Patients with advanced soft tissue sarcomas and osteosarcomas
Conditions
Interventions
Trade Name: Ibrance
Product Name: Ibrance
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PALBOCICLIB
CAS Number: 571190-30-2
Current Sponsor code: PD-0332991
Concentration unit: mg milligram(
Sponsors
Grupo Español de Investigación en Sarcomas (GEIS)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Over-expression of CDK4 (mRNA expression) and a low-to-normal p16 expression (mRNA expression) measured in paraffin embedded tumor samples at study entry. 2) ECOG 0-1 at enrollment. 3) Diagnosis of soft tissue sarcoma or osteosarcoma (in both cases with metastasis or locally advanced, unresectable). 4) Disease progression documented within 6 months prior to study entry. 5) Patients must have the following laboratory results: • ANC = 1,500/mm3 (1.5 x 109/L); • Platelets = 100,000/mm3 (100 x 109/L); • Hemoglobin = 9 g/dL (90 g/L); • Serum creatinine = 1.5 x ULN or estimated creatinine clearance = 60 mL/min; • Total serum bilirubin = 1.5 x ULN (= 3.0 x ULN if Gilbert’s disease); • AST and/or ALT = 3 x ULN (= 5.0 x ULN if liver metastases present); • Alkaline phosphatase = 2.5 x ULN (= 5.0 x ULN if bone or hepatic metastasis present); 6) Patients must have signed written informed consent to participate in the clinical study, and to provide at least two paraffin embedded tumor blocks for the molecular analyses at screening stage. 7) Biopsy at baseline if there are no archived tumor samples obtained within 3 months prior to treatment initiation. 8) Patients must have received standard treatments for at least one or two lines for advanced disease. 9) Age between 18 and 80 years (both ages included). 10) Measurable disease according to RECIST 1.1 criteria. 11) All patients (men and women) in fertile age must use an effective contraception method during the entire treatment with palbociclib and for at least 90 days after the last dose. Pregnancy must be ruled out through urine or blood test (negative pregnancy test) for the inclusion in the study. Men must be informed to consider spermatic preservation before treatment initiation due to infertility risks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 23 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1) Previous treatment with any anti CDK4 or immune checkpoint inhibitor. 2) Diagnosis of Ewing sarcoma or rhabdomyosarcoma. 3) Diagnosis of well differentiated/dedifferentiated liposarcoma. 4) Patients irradiated on the only target lesion available. 5) Patients having received more than two lines for advanced disease. 6) History of other neoplastic disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated. 7) Serious cardiovascular disease (NYHA >= 2) 8) Grade 3 or superior toxicity according to CTCAE 4.0 if the investigator considers this can significantly interfere in the toxicity of the drug under study. 9) Patients not recovered from a previous toxicity to at least CTCAE Grade 1 due to prior chemotherapy, radioactive, or biological cancer therapy (including monoclonal antibodies). 10) Patients not recovered from minor or major surgery or having undergone a major surgery within the last 4 weeks prior to initiation of study treatment. 11) Central nervous system metastasis. 12) Pregnant or breastfeeding patients, or those expecting to conceive or father children within the projected duration of treatment. 13) Foods or drugs known as CYP3A4 inhibitors/inducers; CYP3A4 substrates with narrow therapeutic windows, or known to prolong QTc interval. 14) Major surgery, chemotherapy, radiotherapy, any agent under investigation, or other antineoplastic therapy within 4 weeks prior to inclusion. Patients having received a previous radiotherapy =25% of bone marrow are not eligible, regardless of when it was received. 15) QTc > 480 ms; personal or family history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsades de Pointes (TdP). 16) Any of the following situations within 6 months prior to study drug administration: myocardial infarction, serious/unstable angina, current cardiac dysrhythmias Grade = 2 NCI-CTCAE version 4.0, atrial fibrillation of any grade, bypass graft in coronary/peripheral artery, symptomatic congestive cardiac failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. 17) Known hypersensitivity to any PD 0332991 or excipients. 18) Active or recent suicide attempt or behavior.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: At 6 months;Main Objective: To determine the progression free survival (PFS) rate according to RECIST 1.1 criteria at 6 months;Secondary Objective: • To evaluate objective response rate (ORR) according to RECIST 1.1 • To evaluate response according to Choi criteria • To evaluate median PFS • To evaluate PFS rate at 3 months • To evaluate overall survival (OS) • To evaluate clinical benefit rate (CBR) • To evaluate safety profile according to CTCAE 4.0;Primary end point(s): Efficacy measured through the progression free survival (PFS) rate at 6 months, evaluated with RECIST 1.1 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy measured through the objective response rate (ORR) (complete response [CR] and partial response [PR]), evaluated with RECIST 1.1 criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression. • Efficacy measured through response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression. • Efficacy measured through median PFS. • Efficacy measured through PFS rate at 3 months. • Overall survival (OS) measured from the date of treatment initiation with palbociclib until date of death, whichever the cause. • Clinical Benefit Rate (CBR). Patients having shown complete response, partial response, or disease stabilization during 6 months or more, showing clinical improvement symptoms, will be considered as having experienced clinical benefit. • Palbociclib safety profile, through the evaluation of adverse events (type, incidence, severity, timing of appearance, related causes) observed in physical explorations and laboratory tests. Toxicity will be assessed and tabulated using NCI-CTCAE 4.0;Timepoint(s) of evaluation of this end point: • Efficacy measured through the objective response rate (ORR): 6 months • Efficacy measured through response according to Choi criteria: 6 months • Efficacy measured through median PFS: 6 months • Efficacy measured through PFS rate at 3 months. • Overall survival (OS): 2 years • Clinical Benefit Rate (CBR): 6 months • Palbociclib safety profile, through the evaluation of adverse events: 1 year | — |
Countries
Spain
Contacts
Public ContactClinical Trials
Sofpromed Investigación Clínica, SLU
Outcome results
None listed