A Randomized, Open-Label Phase 1/2 Study Evaluating Ramucirumab in Pediatric Patients and Young Adults With Relapsed, Recurrent, or Refractory Desmoplastic Small Round Cell Tumor
Overview
- Phase
- Phase 1
- Intervention
- Ramucirumab
- Conditions
- Desmoplastic Small Round Cell Tumor
- Sponsor
- Eli Lilly and Company
- Enrollment
- 30
- Locations
- 22
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Active, not recruiting
- Last Updated
- 4 months 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 desmoplastic small round cell tumor (DSRCT) 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 DSRCT.
- •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). This prior treatment must include approved therapies for which they are eligible, unless the participant 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 + Cyclophosphamide + Vinorelbine
Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Ramucirumab administered intravenously at a dose of 12 milligrams per kilogram (mg/kg) as a one-hour infusion on days 1 and 15. * Cyclophosphamide administered orally at 25 milligrams per meter square (mg/m2) daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.
Intervention: Ramucirumab
Ramucirumab + Cyclophosphamide + Vinorelbine
Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Ramucirumab administered intravenously at a dose of 12 milligrams per kilogram (mg/kg) as a one-hour infusion on days 1 and 15. * Cyclophosphamide administered orally at 25 milligrams per meter square (mg/m2) daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.
Intervention: Cyclophosphamide
Ramucirumab + Cyclophosphamide + Vinorelbine
Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Ramucirumab administered intravenously at a dose of 12 milligrams per kilogram (mg/kg) as a one-hour infusion on days 1 and 15. * Cyclophosphamide administered orally at 25 milligrams per meter square (mg/m2) daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.
Intervention: Vinorelbine
Cyclophosphamide + Vinorelbine
Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Cyclophosphamide administered orally at 25 mg/m² daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.
Intervention: Cyclophosphamide
Cyclophosphamide + Vinorelbine
Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Cyclophosphamide administered orally at 25 mg/m² daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.
Intervention: Vinorelbine
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: Randomization to Objective Progression or Death Due to Any Cause (Up To 23 Months)
PFS was defined as the time from randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause in the absence of disease progression. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.Participants known to be alive and without disease progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever is later). The posterior median and 98% credible interval were estimated using Bayesian analysis. Data are presented as the posterior median with 98% credible interval.
Secondary Outcomes
- Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR)(Randomization until measured progressive disease (Up To 23 Months))
- Duration of Response (DoR)(Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 23 Months))
- Complete Response (CR) : Percentage of Participants Who Achieved a CR(Randomization until measured progressive disease (Up To 23 Months))
- Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)(End of ramucirumab infusion on Day 1 of Cycle 1)
- PK: Minimum Serum Concentration of Ramucirumab (Cmin)(Prior to ramucirumab infusion on - Day 15 of Cycle 1 and Day 1 of Cycles 2, 4, 7, and 10)
- Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA)(Baseline Up to 23 months)