A Randomized, Open-Label Phase 1/2 Study Evaluating Ramucirumab in Pediatric Patients and Young Adults With Relapsed, Recurrent, or Refractory Synovial Sarcoma
Overview
- Phase
- Phase 1
- Intervention
- Ramucirumab
- Conditions
- Synovial Sarcoma
- Sponsor
- Eli Lilly and Company
- Enrollment
- 23
- Locations
- 56
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is being conducted to test the safety and efficacy of ramucirumab in combination with other chemotherapy in the treatment of relapsed, recurrent, or refractory synovial sarcoma (SS) in children and young adults. This trial is part of the CAMPFIRE master protocol (NCT05999994) which is a platform to accelerate the development of new treatments for pediatric and young adult participants with cancer. Your participation in this trial could last 12 months or longer, depending on how you and your tumor respond.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must have discontinued all previous treatments for cancer or investigational agents ≥7 days after the last dose or per the type of previous treatment as stated in the protocol and must have recovered from the acute effects to ≤Grade 2 for alopecia and decreased tendon reflex and to ≤Grade 1 for all other effects at the time of enrollment, unless otherwise noted. Consult with the Lilly clinical research physician or scientist for the appropriate length of time prior to the first dose of study treatment.
- •Participants with relapsed, recurrent, or refractory SS.
- •Participants must:
- •Have measurable disease by Response Evaluation Criteria in Solid Tumors, Version (RECIST) 1.
- •have received at least one prior line of systemic treatment (including neoadjuvant and adjuvant chemotherapy) that contains ifosfamide and/or doxorubicin, or any approved therapies for which they are eligible, unless the patient is not a suitable candidate for the approved therapy.
- •not be eligible for surgical resection at time of enrollment.
- •Adequate cardiac function, defined as: Shortening fraction of ≥27% by echocardiogram, or ejection fraction of ≥50% by gated radionuclide study.
- •Adequate blood pressure (BP) control, defined as:
- •Participants ≥18 years: Controlled hypertension defined as systolic BP ≤150 millimeters of mercury (mmHg) or diastolic BP ≤90 mmHg where standard medical management is permitted. Please note that ≥2 serial BP readings should be obtained and averaged to determine baseline BP.
- •Participants \<18 years: A BP ≤95th percentile for age, height, and gender measured as described in National High Blood Pressure Education Program Working Group (NHBPEPWG) on High Blood Pressure in Children and Adolescents (2004), where standard medical management is permitted. Please note that ≥2 serial BP readings should be obtained and averaged to determine baseline BP.
Exclusion Criteria
- •Participants with severe and/or uncontrolled concurrent medical disease or psychiatric illness/social situation that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
- •Participants who have active infections requiring therapy.
- •Participants with an active fungal, bacterial, and/or known severe viral infection including, but not limited to, human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
- •Participants who have had allogeneic bone marrow or solid organ transplant are excluded.
- •Surgery: Participants who have had, or are planning to have, the following invasive procedures are not eligible:
- •Major surgical procedure, laparoscopic procedure, or significant traumatic injury within 28 days prior to enrollment.
- •Central line placement or subcutaneous port placement is not considered major surgery.
- •Core biopsy, fine needle aspirate, and bone marrow biopsy/aspirate are not considered major surgeries.
- •Surgical or other wounds must be adequately healed prior to enrollment.
- •Bleeding and thrombosis:
Arms & Interventions
Ramucirumab + Gemcitabine + Docetaxel
Participants received intravenous (IV) infusions of ramucirumab 9 milligrams per kilogram (mg/kg), gemcitabine 900 milligrams per meter square (mg/m2) on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.
Intervention: Ramucirumab
Ramucirumab + Gemcitabine + Docetaxel
Participants received intravenous (IV) infusions of ramucirumab 9 milligrams per kilogram (mg/kg), gemcitabine 900 milligrams per meter square (mg/m2) on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.
Intervention: Gemcitabine
Ramucirumab + Gemcitabine + Docetaxel
Participants received intravenous (IV) infusions of ramucirumab 9 milligrams per kilogram (mg/kg), gemcitabine 900 milligrams per meter square (mg/m2) on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.
Intervention: Docetaxel
Gemcitabine + Docetaxel
Participants received intravenous infusions of gemcitabine 900 mg/m2 on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.
Intervention: Gemcitabine
Gemcitabine + Docetaxel
Participants received intravenous infusions of gemcitabine 900 mg/m2 on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.
Intervention: Docetaxel
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Baseline to Objective Progression or Death Due to Any Cause (Up To 6.4 Months)
PFS is defined as the time from randomization until the first investigator-determined objective progression as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause in the absence of progressive disease. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment or date of randomization, whichever is later.
Secondary Outcomes
- Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)(Baseline through Measured Progressive Disease (Up To 6.4 Months))
- Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 4.13 Months))
- Complete Response (CR): Percentage of Participants Who Achieve CR(Baseline Up to 6.94 months)
- Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)(0.5 hours after the end of ramucirumab infusion on Day 1 of Cycle 1)
- PK: Minimum Serum Concentration of Ramucirumab (Cmin)(Prior to ramucirumab infusion on Day 8 of Cycle 1, Day 1 of Cycle 2 and Day 1 of Cycle 5)
- Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA)(Baseline Up to 6.94 months)