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| Name | Class |
|---|---|
| Eisai Inc. | INDUSTRY |
| Schering-Plough | INDUSTRY |
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The combination of TMZ and DAC may effect dual modulation of DNA repair genes resulting in improved clinical response.
Primary Objectives:
Secondary Objectives:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug | In Part I patients will be treated on a standard "3+3" phase I dose-escalation design starting at 0.075 mg/kg until a decitabine dose level of 0.15 mg/kg is reached, or, in case unacceptable toxicities are observed, at the maximum tolerated dose (Phase II recommended dose). Decitabine will be administered at the specified dose level, intravenously, daily 5 days a week for the first 2 weeks of a 6-week cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT) | Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects. | Up to 26 months |
| Overall Response Rate (ORR) | Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. | Up to 30 months |
| Recommended Phase 2 Dose (RP2D) of DAC + TMZ | Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done. | Up to 26 months |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate (DCR) | Using RECIST v1.0 criteria, disease control rate (DCR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD). Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hussein Tawbi, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Cancer Centers | Pittsburgh | Pennsylvania | 15232 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | DAC (Decitabine) 0.075 mg/kg + TMZ (Temozolomide) | Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.075 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2-5 of a 6-week cycle. |
| FG001 | DAC (Decitabine) 0.15 mg/kg + TMZ (Temozolomide) | Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2-5 of a 6-week cycle. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 RP2D DAC + TMZ |
|
| ||||||||||||||||||
| Phase 2 DAC (0.15 mg/kg) + TMZ |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants DAC (Decitabine) + TMZ (Temozolomide) | Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy, or, have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks + TMZ orally 75 mg/m^2 qd for weeks 2-5 of a 6-week cycle). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants That Experienced a Dose Limiting Toxicity (DLT) | Dose-limiting toxicities (DLTs) were defined as grade 4 neutropenia or thrombocytopenia which lasts >7 days; grade 3 or 4 febrile neutropenia; grade 3 or greater non-hematological toxic effects. | Patients participating in the Phase 1 portion of the study that were treated on a standard "3+3" phase I dose-escalation design who were observed for unacceptable toxicities. | Posted | Number | percentage of participants | Up to 26 months |
|
Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DAC (Decitabine) + TMZ (Temozolomide) | Comprehensive listing of adverse events are presented in total (includes events from both Phase 1 and and Phase 2 of study). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hussein Tawbi, MD, PhD | University of Pittsburgh | 713-792-6111 | HTawbi@mdanderson.org |
Not provided
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D009362 | Neoplasm Metastasis |
| D012878 | Skin Neoplasms |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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Not provided
| ID | Term |
|---|---|
| D000077209 | Decitabine |
| D003606 | Dacarbazine |
| D000077204 | Temozolomide |
| D001706 | Biopsy |
| D001707 | Biopsy, Needle |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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|
|
| Temozolomide | Drug | Temozolomide is available in 25 mg and 100 mg tablets that will be administered orally; doses will be rounded to the nearest 25 mg. Temozolomide will be administered orally at 75 mg/m2 daily for 4 weeks starting on week 2 of a 6-week cycle. |
|
|
| biopsy | Procedure | Fine needle aspirates (FNA) and/or core biopsies of tumor samples will be obtained from consenting patients with accessible, evaluable disease, on days 1, 8, 15, and 29 of the first cycle and when patients go off study. Biopsies are optional in Phase I and required for all consenting subjects in Phase II. |
|
|
| Up to 30 months |
| Progression-free Survival (PFS) | PFS was defined as the time from study entry until the documented radiological or symptomatic progression. Per RECIST v1.0 criteria (assessed by MRI or CT): Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions. | Up to 42 months |
| 6-month Progression-free Survival (PFS) Rate | 6 months |
| Overall Survival (OS) | OS was defined as the time from study entry until the death or date of last contract. | Up to 42 months |
| 1-year Overall Survival (OS) Rate | Percentage of patients alive at one year (number of patients alive / total number of evaluable (analyzed) patients). | 12 months |
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Dose Level 2:DAC (Decitabine) 0.15 mg/kg + TMZ (Temozolomide) | Patients with non-resectable stage IIIB/C or stage IV metastatic melanoma with either no prior therapy or have progressed despite prior therapies, who were treated with DAC 0.15 mg/kg intravenously daily × 5 days/week for 2 weeks, TMZ orally 75 mg/m^2 qd for weeks 2-5 of a 6-week cycle. |
|
|
| Primary | Overall Response Rate (ORR) | Using RECIST v1.0 criteria, overall response rate (ORR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD), multiplied by 100. Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. | Posted | Number | percentage of participants | Up to 30 months |
|
|
|
| Primary | Recommended Phase 2 Dose (RP2D) of DAC + TMZ | Toxicity assessments used CTCAE v3.0. Two dose levels were explored in the phase I portion of the study. A modified 3 + 3 'up and down' design was used. Given the knowledge that DAC exhibits its epigenetic effects at 30-fold lower doses than at its maximum-tolerated dose (MTD), escalation of DAC to the MTD was not done. | Posted | Number | mg/kg DAC | Up to 26 months |
|
|
|
| Secondary | Disease Control Rate (DCR) | Using RECIST v1.0 criteria, disease control rate (DCR) was determined by the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) / the number of participants with complete response (CR) + the number of participants with partial response (PR) + the number of participants with stable disease (SD) + the number of participants with progressive disease (PD). Per RECIST v1.0 criteria (assessed by MRI or CT): Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response (PR) nor sufficient increase to to qualify for Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. | Posted | Number | percentage of participants | Up to 30 months |
|
|
|
| Secondary | Progression-free Survival (PFS) | PFS was defined as the time from study entry until the documented radiological or symptomatic progression. Per RECIST v1.0 criteria (assessed by MRI or CT): Progressive Disease (PD); PD, 20% increase in the sum if target lesion or the appearance of new lesions. | Posted | Median | Full Range | months | Up to 42 months |
|
|
|
| Secondary | 6-month Progression-free Survival (PFS) Rate | Patients that either progressed or died by 6 months. | Posted | Number | percentage of participants | 6 months |
|
|
|
| Secondary | Overall Survival (OS) | OS was defined as the time from study entry until the death or date of last contract. | Posted | Median | 95% Confidence Interval | months | Up to 42 months |
|
|
|
| Secondary | 1-year Overall Survival (OS) Rate | Percentage of patients alive at one year (number of patients alive / total number of evaluable (analyzed) patients). | Posted | Number | percentage of participants | 12 months |
|
|
|
| 7 |
| 39 |
| 39 |
| 39 |
| Febrile neutropenia | Infections and infestations | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Neuropathy: motor | Nervous system disorders | Systematic Assessment |
|
| Pain, Abdomen NOS | General disorders | Systematic Assessment |
|
| Pain, Back | General disorders | Systematic Assessment |
|
| Peripheral arterial ischemia | Vascular disorders | Systematic Assessment |
|
| Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) | Immune system disorders | Systematic Assessment |
|
| Anorexia | General disorders | Systematic Assessment |
|
| Confusion | Nervous system disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Edema: limb | Blood and lymphatic system disorders | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | Systematic Assessment |
|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | Systematic Assessment |
|
| Heartburn/dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hemorrhage/Bleeding - Other (Specify, __) | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypertension | Cardiac disorders | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, Skin (cellulitis) | Infections and infestations | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS | Infections and infestations | Systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
|
| Leukocytes (total WBC) | Blood and lymphatic system disorders | Systematic Assessment |
|
| Metabolic/Laboratory - Other (Specify, __) | Metabolism and nutrition disorders | Systematic Assessment |
|
| Mood alteration, Anxiety | Nervous system disorders | Systematic Assessment |
|
| Mood alteration, Depression | Nervous system disorders | Systematic Assessment |
|
| Mucositis/stomatitis (clinical exam), Oral cavity | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | Systematic Assessment |
|
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pain, Abdomen NOS | General disorders | Systematic Assessment |
|
| Pain, Back | General disorders | Systematic Assessment |
|
| Pain, Chest wall | General disorders | Systematic Assessment |
|
| Pain, Extremity-limb | General disorders | Systematic Assessment |
|
| Pain, Head/headache | General disorders | Systematic Assessment |
|
| Pain, Joint | General disorders | Systematic Assessment |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pruritus/itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Taste alteration (dysgeusia) | Gastrointestinal disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Weight loss | General disorders | Systematic Assessment |
|
Not provided
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| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D011677 | Punctures |