Clinical Trials /

Trial of Palbociclib in Second Line of Advanced Sarcomas With CDK4 Overexpression.

NCT03242382

Description:

Non-randomized, open, single cohort, phase II, multicenter national clinical trial. 19 sites in Spain. Palbociclib will be administered orally at a dose of 125 mg once a day for 21 consecutive days followed by 7 rest days to comprise a complete cycle of 28 days. Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision The main goal is to determine progression-free survival rate (PFSR) according to RECIST 1.1 at 6 months

Related Conditions:
  • Osteosarcoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Palbociclib in Second Line of Advanced Sarcomas With CDK4 Overexpression.
  • Official Title: Phase II Multicenter Trial of Palbociclib in Second Line of Advanced Sarcomas With CDK4 Overexpression.

Clinical Trial IDs

  • ORG STUDY ID: GEIS-51
  • NCT ID: NCT03242382

Conditions

  • Sarcoma
  • Advanced Cancer

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbocilib

Purpose

Non-randomized, open, single cohort, phase II, multicenter national clinical trial. 19 sites in Spain. Palbociclib will be administered orally at a dose of 125 mg once a day for 21 consecutive days followed by 7 rest days to comprise a complete cycle of 28 days. Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision The main goal is to determine progression-free survival rate (PFSR) according to RECIST 1.1 at 6 months

Trial Arms

NameTypeDescriptionInterventions
PalbocilibExperimentalPalbociclib will be administered orally at a dose of 125 mg once a day for 21 consecutive days followed by 7 rest days to comprise a complete cycle of 28 days.
  • Palbociclib

Eligibility 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, two or three 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.

        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 three 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.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS) rate
Time Frame:At 6 months
Safety Issue:
Description:Efficacy measured through the progression free survival (PFS) rate at 6 months, evaluated with RECIST 1.1 criteria.

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:6 months
Safety Issue:
Description: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.
Measure:Efficacy measures through response according to Choi criteria measured through response according to Choi criteria:
Time Frame:6 months
Safety Issue:
Description:Efficacy measures 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.
Measure:Efficacy measured through median PFS.
Time Frame:6 months
Safety Issue:
Description:Efficacy measured through median PFS. measured through median PFS:
Measure:Efficacy measured through PFS rate at 3 months.
Time Frame:3 months
Safety Issue:
Description:Efficacy measured through PFS rate at 3 months.
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:Overall survival (OS) measured from the date of treatment initiation with palbociclib until date of death, whichever the cause.
Measure:Clinical Benefit Rate (CBR)
Time Frame:6 months
Safety Issue:
Description: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.
Measure:Palbociclib safety profile
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Grupo Espanol de Investigacion en Sarcomas

Trial Keywords

  • advanced
  • sarcoma
  • cdk4

Last Updated

April 30, 2020