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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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This multicenter, open-label, phase II trial aims to assess the safety and efficacy of palbociclib in adult patients with Oligodendroglioma or recurrent oligoastrocytoma anaplastic with the activity of the protein RB preserved.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Palbociclib (PD0332991) | Experimental | Palbociclib will be administrated orally at a dose of 125 mg/day during 21 days followed by a break of 7 days. All patients included will be treated in the same arm. Treatment will be administrated until disease progression, unacceptable adverse side effects or study end. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Palbociclib | Drug | Palbociclib will be administered orally at a dose of 125 mg/day, until disease progression, unacceptable adverse side effects or study end. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) at Six Months (PFS6m) | Percentage of patients who have progressed / no progress after 6 months of treatment | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability of Oral Administration of PD0332991 (Reported Adverse Events, Physical Examinations and Laboratory Tests. Toxicity Will be Classified and Tabulated by NCI-CTCAE v 4.0.) | Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0. |
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Inclusion Criteria:
Ability to understand and sign the informed consent approved by the Ethic Committee.
Men or women aged greater than or equal to 18.
Patients with oligodendroglioma anaplastic or oligoastrocytoma anaplastic according to WHO classification and histologically confirmed. Note: It can be included patients with oligoastrocytoma or oligodendroglioma G2 only if they have suffered a recurrence in which the diagnosis of the resection were G3.
Patients in relapse after radiotherapy and one or two lines of chemotherapy. Note: Both previous radiotherapy and chemotherapy could be received in adjuvant therapy or previous recurrences. It is also accepted to be received concurrent chemoradiotherapy. In the secondary oligodendrogliomas or oligoastrocytomas anaplastic, the patients could have received chemotherapy and radiotherapy when the tumor was G2.
All patients have to present positivity in immunohistochemical study for the RB protein in the tumor samples sent to the central lab.
The cases must have 10 slides or a tumor block available from a biopsy or surgery.
All patients have to show disease progression in a cerebral nuclear magnetic resonance.
Interval of at least one week between the previous intracranial biopsy and the inclusion.
Interval of at least 12 weeks between radiotherapy and the inclusion, unless: a) Recurrent tumor confirmed histologically b) recurrency showed in the NMR out of radiotherapy.
Patients should have been recovered from previous therapies: 28 days since the end of any investigational product and since the end of any cytotoxic treatment.
ECOG≤2
Stable or decreasing dose of corticoids during the five days prior to the inclusion
patients who have been suffered from a tumor resection in the last recurrence are eligible if:
Good bone marrow function:
Nor pregnant women nor breast-feeding women. Women with heterosexual activity should have a negative pregnant test before the inclusion in the study. Both women and men should use an accepted contraceptive method during the study treatment and 1 month after treatment completed.
Exclusion Criteria:
Presence of meningeal carcinomatosis disseminated.
Concomitant treatment with other investigational products
Previous treatment wih an investigational product that could be active for CDK4/6
Any kind of surgery in the previous 2 weeks
Presence of any clinically significant gastrointestinal abnormality that can affect oral administration, transit or absorption of study drug, such as the inability to take medication by mouth as tablets.
Presence of any psychiatric or cognitive disorder that limits the understanding or the signature of informed consent and / or jeopardize the fulfillment of the requirements of this protocol.
In the 7 days prior to the beginning of the treatment, to have received a treatment with: - Drugs inhibitor of the CYP3A4 - Drugs inductors of the CYP3A4 - Drugs that extends the QT interval
QTc interval >480 msec, familiar history or personal of QT large Syndrome, QT short Syndrome, Brugada syndrome, QTc extension or Torsade de Pointes history
Electrolyte disorder that may affect the QTc interval
Significant or uncontrolled cardiovascular disease, including:
History of any cancer, except for the following circumstances:
Patients positive for HIV
Inflammatory bowel disease, chronic diarrhea, short gut syndrome or any upper gastrointestinal surgery including gastric resection.
History of allergic reactions to Palbociclib
Another acute or chronic serious medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of test results and that,investigator's discretion, make the patient inappropriate for entry into this trial. Uncontrolled intercurrent illness including, but are not limited to, ongoing or active infection or psychiatric illness / social situations that limit the compliance of study requirements.
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| Name | Affiliation | Role |
|---|---|---|
| Juan Manuel Sepúlveda | H. 12 de Octubre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Insular de Canarias | Las Palmas de Gran Canaria | Las Palmas | Spain | |||
| Hospital Son Espases |
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A total of 79 patients were screened and eventually 34 patients fulfilled all the inclusion and exclusion criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Palbociclib (PD0332991) | Palbociclib will be administrated orally at a dose of 125 mg/day during 21 days followed by a break of 7 days. All patients included will be treated in the same arm. Treatment will be administrated until disease progression, unacceptable adverse side effects or study end. Palbociclib: Palbociclib will be administered orally at a dose of 125 mg/day, until disease progression, unacceptable adverse side effects or study end. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Jul 1, 2019 | Nov 22, 2023 |
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|
| Three years |
| Anti-tumor Response According to RANO Criteria | According to RANO criteria, assessed by the PI of each center. There will be a central review. | 30 months |
| Overall Survival (OS) | Time from randomization to death by any cause. | With a median follow-up of 12 (0.9-52.2) months |
| Changes in the Use of Glucocorticoids | Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution | 30 months |
| Palma de Mallorca |
| Mallorca |
| Spain |
| Consorcio Hospitalario Provincial de Castellón | Castellon | Valencia | Spain |
| Hospital Clínic de Barcelona | Barcelona | Spain |
| ICO Hospitalet | Barcelona | Spain |
| Hospital de León | León | Spain |
| Hospital 12 de Octubre | Madrid | Spain |
| Hospital Ramón y Cajal | Madrid | Spain |
| Hospital Regional de Málaga | Málaga | Spain |
| Hospital Virgen del Rocio | Seville | Spain |
| Hospital Universitario y Politécnico La Fe | Valencia | Spain |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | All patients included in the study received treatment with the experimental drug, Palbociclib, at a dose of 125 mg/day on days 1-21 in 28-day cycles. The IMP was administered for 21 days followed by 7 days off. Treatment cycles continued until there was unacceptable toxicity, tumor progression, withdrawal of consent or death. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| ECOG, Categorical | The ECOG-PS scale describes a patient's level of functioning in terms of their ability to care for them selves, and carry activities of daily living. The scale values are: 0: Fully active, without restriction
| Count of Participants | Participants |
| ||||||||||||||||||||||
| Prior treatment Temozolomide | Count of Participants | Participants |
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| 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 (PFS) at Six Months (PFS6m) | Percentage of patients who have progressed / no progress after 6 months of treatment | Posted | Number | 95% Confidence Interval | Percentage of participants | 6 months |
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| ||||||||||||||||||||||||||
| Secondary | Safety and Tolerability of Oral Administration of PD0332991 (Reported Adverse Events, Physical Examinations and Laboratory Tests. Toxicity Will be Classified and Tabulated by NCI-CTCAE v 4.0.) | Type, incidence, severity, frequency, severity and relationship with IMP of reported adverse events, physical examinations and laboratory tests. Toxicity will be classified and tabulated by NCI-CTCAE v 4.0. | Palbociclib will be administrated orally at a dose of 125 mg/day during 21 days followed by a break of 7 days. All patients included will be treated in the same arm. Treatment will be administrated until disease progression, unacceptable adverse side effects or study end. Palbociclib: Palbociclib will be administered orally at a dose of 125 mg/day, until disease progression, unacceptable adverse side effects or study end. | Posted | Count of Participants | Participants | Three years |
|
| |||||||||||||||||||||||||||
| Secondary | Anti-tumor Response According to RANO Criteria | According to RANO criteria, assessed by the PI of each center. There will be a central review. | Patients with recurrent anaplastic (Grade III) oligodendrogliomas | Posted | Count of Participants | Participants | 30 months |
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| |||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Time from randomization to death by any cause. | Posted | Median | 95% Confidence Interval | months | With a median follow-up of 12 (0.9-52.2) months |
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| |||||||||||||||||||||||||||
| Secondary | Changes in the Use of Glucocorticoids | Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution | Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution | Posted | Count of Participants | Participants | 30 months |
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Adverse events will be monitored from first dose of study treatment until 30+/-3 days after end of treatment, an average of three years Events will be followed up until resolved or deemed irreversible, which what happens later.
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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 | Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Patients with recurrent anaplastic (Grade III) oligodendrogliomas ith preservation of activity of the RB protein. | 16 | 34 | 7 | 34 | 24 | 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ataxia - G2 | Nervous system disorders | MedDRA 10.0 | Systematic Assessment | No relation; Intensity: Hospitalization; Action: None |
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| Cognitive disturbance - G3 | General disorders | MedDRA 10.0 | Systematic Assessment | No relation; Intensity: Hospitalization; Action: Delay of treatment |
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| Seizure - G2 | General disorders | MedDRA 10.0 | Systematic Assessment | Relation:No; Intensity: Hospitalization; Action: None |
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| Dysphasia - G3 | General disorders | MedDRA 10.0 | Systematic Assessment | Relation: No; Intensity: Hospitalization; Action: None |
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| Surgical and medical procedures - Other, glioma exeresis - G1 | Surgical and medical procedures | MedDRA 10.0 | Systematic Assessment | No Relation; Intensity: Relevant medical; Action:None |
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| Cognitive impairment - G3 | General disorders | MedDRA 10.0 | Systematic Assessment | Relation: No; Intensity: Hospitalization; Action: None |
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| General disorders and administration site conditions - Other, clinical deterioration - G3 | General disorders | MedDRA 10.0 | Systematic Assessment | Relation: No; Intensity: Hospitalization; Action: None |
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| Hyperglycaemia - G4 | Metabolism and nutrition disorders | MedDRA 10.0 | Systematic Assessment | Relation: No; Intensity: Hospitalization; Action:None |
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| Confusion - G3 | General disorders | MedDRA 10.0 | Systematic Assessment | Relation:No; Intensity: Hospitalization; Interruption of treatment |
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| Muscle weakness left-sided - G2 | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment | Relation: No Intensity: Hospitalization. Action: None |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Immune system disorders | MedDRA 10.0 | Systematic Assessment |
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| Fatigue | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Platelet count decreased | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Cognitive disturbance | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Flu like symptoms | General disorders | MedDRA 10.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Cephalea | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Muscle weakness left-sided | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Fever | General disorders | MedDRA 10.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| Confusion | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
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| Cognitive impairment | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
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| White blood cell decreased | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
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| Injury, poisoning and procedural complications - other, Lip wound | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
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| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| A responsibility person designate by sponsor | MFAR | 934344412 | investigacion@mfar.net |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 29, 2022 | Feb 8, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009837 | Oligodendroglioma |
| D001254 | Astrocytoma |
| ID | Term |
|---|---|
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
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| ID | Term |
|---|---|
| C500026 | palbociclib |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| ECOG 2 |
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