Trial Title:
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
NCT ID:
NCT05734066
Condition:
Refractory Ewing Sarcoma
Relapsed Ewing Sarcoma
Ewing Sarcoma
Conditions: Official terms:
Sarcoma
Sarcoma, Ewing
Conditions: Keywords:
Solid Tumors
lurbinectedin
ewing's sarcoma
soft tissue sarcoma
sarcomas
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Lurbinectedin
Description:
Administered as intravenous (IV) infusion once every 3 weeks (Q3W)
Arm group label:
Phase 1 Part 1: Dose Selection
Arm group label:
Phase 1 Part 2: RP2D
Arm group label:
Phase 2
Other name:
JZP712
Summary:
This study is conducted in two phases. The phase 1 portion of the study evaluates the
safety, tolerability, pharmacokinetics (PK), recommended phase 2 dose (RP2D), and
effectiveness of lurbinectedin monotherapy in pediatric participants with previously
treated solid tumors. This is followed by the phase 2 portion, to further assess the
effectiveness and safety in pediatric and young adult participants with
recurrent/refractory Ewing sarcoma.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
Age
- Participant must meet the following age requirements at the time the informed
consent form (ICF) (and assent form, if applicable) is signed:
- Phase 1 Part 1: participants must be ≥ 2 to < 18 years of age.
- Phase 1 Part 2: participants must be ≥ 2 to ≤ 30 years of age.
- Phase 2: participants must be ≥ 2 to ≤ 30 years of age.
Type of Participant and Disease Characteristics
- Participant has a confirmed solid tumor
- The participant has a Lansky/Karnofsky performance status score of ≥ 50%.
- The participant has adequate liver function, evidenced by the following laboratory
values:
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × upper
limit of normal (ULN).
- Total bilirubin ≤ 1.5 × institutional ULN (with the exception of participants
with Gilbert's syndrome who must have bilirubin < 3 × institutional ULN).
- The participant has adequate bone marrow function, evidenced by the following:
- Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (independent of growth factor
support within 1 week of screening laboratories).
- Platelets ≥ 100 × 109/L (without platelet transfusion within previous 7 days of
screening laboratories).
- Hemoglobin ≥ 8 g/dL (note: may have been transfused).
- The participant has an adequate renal function:
- Calculated creatinine clearance (use Cockcroft-Gault formula for participants ≥
18 years; Schwartz equation for participants < 18 years) ≥ 60 mL/min.
- The participant has an adequate cardiac function:
- Left ventricular ejection fraction or shortening fraction per institutional
norm ≥ institutional lower level of normal.
- The participant has creatine phosphokinase ≤ 2.5 × institutional ULN.
Weight
- The participant has body weight ≥ 15 kg.
Sex and Contraceptive/Barrier Requirements
Male participants:
Male participants are eligible to participate if they agree to the following during the
study intervention period and for at least 4 months after the last dose of study
intervention:
- Refrain from donating sperm.
PLUS, either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
(abstinent on a long-term and persistent basis) and agree to remain abstinent.
OR
- Must agree to use contraception/barrier as detailed below:
- Agree to use a male condom with female partner and use of an additional highly
effective contraceptive method with a failure rate of < 1% per year when having
sexual intercourse with a Woman of childbearing potential (WOCBP) who is not
currently pregnant.
- Note: male participants who are azoospermic (vasectomized or due to a medical
cause) are still required to follow the protocol-specified
contraception/barrier criteria.
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding,
and one of the following conditions applies:
- Is a Woman of nonchildbearing potential (WONCBP). OR
- Is a WOCBP and using an acceptable contraceptive method during the study
intervention period (at least 7 months after the last dose of study intervention).
The investigator should evaluate the potential for contraceptive method failure (eg,
noncompliance, recently initiated) in relationship to the first dose of study
intervention.
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 7 days before the first dose of study
intervention.
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be
excluded from participation if the serum pregnancy result is positive.
- Additional requirements for pregnancy testing during and after study intervention.
- The investigator is responsible for review of medical history, menstrual history,
and recent sexual activity to decrease the risk for inclusion of a woman with an
early undetected pregnancy.
Informed Consent
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
Key Exclusion Criteria:
Medical Conditions
- corrected QT interval (QTc) prolongation defined as a QTc ≥ 470 ms using the Bazett
formula.
- Known symptomatic Central nervous system (CNS) metastases requiring steroids.
Participants with previously diagnosed CNS metastases are eligible if they have
completed their treatment and have recovered from the acute effects of radiation
therapy or surgery prior to enrollment, have discontinued high dose steroid
treatment for these metastases for at least 2 weeks, and are neurologically stable
(physiologic doses of steroids and short courses of steroids for other indications
are acceptable).
- Persisting toxicity related to prior therapy; however, alopecia, sensory neuropathy,
hypothyroidism, and rash Grade ≤ 2 are acceptable, and other Grade ≤ 2 adverse
events (AEs) not constituting a safety risk based on the investigator's judgement
are acceptable.
- An uncontrolled intercurrent illness including but not limited to ongoing or active
infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart
failure, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.
- Any other major illness that, in the investigator's judgment, could substantially
increase the risk associated with participation in this study.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the participant at high-risk for treatment
complications.
Prior/Concomitant Therapy
- Received prior treatment with lurbinectedin or trabectedin.
- Received prior treatment with any investigational product within 4 weeks of first
infusion of study intervention. Observational studies are permitted.
- Received live or live attenuated vaccines within 4 weeks of the first dose of study
treatment or plans to receive live vaccines during study participation.
Administration of inactive vaccines or messenger ribonucleic acid (mRNA) vaccines
(for example, inactivated influenza vaccines or COVID-19 vaccines) are allowed.
- Had major surgery ≤ 4 weeks or radiation therapy ≤ 2 weeks prior to enrollment
unless fully recovered. Prior palliative radiotherapy is permitted, provided it was
completed at least 2 weeks prior to participant enrollment.
- Received prior allogeneic bone marrow transplantation or solid organ transplant.
- Received chemotherapy ≤ 3 weeks prior to start of study intervention.
Diagnostic Assessments
- Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection at screening (positive
HBV surface antigen or Polymerase chain reaction (PCR) test for HCV RNA if HCV
antibody test is positive).
- Human immunodeficiency infection at screening (positive anti-HIV antibody).
Other Exclusions
- Has a known or suspected hypersensitivity to any of the components of the study
intervention.
- The participant or parent(s)/guardian(s) is/are unable to comply with the study
visit schedule and other protocol requirements, in the opinion of the investigator
Gender:
All
Minimum age:
2 Years
Maximum age:
30 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Children's Hospital Los Angeles
Address:
City:
Los Angeles
Zip:
90027
Country:
United States
Status:
Recruiting
Facility:
Name:
Stanford Children's Health
Address:
City:
Palo Alto
Zip:
94304
Country:
United States
Status:
Recruiting
Facility:
Name:
Childrens National Hospital Michigan
Address:
City:
Washington
Zip:
20010
Country:
United States
Status:
Recruiting
Facility:
Name:
Johns Hopkins All Children's Hospital
Address:
City:
Saint Petersburg
Zip:
33701
Country:
United States
Status:
Recruiting
Facility:
Name:
Corewell Health
Address:
City:
Grand Rapids
Zip:
49503
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Facility:
Name:
Cincinnati Children's Hospital Medical Center
Address:
City:
Cincinnati
Zip:
45229
Country:
United States
Status:
Recruiting
Facility:
Name:
Nationwide Childrens
Address:
City:
Columbus
Zip:
43205
Country:
United States
Status:
Recruiting
Facility:
Name:
Children's Hospital of Philadelphia
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Facility:
Name:
St. Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Status:
Recruiting
Facility:
Name:
UT Southwestern in Texas
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
The Hospital for Sick Children
Address:
City:
Toronto
Zip:
M5G 1X8
Country:
Canada
Status:
Recruiting
Start date:
May 23, 2023
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Jazz Pharmaceuticals
Agency class:
Industry
Source:
Jazz Pharmaceuticals
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05734066
