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.
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
Drug | Synonyms | Arms |
---|
Eltrombopag | Promacta | Treatment 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
Name | Type | Description | Interventions |
---|
Treatment group | Experimental | Subjects will receive 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
Last Updated
July 23, 2021