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

January 22, 2024 updated by: Grupo Espanol de Investigacion en Sarcomas

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

Non-randomized, open, two-cohort, phase II, multicenter national clinical trial. 20 sites in Spain.

Cohort 1 includes soft-tissue sarcoma and osteosarcoma (21 patients), while Cohort 2 includes chordoma patients only (19 patients).

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Germans Trias i Pujol
        • Contact:
          • Anna Estival
      • Barcelona, Spain
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
          • Antonio Lopez-Pousa, MD
      • Barcelona, Spain
        • Recruiting
        • Institut Català d'Oncologia L'Hospitalet
        • Contact:
          • Xavier García del Muro
      • León, Spain
        • Recruiting
        • Complejo Asistencial Universitario de León
        • Contact:
          • Luís Miguel de Sande
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario 12 de Octubre
        • Contact:
          • Diego Jara, MD
      • Madrid, Spain
        • Recruiting
        • Hospital General Universitario Gregorio Marañon
        • Contact:
          • Rosa Álvarez
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario La Paz
        • Contact:
          • Andres Redondo
      • Madrid, Spain
        • Recruiting
        • Hospital Clinico San Carlos
        • Contact:
          • Antonio Casado
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
        • Contact:
          • Javier Martin Broto
      • Murcia, Spain
        • Recruiting
        • Hospital Clinico Universitario Virgen de la Arrixaca
        • Contact:
          • Jerónimo Martínez
      • Málaga, Spain
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
        • Contact:
          • Isabel Sevilla, MD
      • Oviedo, Spain
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
          • Juan Luís García Llanos, MD
      • Palma De Mallorca, Spain
        • Recruiting
        • Hospital Universitari Son Espases
        • Contact:
          • Pablo Luna
      • Santa Cruz De Tenerife, Spain
        • Recruiting
        • Hospital Universitario de Canarias
        • Contact:
          • Josefina Cruz
      • Santiago de Compostela, Spain
        • Recruiting
        • Complejo Hospitalario Universitario de Santiago
        • Contact:
          • Yolanda Vidal, MD
      • Sevilla, Spain, 41013
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
          • Irene Carrasco García
      • Valencia, Spain
        • Recruiting
        • Hospital Universitari i Politecnic La Fe
        • Contact:
          • Roberto Díaz, MD
      • Valencia, Spain
        • Recruiting
        • Instituto Valenciano de Oncologia
        • Contact:
          • Javier Lavernia
      • Zaragoza, Spain
        • Recruiting
        • Hospital Universitario Miguel Servet
        • Contact:
          • Javier Martínez Trufero, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (Cohort 1: STS and osteosarcoma):

  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 (Cohort 1: STS and osteosarcoma):

  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.

Inclusion Criteria (Cohort 2: Chordomas):

  1. Mutation of CDKN2A gen.
  2. ECOG 0-1 at the time of inclusion.
  3. Centrally confirmed diagnosis of chordoma (metastatic or locally advanced inoperable).
  4. Disease progression according to RECIST 1.1, within the year prior to inclusion, to previous treatment (surgery, radiotherapy or systemic treatment).
  5. Patients are not candidates for salvage surgery or radiotherapy at the time of inclusion.

  6. Patients must have the following lab results:

    • Absolute neutrophil count ≥ 1,500/mm3 (1.5 x 109/L);
    • Platelets ≥ 100,000/mm3 (100 x 109/L);
    • Hemoglobin ≥ 9 g/dL (90 g/L);
    • Blood creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min;
    • Total blood 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 there is liver metastasis);
    • Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if there is bone or liver metastasis);
  7. The patients must have signed the written consent to participate in the clinical study, and to provide the tumor blocks in paraffin for the molecular analysis of the screening phase.
  8. Biopsy at baseline if there are no archive tumor samples obtained in the 3 months prior to starting treatment. If there are tumor samples within this period, there should not be subsequent treatments.
  9. Patients may have received up to 3 previous lines of systemic treatment.
  10. Age between 18 and 80 years (both ages included).
  11. Measurable disease according to RECIST 1.1 criteria.
  12. All patients (male and female) of childbearing potential must use effective contraception throughout treatment with palbociclib and for at least 90 days after the last dose. Pregnancy must be ruled out by urine or blood test (negative pregnancy test) for inclusion in the study. Men should be told to consider sperm preservation before starting treatment due to the risks of infertility.

Exclusion Criteria (Cohort 2: Chordomas):

  1. Prior treatment with any anti-CDK4 or immune checkpoint inhibitors.
  2. Diagnosis other than chordoma according to central review.
  3. Patients irradiated in the only available target lesion.
  4. Patients who have received more than three lines for advanced disease.
  5. History of other neoplastic disease with the exception of adequately treated basal cell carcinoma or cervical cancer in situ. This criterion will be individually assessed with the research team.
  6. Severe cardiovascular disease (NYHA >= 2).
  7. Grade 3 toxicity or higher according to CTCAE 5.0 if, in the investigator's opinion, it can significantly interfere with the toxicity of the drug under study.
  8. Patients who have not recovered from previous toxicity up to CTCAE grade 1 due to previous antineoplastic treatment with chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies).
  9. Patients who have not recovered from minor or major surgery or who have had major surgery within 4 weeks prior to the start of study treatment.
  10. Metastases in the central nervous system.
  11. Patients who are pregnant or lactating, or who expect to conceive children during the treatment period.
  12. Foods or drugs known to be inhibitors/inducers of CYP3A4; CYP3A4 substrates with narrow therapeutic windows, or known to prolong the QTc interval.
  13. Major surgery, chemotherapy, radiation therapy, any investigational agent, or other antineoplastic therapy within 4 weeks prior to enrollment. Patients who have received prior radiation therapy to ≥25% of the bone marrow are not eligible, regardless of when received.
  14. 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).
  15. Any of the following within 6 months prior to study drug administration: Myocardial infarction, severe/unstable angina, current NCI-CTCAE version 5.0 Grade ≥ 2 cardiac dysrhythmias, any grade atrial fibrillation, implant coronary/peripheral artery pacemaker, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, symptomatic pulmonary embolism, or interstitial lung disease (ILD).
  16. Known hypersensitivity to any PD 0332991 or excipients.
  17. Active or recent suicidal intent or behavior.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Palbocilib
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.
Drug: Palbociclib
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision
Other Names:
  • Ibrance

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) rate
Time Frame: At 6 months
Efficacy measured through the progression free survival (PFS) rate at 6 months, evaluated with RECIST 1.1 criteria.
At 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 6 months
Efficacy measured through the overall 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.
6 months
Efficacy measured through response according to Choi criteria measured through response according to Choi criteria:
Time Frame: 6 months
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.
6 months
Efficacy measured through median PFS
Time Frame: 6 months
Efficacy measured through median PFS.
6 months
Efficacy measured through PFS rate at 3 months
Time Frame: 3 months
Efficacy measured through PFS rate at 3 months.
3 months
Overall survival (OS)
Time Frame: 2 years
Overall survival (OS) measured from the date of treatment initiation with palbociclib until date of death, whichever the cause.
2 years
Clinical Benefit Rate (CBR)
Time Frame: 6 months
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.
6 months
Palbociclib safety profile
Time Frame: 1 year
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 (first cohort; STS and osteosarcoma) and 5.0 (second cohort; chordomas).
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Grupo Espanol de Investigacion en Sarcomas

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Javier Martínez Trufero, MD, Hospital Miguel Servet
  • Study Director: Irene Carrasco García, MD, Hospitales Universitarios Virgen del Rocío
  • Study Director: Roberto Díaz, MD, Hospital Universitario la Fe
  • Principal Investigator: Yolanda Vidal, MD, Complejo Hospitalario Universitario de Santiago
  • Principal Investigator: Juan Luís García Llano, MD, Hospital Universitario Central de Asturias
  • Principal Investigator: Antonio López-Pousa, MD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  • Principal Investigator: Diego Jara, MD, Hospital Universitario 12 de Octubre
  • Principal Investigator: Isabel Sevilla, MD, Hospital Universitario Virgen de la Victoria
  • Principal Investigator: Javier Martín Broto, Hospital Universitario Fundacion Jimenez Diaz
  • Principal Investigator: Anna Estival, Germans Trias i Pujol Hospital
  • Principal Investigator: Luís Miguel de Sande, Complejo Asistencial Universitario de León
  • Principal Investigator: Rosa Álvarez, Hospital General Universitario Gregorio Marañon
  • Principal Investigator: Claudia Valverde, Hospital Universitari Vall d'Hebron
  • Principal Investigator: Andrés Redondo, Hospital Universitario La Paz
  • Principal Investigator: Josefina Cruz, Hospital Universitario de Canarias
  • Principal Investigator: Javier Lavernia, Instituto Valenciano de Oncologia
  • Principal Investigator: Pablo Luna, Hospital Son Espases
  • Principal Investigator: Jerónimo Martínez, Hospital Clinico Universitario Virgen de la Arrixaca
  • Principal Investigator: Xavier García del Muro, Institut Català d'Oncologia L'Hospitalet
  • Principal Investigator: Antonio Casado, Hospital San Carlos, Madrid

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 31, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GEIS-51

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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