Oligoastrocytoma, Oligodendroglioma
Conditions
Keywords
Palbociclib, oligodendroglioma, oligoastrocytoma anaplastic
Brief summary
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.
Interventions
DRUGPalbociclib
Palbociclib will be administered orally at a dose of 125 mg/day, until disease progression, unacceptable adverse side effects or study end.
Sponsors
Pfizer
Grupo Español de Investigación en Neurooncología
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand and sign the informed consent approved by the Ethic Committee. 2. Men or women aged greater than or equal to 18. 3. 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. 4. 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. 5. All patients have to present positivity in immunohistochemical study for the RB protein in the tumor samples sent to the central lab. 6. The cases must have 10 slides or a tumor block available from a biopsy or surgery. 7. All patients have to show disease progression in a cerebral nuclear magnetic resonance. 8. Interval of at least one week between the previous intracranial biopsy and the inclusion. 9. 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. 10. 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. 11. ECOG≤2 12. Stable or decreasing dose of corticoids during the five days prior to the inclusion 13. patients who have been suffered from a tumor resection in the last recurrence are eligible if: * A good surgery recover * there is a measurable or evaluable disease after surgery 14. Good bone marrow function: * Neutrophils ≥ 1500/mm3 (1.5x10e9/L) * Platelet ≥ 100.000/mm3 (100 x 10e9) * Hemoglobin ≥ 9 g/dL * Seric creatinine ≤ 1.5 x LSN of the site or estimated clearance ≥ 60 ml/min calculated. * Bilirubin ≤ 1.5 x LSN (if Gilbert's syndrome ≤ 3 xLSN) AST (SGOT) and/or ALT ≤ 3 x LSN; alkaline phosphatase ≤ 2.5 x LSN. 15. 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
1. Presence of meningeal carcinomatosis disseminated. 2. Concomitant treatment with other investigational products 3. Previous treatment wih an investigational product that could be active for CDK4/6 4. Any kind of surgery in the previous 2 weeks 5. 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. 6. 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. 7. 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 8. QTc interval \>480 msec, familiar history or personal of QT large Syndrome, QT short Syndrome, Brugada syndrome, QTc extension or Torsade de Pointes history 9. Electrolyte disorder that may affect the QTc interval 10. Significant or uncontrolled cardiovascular disease, including: * Myocardial infarction within the previous 12 months * Uncontrolled angina within the previous 6 months * Congestive heart failure in the previous 6 months * History of clinically significant ventricular arrhythmias of any type (as ventricular tachycardia, ventricular fibrillation or torsades de pointes) * History of second or third grade heart block (these patients may be eligible if you currently have a pacemaker) * Ictus * Pulmonary embolism 11. History of any cancer, except for the following circumstances: * Patients with a history of other malignancies are eligible if they have been free of disease for at least the last 3 years, and at the discretion of the investigator, there is low risk of disease recurrence. * Patients with the following cancers are eligible even if they are diagnosed and treated in the last 3 years: carcinoma in situ of the cervix and basal cell or basal cell skin carcinoma. Patients are ineligible if there is evidence of any neoplastic disease that required therapy other than surgery in the past 3 years. 12. Patients positive for HIV 13. Inflammatory bowel disease, chronic diarrhea, short gut syndrome or any upper gastrointestinal surgery including gastric resection. 14. History of allergic reactions to Palbociclib 15. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) at Six Months (PFS6m) | 6 months | Percentage of patients who have progressed / no progress after 6 months of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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.) | Three years | 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. |
| Anti-tumor Response According to RANO Criteria | 30 months | According to RANO criteria, assessed by the PI of each center. There will be a central review. |
| Overall Survival (OS) | With a median follow-up of 12 (0.9-52.2) months | Time from randomization to death by any cause. |
| Changes in the Use of Glucocorticoids | 30 months | Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution |
Countries
Spain
Participant flow
Recruitment details
A total of 79 patients were screened and eventually 34 patients fulfilled all the inclusion and exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. |
|---|---|
| Age, Continuous | 50.7 years |
| ECOG, Categorical ECOG 0 | 10 Participants |
| ECOG, Categorical ECOG 1 | 19 Participants |
| ECOG, Categorical ECOG 2 | 5 Participants |
| Prior treatment Temozolomide Nitrosoureas | 23 Participants |
| Prior treatment Temozolomide Radiotherapy | 34 Participants |
| Prior treatment Temozolomide Temozolamide | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 34 |
| other Total, other adverse events | 24 / 34 |
| serious Total, serious adverse events | 7 / 34 |
Outcome results
Primary
Progression-free Survival (PFS) at Six Months (PFS6m)
Percentage of patients who have progressed / no progress after 6 months of treatment
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Progression-free Survival (PFS) at Six Months (PFS6m) | 21 Percentage of participants |
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.
Time frame: 30 months
Population: Patients with recurrent anaplastic (Grade III) oligodendrogliomas
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Anti-tumor Response According to RANO Criteria | No evaluated | 1 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Anti-tumor Response According to RANO Criteria | Stable disease (SD) | 13 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Anti-tumor Response According to RANO Criteria | Progression disease (PD) | 20 Participants |
Secondary
Changes in the Use of Glucocorticoids
Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution
Time frame: 30 months
Population: Percentage of patients decreasing doses of corticosteroids during treatment. Corticoids evolution
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Changes in the Use of Glucocorticoids | NA or not reported | 7 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Changes in the Use of Glucocorticoids | Decrease | 1 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Changes in the Use of Glucocorticoids | Increase | 3 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Changes in the Use of Glucocorticoids | No corticoids | 21 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Changes in the Use of Glucocorticoids | Stable | 2 Participants |
Secondary
Overall Survival (OS)
Time from randomization to death by any cause.
Time frame: With a median follow-up of 12 (0.9-52.2) months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | Overall Survival (OS) | 32 months |
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.
Time frame: Three years
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | SAE (any) | 7 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | Toxicity grade≥3 | 22 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | Adverse envents (any) | 33 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | Adverse events (≥ Grade 3) | 25 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | TRAEs (any) | 29 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | TRAEs (≥ Grade 3) | 22 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | SAE no related | 7 Participants |
| Patients With Recurrent Anaplastic (Grade III) Oligodendrogliomas. | 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.) | Toxicity (any) | 29 Participants |