Clinical Trials /

Pilot Trial of Eltrombopag in Patients Undergoing Chemotherapy for Malignant Solid Tumors

NCT04485416

Description:

Primary Objective: To assess safety of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Secondary Objectives: To assess the efficacy of eltrombopag in increasing platelet count up to 2 weeks after completion of chemotherapy in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Hypothesis: The hypothesis is that eltrombopag an oral thrombopoietin receptor agonist will increase the platelet count safely and efficaciously in children having chemotherapy induced thrombocytopenia while on therapy for solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Trial of Eltrombopag in Patients Undergoing Chemotherapy for Malignant Solid Tumors
  • Official Title: Open Label Single Arm Prospective Pilot Trial of Eltrombopag in Patients 1 Year to 18 Years of Age Undergoing Intensive Chemotherapy for Malignant Solid Tumors (CCPO011)

Clinical Trial IDs

  • ORG STUDY ID: 1602666
  • SECONDARY ID: 150124
  • SECONDARY ID: CCPO011
  • NCT ID: NCT04485416

Conditions

  • Solid Tumor, Childhood
  • Solid Tumor

Interventions

DrugSynonymsArms
EltrombopagPromactaTreatment group

Purpose

Primary Objective: To assess safety of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Secondary Objectives: To assess the efficacy of eltrombopag in increasing platelet count up to 2 weeks after completion of chemotherapy in pediatric patients undergoing intensive chemotherapy for malignant solid tumors. Hypothesis: The hypothesis is that eltrombopag an oral thrombopoietin receptor agonist will increase the platelet count safely and efficaciously in children having chemotherapy induced thrombocytopenia while on therapy for solid tumors.

Detailed Description

      Eltrombopag is an orally administered, small molecule thrombopoietin receptor (TPO-R) agonist
      that stimulates platelet production by a mechanism similar, but not identical to endogenous
      TPO. Eltrombopag interacts with the transmembrane domain of the TPO-R (also known as C-MPL)
      leading to increased platelet production (Erickson-Miller, 2010; Sun et al, 2012).

      Eltrombopag is indicated for the treatment of thrombocytopenia in adult and pediatric
      patients one year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have
      had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

      Eltrombopag has also been approved for the treatment of thrombocytopenia in adult patients
      with chronic hepatitis C to allow for the initiation and maintenance of interferon-based
      therapy and for the treatment of cytopenias in adult patients with severe aplastic anemia
      (SAA) who have had insufficient responses to immunosuppressive therapy.

      This is an open label, single center pilot trial of eltrombopag in pediatric patients
      receiving cancer directed therapy for solid tumors. The purpose of this study is to explore
      the platelet supportive care effects and safety of eltrombopag in pediatric patients (ages
      one to 18 years of age) undergoing intensive chemotherapy for malignant solid tumors. The
      primary endpoint will be to determine the safety of eltrombopag in pediatric patients
      undergoing intensive chemotherapy for malignant solid tumors using CTCAE v5.0 criteria. The
      secondary endpoint will be to determine the efficacy of eltrombopag in pediatric patients
      undergoing intensive chemotherapy for malignant solid tumors. These objectives will be
      assessed by evaluating drug-related toxicities, the platelet response in patients and the
      proportion of subjects receiving eltrombopag who are platelet transfusion-free during the
      time period of chemotherapy.

      The study will enroll 10 subjects with histologically confirmed solid tumors, including but
      not limited to rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, non-rhabdomyosarcoma soft
      tissue sarcoma, peripheral nerve sheath tumor, desmoplastic small round cell tumor,
      hepatoblastoma, hepatocellular carcinoma, renal cell carcinoma, higher grade neuroblastoma,
      medulloblastoma, or other rare malignant solid tumors.

      The cancer directed therapy will be part of standard treatment for each patient and will
      consist of two to four cycles of chemotherapy (or as many as clinically indicated per
      physician discretion) to reduce tumor burden, followed by surgery in the majority of cases,
      and/or radiation in a minority of cases, or both in rare cases at various times in the course
      of treatment. After recovery from the surgery and/or radiation, chemotherapy and eltrombopag
      will be resumed until completion. Each cycle of chemotherapy will be approximately two to
      four weeks (14 to 28 days) in length with chemotherapy administered for one to five days per
      cycle. The duration of chemotherapy varies by regimen and underlying malignancy.

      Patients will initiate eltrombopag on the first day following the completion of chemotherapy
      for each cycle (e.g., chemo is administered on Days 1-5, eltrombopag to start on Day 6).
      Eltrombopag will be administered daily and the dose will be age dependent (see Table 5).
      Children less than 6 years of age will receive a starting dose of 25 mg by mouth once daily,
      taken on empty stomach one hour before or two hours after a meal. For children greater than
      or equal to 6 years of age, the starting dose will be 75 mg by mouth once daily. Doses shall
      be reduced in patients of Asian ancestry (e.g., Japanese, Chinese, Taiwanese, or Korean): for
      those patients greater than or equal to 6 years of age, the starting dose will be 50 mg by
      mouth once daily and for those patients less than 6 years old, the starting dose will be 12.5
      mg by mouth once daily. Eltrombopag will be continued until the platelets are at least
      100,000/µL after the nadir.

      Subjects will be recruited from the UC Davis Comprehensive Cancer Center or when they are
      admitted to UC Davis Children's Hospital.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment groupExperimentalSubjects will receive eltrombopag
  • Eltrombopag

Eligibility Criteria

        Inclusion Criteria:

        Patients must meet all of the following criteria to be eligible for study entry.

          1. Persons aged ≥ 1 to ≤18 years of age.

          2. Histologically confirmed solid tumors (including rhabdomyosarcoma, Ewings sarcoma,
             osteosarcoma, non- rhabdomyosarcoma soft tissue sarcoma, peripheral nerve sheath
             tumor, desmoplastic small round cell tumor, hepatoblastoma, hepatocellular carcinoma,
             renal cell carcinoma, higher grade neuroblastoma, brain tumors (e.g. medulloblastoma),
             and other rare solid tumors.

          3. Currently receiving cancer directed therapy for solid tumor or scheduled to start
             receiving cancer directed therapy for solid tumor within 60 days.

          4. Karnofsky Performance Status (KPS) performance status of 80% or greater.

          5. Life expectancy ≥ 6 months.

          6. Ability to swallow liquid solution/suspensions or tablets/capsules

          7. Platelet count < 150,000µL

          8. Blood chemistry levels defined by:

               -  Serum creatinine less than or equal to 2.5 × the upper limit of normal (ULN)
                  range

               -  Total bilirubin level less than or equal to 1.5 × the upper limit of normal (ULN)
                  range

               -  AST and ALT < 3 x upper limit of normal (ULN)

          9. INR and aPTT less than or equal to 1.5 × ULN (for patients on anticoagulation they
             must be receiving a stable dose for at least 1 week prior to first treatment)

         10. Ability to understand and willingness to sign an informed consent form; or
             Parent/Guardian with ability to understand and willingness to sign an informed consent
             form.

         11. Ability to adhere to the study visit schedule and other protocol requirements.

        Exclusion Criteria:

        Patients who meet any of the following criteria will be excluded from study entry.

          1. Patients with known with hematologic malignancy diagnosis.

          2. Contraindications to receiving chemotherapy.

          3. Patients with history of thromboembolic disease or history of thrombophilic risk
             factors.

          4. History or current diagnosis of cardiac disease indicating significant risk of safety
             for patients participating in the study such as uncontrolled or significant cardiac
             disease, including any of the following:

               -  Recent myocardial infarction (within last 6 months),

               -  Uncontrolled congestive heart failure,

               -  Unstable angina (within last 6 months),

               -  Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained
                  ventricular tachycardia, and clinically significant second or third degree AV
                  block without a pacemaker.)

               -  Long QT syndrome, family history of idiopathic sudden death, congenital long QT
                  syndrome or additional risk factors for cardiac repolarization abnormality, as
                  determined by the investigator.

          5. Impaired cardiac function, defined as:

               -  Corrected QTc >450 msec using Fridericia correction (QTcF) on the screening ECG
                  (using triplicate ECGs),

               -  Other clinically significant cardio-vascular disease (e.g., uncontrolled
                  hypertension, history of labile hypertension),

               -  History of known structural abnormalities (e.g. cardiomyopathy).

          6. Pregnant or lactating women.

          7. Subjects with liver enzymes 5x upper limit of normal or liver cirrhosis (as determined
             by the investigator).

          8. Patients with known history of HIV positivity.

          9. Patient with known active or uncontrolled infections not responding to appropriate
             therapy.

         10. History of alcohol/drug abuse.

         11. Concurrent participation in an investigational study within 30 days prior to
             enrollment or within 8 days (> than 5-half-lives)of the investigational product,
             whichever is longer. Note: parallel enrollment in a disease registry is permitted.

         12. Known thrombophilic risk factors or history of thromboembolic disease. Exception:
             Subjects for whom the potential benefits of participating in the study outweigh the
             potential risks of thromboembolic events, as determined by the investigator.

         13. Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient.

         14. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using basic methods of contraception during dosing
             of study treatment. Basic contraception methods include:

               -  Total abstinence (when this is in line with the preferred and usual lifestyle of
                  the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
                  taking study treatment. In case of oophorectomy alone, only when the reproductive
                  status of the woman has been confirmed by follow up hormone level assessment

               -  Male sterilization (at least 6 months prior to screening). The vasectomized male
                  partner should be the sole partner for that subject.

               -  Barrier methods of contraception: Condom or Occlusive cap.

               -  Use of oral, injected or implanted hormonal methods of contraception or placement
                  of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
                  hormonal contraception that have comparable efficacy (failure rate <1%), for
                  example hormone vaginal ring or transdermal hormone contraception. In case of use
                  of oral contraception women should have been stable on the same pill for a
                  minimum of 3 months before taking study treatment.

         15. Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic
             gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1.

         16. Sexually active males unless they use a condom during intercourse while taking the
             drug during treatment, and for 8 days (> 5 half-lives ) after stopping eltrombopag and
             for 5 half-lives after the last dose of chemotherapy treatment and should not father a
             child in this period. A condom is required to be used also by vasectomized men as well
             as during intercourse with a male partner in order to prevent delivery of the drug via
             semen.

         17. Any condition that would prohibit the understanding or rendering of informed consent.

         18. Any condition that in the opinion of the investigator would interfere with the
             patient's safety or compliance on trial.

         19. Severe infection within 4 weeks prior to enrollment that in the opinion of the
             investigator would interfere with patient safety or compliance on trial.
      
Maximum Eligible Age:18 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety objectives
Time Frame:Through follow up after end of treatment
Safety Issue:
Description:For safety our end point is liver enzymes ALT, AST up to 5 x upper limit of normal (ULN) in <80% of patients.

Secondary Outcome Measures

Measure:Efficacy objectives
Time Frame:2 weeks after completion of chemotherapy
Safety Issue:
Description:For efficacy the end point is 6 of 10 patients respond to the study treatment by an increase in platelet counts by 20,000/μL and are able to proceed with their next cycle of chemotherapy.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Anjali Pawar

Trial Keywords

  • chemotherapy
  • pediatric

Last Updated

July 23, 2021