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For the last patient still on treated nominal therapeutic use of the Milciclib was approved at INT Milano.
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The intent of the study is to assess the antitumor activity of PHA-848125AC in patients with recurrent or metastatic, unresectable malignant thymoma previously treated with multiple lines of chemotherapy.
This is a single-arm, open-label, multicenter, phase II clinical trial design with an early stopping rules. PHA-848125AC will be administered to patients with recurrent metastatic unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior systemic therapy for advanced / metastatic disease. The intent of the study is to assess the antitumor activity of PHA-848125AC and ultimately to improve the outcome of the patients. The primary end point for this study is a progression free survival rate of 3 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Milciclib | Experimental | Milciclib Maleate capsules |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Milciclib Maleate | Drug | 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle. Number of cycles: until disease progression or unacceptable toxicity. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival Rate at 3 Months | The proportion of successes (i.e. patients alive and progression-free at 3 months since treatment start) out of the total number of evaluable patients. | 3 months since treatment start |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters | The adverse events (AEs) were coded with the Medical Dictionary for Regulatory Activities (MedDRA) and their severity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The following subsets of AEs were considered: serious AEs, AEs with CTCAE grade 3-5, AEs with a relationship to study treatment classified by the Investigator as possible or probable or definite and AEs reported as leading to discontinuation from treatment. Laboratory test values were graded according to the NCI CTCAE scale, v3.0, whenever possible. For each laboratory test included in the NCI CTCAE system, the incidence of abnormalities were evaluated by considering the worst occurrence for each patient throughout the whole treatment period. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arun Rajan, MD. | National Cancer Institute (NCI) | Principal Investigator |
| Marina C. Garassino, MD. | Fondazione IRCCS Istituto Nazionale dei Tumori di Milano | Principal Investigator |
| Giuseppe Giaccone, MD | MedStar Gergetown University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States | ||
Four patients were screening failure.
Subjects were enrolled from 02 Feb 2011 to 28 Jan 2016 by 2 centers in US and one in Italy.
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| ID | Title | Description |
|---|---|---|
| FG000 | Milciclib | Milciclib Maleate capsules Milciclib Maleate: 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle. Number of cycles: until disease progression or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Milciclib | Milciclib Maleate capsules Milciclib Maleate: 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle. Number of cycles: until disease progression or unacceptable toxicity. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Progression-free Survival Rate at 3 Months | The proportion of successes (i.e. patients alive and progression-free at 3 months since treatment start) out of the total number of evaluable patients. | Evaluable patients, i.e., consists of all eligible and treated patients who fulfill the following additional conditions: 1) they receive at least 80% of drug in the first two cycles overall; 2) they have baseline and > or = 1 on-treatment tumor/oncologic assessment(s) or die before tumor re-assessment. | Posted | Count of Participants | Participants | 3 months since treatment start |
|
Adverse events were reported for patients from consent signed to 28 days after last dose of study drug. Individual patient adverse event reporting ranged from 5.1 weeks to 141.3 weeks with a median of 19.28 weeks.
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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 | Milciclib | Milciclib Maleate capsules Milciclib Maleate: 150 mg/day once daily, for 7 consecutive days (days 1 to 7) followed by 7 days of rest (days 8 to 14) in a 2-week cycle. Number of cycles: until disease progression or unacceptable toxicity. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Haemoptisys | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Davite Cristina | CLIOSS S.r.l. | +39 0031 58 | 1482 | regulatory@clioss.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 9, 2017 | May 22, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: CDKO-125a-007_ALG_V1 | Apr 22, 2013 | May 22, 2018 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: CDKO-125a-007_TLG_V1 | Apr 22, 2013 | May 22, 2018 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D013945 | Thymoma |
| ID | Term |
|---|---|
| D018193 | Neoplasms, Complex and Mixed |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D013953 | Thymus Neoplasms |
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| ID | Term |
|---|---|
| C550092 | N,1,4,4-tetramethyl-8-((4-(4-methylpiperazin-1-yl)phenyl)amino)-4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline-3-carboxamide |
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|
| Adverse events: from date treatment consent signed to 28 days after last treatment; hematology/blood chemistry tests: at baseline and between Day 11-14 of each cycle of a maximum total of 48 two-week cycles. |
| Objective Response Rate (ORR) | Point and 95% confidence interval estimates was calculated for the objective tumor response rate (confirmed CRs or PRs). The determination of antitumor efficacy was based on objective tumor assessments made according to the RECIST guideline (version 1.1). The analysis was performed in the evaluable population. | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
| Disease Control Rate (ORR+SD Rate) | Point and 95% confidence interval estimates was calculated for the disease control rate (confirmed CRs / PRs and SD > or = 6 weeks). The analysis was performed in the evaluable patient populations. | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
| Duration of Response | Calculated in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria. | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
| Overall Survival | The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, and to the date in which the patients diagnosed with the disease are still alive. Kaplan-Meier estimates as percentage of patients alive. | Every 6 weeks during Follow-Up until PD or new therapy start; every 6 months thereafter, up to 2 years from the last dose of study drug. |
| Progression-free Survival (PFS) | The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
| NIH, Center for Cancer Research, Medical Oncology |
| Bethesda |
| Maryland |
| 20892 |
| United States |
| Fondazione IRCCS Istituto Nazionale dei Tumori di Milano | Milan | (mi) | 20133 | Italy |
| Sponsor's decision |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| World Health Organization classification (International Classification of Diseases) | Count of Participants | Participants |
|
| Tumor extent at study entry | Count of Participants | Participants |
|
| Masaoka clinical staging at study entry | Staging used to evaluate invasiveness of the tumor. | Count of Participants | Participants |
|
|
|
|
| Secondary | Adverse Events (NCI CTCAE) and Hematological and Blood Chemistry Parameters | The adverse events (AEs) were coded with the Medical Dictionary for Regulatory Activities (MedDRA) and their severity graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The following subsets of AEs were considered: serious AEs, AEs with CTCAE grade 3-5, AEs with a relationship to study treatment classified by the Investigator as possible or probable or definite and AEs reported as leading to discontinuation from treatment. Laboratory test values were graded according to the NCI CTCAE scale, v3.0, whenever possible. For each laboratory test included in the NCI CTCAE system, the incidence of abnormalities were evaluated by considering the worst occurrence for each patient throughout the whole treatment period. | All treated patients | Posted | Count of Participants | Participants | Adverse events: from date treatment consent signed to 28 days after last treatment; hematology/blood chemistry tests: at baseline and between Day 11-14 of each cycle of a maximum total of 48 two-week cycles. |
|
|
|
| Secondary | Objective Response Rate (ORR) | Point and 95% confidence interval estimates was calculated for the objective tumor response rate (confirmed CRs or PRs). The determination of antitumor efficacy was based on objective tumor assessments made according to the RECIST guideline (version 1.1). The analysis was performed in the evaluable population. | Evaluable population: the patient population consists of all eligible and treated patients who fulfill the following additional conditions: 1) they receive at least 80% of drug in the first two cycles overall; 2) they have baseline and > or = 1 on-treatment tumor/oncologic assessment(s) or die before tumor re-assessment. | Posted | Number | 95% Confidence Interval | Percentage of patients | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
|
|
|
| Secondary | Disease Control Rate (ORR+SD Rate) | Point and 95% confidence interval estimates was calculated for the disease control rate (confirmed CRs / PRs and SD > or = 6 weeks). The analysis was performed in the evaluable patient populations. | Evaluable patients | Posted | Number | 95% Confidence Interval | Percentage of patients | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
|
|
|
| Secondary | Duration of Response | Calculated in patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria. | Patients achieving a confirmed objective tumor response by RECIST version 1.1 criteria. | Posted | Number | Months | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
|
|
|
| Secondary | Overall Survival | The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, and to the date in which the patients diagnosed with the disease are still alive. Kaplan-Meier estimates as percentage of patients alive. | Evaluable patients | Posted | Number | percentage of patients dead at 21 months | Every 6 weeks during Follow-Up until PD or new therapy start; every 6 months thereafter, up to 2 years from the last dose of study drug. |
|
|
|
| Secondary | Progression-free Survival (PFS) | The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. | Evaluable patients | Posted | Median | 95% Confidence Interval | Months | Assessments were made every 6 weeks from start date until PD or up to a maximum duration of 134 weeks. |
|
|
|
| 13 |
| 30 |
| 14 |
| 30 |
| 28 |
| 30 |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dyspnoea NOS | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Abdominal pain NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Gastrointestinal obstruction NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pneumonia NOS | Infections and infestations | MedDRA (5.1) | Non-systematic Assessment |
|
| Sepsis NOS | Infections and infestations | MedDRA (5.1) | Non-systematic Assessment |
|
| Extrapyramidal disorder | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Sweating increased | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | MedDRA (5.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Blood alkaline phosphatase NOS increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Epididymitis NOS | Reproductive system and breast disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA (5.1) | Non-systematic Assessment |
|
| Diarrhoea NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Vomiting NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Abdominal pain NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Gastrointestinal disorder NOS | Gastrointestinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pain NOS | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pain exacerbated | General disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Haedache | Nervous system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dyspnoea NOS | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Appetite decreased NOS | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dehydratation | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Blood amylase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (5.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Nail disorder NOS | Skin and subcutaneous tissue disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (5.1) | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Azotaemia | Renal and urinary disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (5.1) | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (5.1) | Non-systematic Assessment |
|
Not provided
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| Title | Measurements |
|---|---|
|