percentage of Solid Tumor Participants With Objective Response (OR) [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (plus [+] or minus [-] 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles ]
    Objective response (OR) was defined as confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as >=30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.

  37. Time to Tumor Progression (TTP) for Solid Tumor Participants [ Time Frame: Baseline until first documented objective progression (up to maximum of 84 months) ]
    Time from Cycle 1 Day 1 to first documentation of disease progression. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, uneuivocal progression of non-target disease, or the appearance of new lesions. TTP (months) was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.

  38. Duration of Response (DR) for Solid Tumor Participants [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months) ]
    Time from the first documentation of OR to objective disease progression or death due to any cause. DR was only calculated for participants with an OR. DR (months) was calculated as (date of first documentation of objective progression or death minus date of first documentation of PR or CR plus 1) divided by 30.

  39. Progression-Free Survival (PFS) for Solid Tumor Participants [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months) ]
    PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of progression or death due to any cause. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions. PFS (months) was calculated as (the first event date minus the date of first dose of study medication plus 1) divided by 30.

  40. Percentage of T-ALL/LBL Participants With OR [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) ]
    OR was adapted from International Working Group Response Criteria for Acute Myeloid Leukemia (AML). The response categories of interest were CR, complete response with incomplete hematopoietic recovery (CRi), and PR. CR: ANC >1500/microliter (uL), no circulating blasts. Platelets >100,000/uL, <5% marrow blast cells, no extramedullary disease, bone marrow cellularity >20% with tri-lineage hematopoiesis and <5% marrow blast cells, none of which were neoplastic; CRi: same as CR but ANC may be >1500/uL or platelet count >100,000/uL, no requirement on bone marrow cellularity; PR: same as CR but bone marrow with >= 50% reduction of leukemia blast cells and an absolute blast count between 5% and 25%.

  41. Relapse Free Survival (RFS) for T-ALL/LBL Participants [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) ]
    The RFS of CR was defined as the time from the date of first attaining CR to the date of relapse or death from any cause, whichever occurred first. Similarly, the RFS of CR + CRi (or RFS of CR + CRi + PR) was defined as the time from the date of first attaining CR + CRi (or CR + CRi + PR) to the date of relapse or death from any cause, whichever occurred first.

  42. Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Participants [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months) ]
    PBR was the maximum percentage of peripheral blast count reduction for each participant who received at least one dose of study medication. PBR was derived by the Sponsor from percentage of peripheral blood Blast Count reported by sites.

  43. Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Participants: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline [ Time Frame: Baseline, Cycle 1 Day 21 (-5 days) ]
    Gene expression analysis in tumor biopsies was done using cDNA prepared from RNA extracted from tumor biopsies. Gene expression was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Only Hes4 gene showed consistent down modulation across dosing cohorts (150 mg and 220 mg BID) and therefore results were reported for Hes4 only. Data for this outcome measure was planned to be analyzed for two arms only.

  44. Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Participants: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline [ Time Frame: Baseline (morning), Cycle 1 Days 8, 15 and 21 (morning, matched with the first PK sample of the particular day), Cycle 1 Day 21 (24, 48, and 120 hr post-dose) and at end of treatment (EOT) ]
    Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).

  45. Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Participants: Hes4 Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline [ Time Frame: Baseline (morning), Cycle 1 Days 8 and 21 (pre-dose) ]
    Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).

  46. Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Participants [ Time Frame: Baseline, Cycle 1 Days 8 and 15 (pre-dose AM), Cycle 1 Day 21 (pre-dose AM and 24, 48 and 120 hr post-dose) and end of treatment (EOT). ]
    Notch intracellular domain (NICD) levels was measured in peripheral blood mononuclear cell (PBMC) pellets using a validated enzyme-linked immunosorbent assay (ELISA).

  47. Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Participants [ Time Frame: Baseline, Cycle 1 Day 1 and Cycle 2 Day 1 ]
    Notch intracellular domain (NICD) was to be measured in bone marrow monoculear cell (BMMC) cell pellets using a validated ELISA.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with advanced cancer that is resistant to standard therapy or for which no standard therapy is available
  • Patients with acute T cell leukemia/lymphoblastic lymphoma that is resistant to standard therapy or for which no standard therapy is available
  • Men and women >16 years old

Exclusion Criteria:

  • Prior treatment with a gamma secretase inhibitor for treatment of cancer
  • Patients taking Tamoxifen
  • Patients with active graft versus host disease
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  • Patients who are pregnant or breast feeding
  • Patients with clinical evidence of central nervous system disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00878189


Locations
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United States, Colorado
Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
University of Colorado Denver CTRC
Aurora, Colorado, United States, 80045
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Clinical Laboratory
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana Ferber Cancer institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Center / Wayne State University
Detroit, Michigan, United States, 48201
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Italy
DIPRTMNT CLIN Scienze RADIOL e Istocitopatologiche
Bologna, Italy, 40138
Istituto di Ematologia Seragnoli
Bologna, Italy, 40138
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00878189    
Other Study ID Numbers: A8641014
2010-022036-36 ( EudraCT Number )
First Posted: April 8, 2009    Key Record Dates
Results First Posted: November 12, 2019
Last Update Posted: November 12, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Keywords provided by Pfizer:
Phase 1 dose escalation study in advanced solid tumor malignancy and leukemia
Additional relevant MeSH terms:
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Leukemia
Neoplasms by Histologic Type
Neoplasms