Clinical Trials /

Palbociclib + Ganitumab In Ewing Sarcoma

NCT04129151

Description:

This research study is designed to study the combination of two drugs, palbociclib and ganitumab, as a potential treatment for Ewing sarcoma. The names of the study drugs involved in this study are: - Palbociclib - Ganitumab

Related Conditions:
  • Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Palbociclib + Ganitumab In Ewing Sarcoma
  • Official Title: Phase 2 Trial of Palbociclib and Ganitumab in Patients With Relapsed or Refractory Ewing Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 19-373
  • NCT ID: NCT04129151

Conditions

  • Ewing Sarcoma
  • Ewing's Sarcoma Recurrent

Interventions

DrugSynonymsArms
PalbociclibIbrance®PALBOCICLIB and GANITUMAB
GanitumabAMG-479PALBOCICLIB and GANITUMAB

Purpose

This research study is designed to study the combination of two drugs, palbociclib and ganitumab, as a potential treatment for Ewing sarcoma. The names of the study drugs involved in this study are: - Palbociclib - Ganitumab

Detailed Description

      This research study involves participants taking a medicine that inhibits proteins in cancer
      cells called CDK4 and CDK6 (palbociclib) in combination with a medicine that inhibits a
      protein called IGF-1R (ganitumab). This study is designed to see if these drugs are safe when
      given together and whether they are effective in treating Ewing sarcoma.

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug or drug combination to learn whether the drug(s)
      works in treating a specific disease. "Investigational" means that the drug or combination is
      being studied.

      The U.S. Food and Drug Administration (FDA) has not approved ganitumab as a treatment for any
      disease.

      The U.S. Food and Drug Administration (FDA) has not approved palbociclib for this specific
      disease but it has been approved for another cancer.

      This research study is:

        -  Testing whether palbociclib and ganitumab are safe when given together and effective in
           treating Ewing sarcoma.

        -  Testing markers in the blood and in tumor tissue to see if there are certain features of
           the tumor that may indicate this combination of drugs is effective or not effective
    

Trial Arms

NameTypeDescriptionInterventions
PALBOCICLIB and GANITUMABExperimentalThe research study procedures include screening for eligibility and study treatment including evaluations for testing and follow up visits. The study treatment will be 12 months in duration and follow up will be one year from when the participant receives the last dose of study drug. The names of the study drugs involved in this study are: Palbociclib-Oral, per protocol pre determined dosage, once a day for 21 days Ganitumab-Intravenous, per protocol predetermined dosage, twice per cycle Cycle is 28 days
  • Palbociclib
  • Ganitumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 12 years and ≤ 50 years at time of enrollment.

          -  Karnofsky performance status ≥ 50% for patients ≥16 years of age and Lansky ≥ 50% for
             patients <16 years of age (see Appendix A)

          -  Disease Requirement: Participants must have relapsed or refractory Ewing sarcoma with:

               -  RECIST measurable disease at study entry, including at least one RECIST
                  measurable site that has either not been previously radiated or that has had
                  progression after prior radiotherapy;

               -  Histologic diagnosis consistent with Ewing sarcoma or PNET; and

               -  Molecular evidence of translocation involving EWSR1 or FUS (also known as TLS),
                  such as FISH, RT-PCR, or next generation sequencing. If the translocation partner
                  is known it must be of the ETS family (i.e. FLI1 or ERG).

          -  Participants must have disease for which standard curative or palliative measures do
             not exist or are no longer effective.

          -  Patients must have fully recovered (Common Terminology Criteria for Adverse Events
             [CTCAE] version 5 Grade ≤1) from the acute toxic effects of all prior anti-cancer
             therapy except organ function as noted in Section 3.1.6. Patients must meet the
             following minimum washout periods prior to enrollment:

          -  Myelosuppressive chemotherapy: At least 14 days after the last dose of
             myelosuppressive chemotherapy (42 days for nitrosourea or mitomycin C).

          -  Radiotherapy:

               -  At least 14 days after local palliative XRT (small port);

               -  At least 90 days must have elapsed after craniospinal XRT or if >50% radiation of
                  pelvis;

               -  At least 6-months must have elapsed following TBI or thoracic radiation involving
                  the lungs;

               -  At least 42 days must have elapsed if other substantial bone marrow radiation;

          -  Small molecule biologic therapy: At least 7 days following the last dose of a biologic
             agent. For agents with known adverse events occurring beyond 7 days, this duration
             must be extended beyond the time in which adverse events are known to occur. If
             extended duration is required, this should be discussed and approved by the study
             chair.

          -  Monoclonal antibody: At least 21 days must have elapsed after the last dose of
             antibody.

          -  Myeloid growth factors: At least 14 days following the last dose of long-acting growth
             factor (e.g. Neulasta®) or 7 days following short-acting growth factor.

          -  Immunotherapy: At least 4 weeks since the completion of immunotherapy (e.g. tumor
             vaccines) aside from monoclonal antibodies with immune effects covered under Section
             3.1.5.4.

          -  Stem Cell Infusion or Cellular Therapies: The patient must have no evidence of graft
             versus host disease and at least 42 days must have elapsed after transplant, stem cell
             infusion, or cellular therapy.

          -  Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Biopsy and
             central line placement/removal are not considered major surgery.

          -  CDK4/6 and IGF-1R inhibitors: The participant must not have received a prior CDK4/6
             inhibitor. Prior therapy with IGF-1R inhibitor is allowed if the patient did not
             relapse while on IGF-1R therapy. Patients must not have received prior therapy with a
             combination of CDK4/6 inhibitor and IGF-1R inhibitor.

          -  Participants must have normal organ function as defined below.

          -  Hematologic Requirements for Subjects without Known Bone Marrow Involvement by
             Disease:

               -  Absolute neutrophil count ≥ 1000 /uL

               -  Hemoglobin ≥ 8 g/dL (transfusion allowed)

               -  Platelets ≥100,000 /uL and transfusion independent, defined as not receiving a
                  platelet transfusion for at least 7 days prior to CBC documenting eligibility.

          -  Hematologic Requirements for Subjects with Bone Marrow Involvement by Disease as
             Demonstrated on Clinically-Indicated Bone Marrow Biopsy:

               -  Absolute neutrophil count >750 /uL

               -  Hemoglobin ≥ 8 g/dL (transfusion allowed)

               -  Platelets ≥50,000 /uL and transfusion independent, defined as not receiving a
                  platelet transfusion for at least 7 days prior to CBC documenting eligibility.

               -  Not known to be refractory to platelet or red cell transfusions.

          -  Hepatic Function:

               -  Total bilirubin ≤ 1.5 x upper limit of normal for age Patients with Gilbert's
                  syndrome with a total bilirubin < 2 x upper limit of normal for age and a direct
                  bilirubin within normal limits are permitted.

               -  ALT (SGPT) ≤ 135 U/L For the purpose of this study, the ULN for ALT is 45 U/L

               -  AST (SGOT)≤ 90 U/L For the purpose of this study, the ULN for AST is 90 U/L

               -  Serum albumin ≥ 2 g/dL

          -  Renal Function:

             -- A serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL)
             Male Female

               -  12 to < 13 years 1.2 1.2

               -  13 to < 16 years 1.5 1.4

               -  ≥ 16 years 1.7 1.4 Or

          -  Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine levels above
             institutional normal.

          -  Adequate Cardiac Function: QTc ≤ 480 msec on ECG

          -  Adequate GI Function: Diarrhea < grade 2 by CTCAE version 5

          -  Adequate Metabolic Function: Fasting glucose ≤ 160 mg/dL (or < 8.9 mmol/L) without the
             use of antihyperglycemic agents. If random glucose ≤ 160 mg/dL (or ≤ 8.9 mmol/L),
             fasting value does not need to be obtained.

          -  Additional Agent-Specific Requirements

               -  Patients must be able to swallow capsules.

               -  For patients with CNS metastatic disease, any baseline neurologic deficits
                  (including seizure) must be stable for at least one week prior to study
                  enrollment.

          -  Ability to understand and/or the willingness of the patient (or parent or legally
             authorized representative, if minor) to provide informed consent, using an
             institutionally approved informed consent procedure.

        Exclusion Criteria:

          -  Patients must not be receiving any of the following concomitant medications:

             -- Pharmacologic doses of systemic corticosteroids unless for CNS metastatic disease.
             For patients with CNS metastatic disease receiving corticosteroids, they should be on
             a stable or decreasing dose over the 7 days prior to registration Section 3.1.6.7 of
             protocol document. For all patients, receipt of systemic physiologic replacement
             steroids, topical and/or inhaled corticosteroids is acceptable.

          -  Patients receiving medications that are strong inhibitors or inducers of CYP3A4 within
             7 days of enrollment (refer to Appendix B, Table 10 for prohibited medications)

          -  Patients receiving medications that cause significant QTc prolongation as outlined in
             Table 12 of Appendix B.

          -  Patients who have had tumor molecular testing with sequencing of the RB1 gene and were
             found to have RB1 mutation or loss will be excluded.

          -  Patients with a history of pneumonitis will be excluded.

          -  Pregnant participants will not be entered on this study given that the effects of
             palbociclib and ganitumab on the developing human fetus are unknown.

          -  Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with palbociclib and ganitumab, breastfeeding
             mothers are not eligible.

          -  Participants of child-bearing or child-fathering potential must agree to use adequate
             contraception (hormonal birth control; intrauterine device; double barrier method; or
             total abstinence) throughout their participation, including up until 30 days after
             last dose of palbociclib or ganitumab, whichever was administered last.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to palbociclib or ganitumab.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Participants with a personal history of any of the following: syncope due to an
             intrinsic cardiac etiology (note that syncope due to vasovagal episodes or
             dehydration/orthostasis would NOT exclude a participant), pathologic ventricular
             arrhythmias (including, but not limited to, ventricular tachycardia and ventricular
             fibrillation), or sudden cardiac arrest.

          -  Patients with known HIV, hepatitis B, and/or hepatitis C (testing not required as part
             of screening).

          -  Patients with a known history of type 1 or type 2 diabetes mellitus.

          -  Patients with gastrointestinal disease or disorder that could interfere with
             absorption of palbociclib, such as bowel obstruction or inflammatory bowel disease.

          -  Patients < 40 kg will be excluded given use of palbociclib at non-weight / non-BSA
             based flat dosing.
      
Maximum Eligible Age:50 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective overall response rate
Time Frame:12 months
Safety Issue:
Description:Percent of patients with response by RECIST version 1.1

Secondary Outcome Measures

Measure:Progression-free survival rate
Time Frame:2 Years
Safety Issue:
Description:Proportion of patients without progression using Kaplan-Meier methods
Measure:Overall survival rate
Time Frame:2 Years
Safety Issue:
Description:Proportion of patients alive using Kaplan-Meier methods

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Relapsed or refractory Ewing sarcoma
  • Solid Tumor, Childhood
  • Sarcoma
  • Ewing sarcoma

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