Clinical Trials /

CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Desmoplastic Small Round Cell Tumor

NCT04145349

Description:

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 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.

Related Conditions:
  • Desmoplastic Small Round Cell Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CAMFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Desmoplastic Small Round Cell Tumor
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17305
  • SECONDARY ID: J1S-MC-JV01
  • SECONDARY ID: 2018-004242-42
  • NCT ID: NCT04145349

Conditions

  • Desmoplastic Small Round Cell Tumor

Interventions

DrugSynonymsArms
RamucirumabLY3009806Ramucirumab + Cyclophosphamide + Vinorelbine
CyclophosphamideRamucirumab + Cyclophosphamide + Vinorelbine
VinorelbineRamucirumab + Cyclophosphamide + Vinorelbine

Purpose

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 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.

Trial Arms

NameTypeDescriptionInterventions
Ramucirumab + Cyclophosphamide + VinorelbineExperimentalRamucirumab given intravenously (IV), Cyclophosphamide given orally and vinorelbine given IV.
  • Ramucirumab
  • Cyclophosphamide
  • Vinorelbine
Cyclophosphamide + VinorelbineActive ComparatorCyclophosphamide given orally and vinorelbine given IV.
  • Cyclophosphamide
  • Vinorelbine

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) 1.1.

               -  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.

          -  Adequate hematologic function, as defined as:

               -  Absolute neutrophil count (ANC): ≥750/microliters (µL) granulocyte-colony
                  stimulating factor (G-CSF) permitted up to 48 hours prior. Participants with
                  documented history of benign ethnic neutropenia or other conditions could be
                  considered with a lower ANC after discussion with and approval from the Lilly
                  clinical research physician or scientist.

               -  Platelets: ≥75,000/cubic millimeters. Platelet transfusion permitted up to 72
                  hours prior.

               -  Hemoglobin: ≥8 grams per deciliter (g/dL) (≥80 g/liter). Transfusions to increase
                  the participant's hemoglobin level to at least 8 g/dL are permitted; however,
                  study treatment must not begin until 7 days after the transfusion, and complete
                  blood count criteria for eligibility are confirmed within 24 hr of first study
                  dose.

          -  Adequate renal function, as defined as:

               -  Creatinine clearance or radioscope glomerular filtration rate (GFR) ≥60
                  milliliters/minute/meters squared OR serum creatinine meeting the following
                  parameters:

                    -  for participants ≥18 years of age serum creatinine ≤1.5×upper limit of
                       normal (ULN);

                    -  for participants <18 years of age, serum creatinine based on age/gender as
                       follows: Age 1 to <2 years maximum serum creatinine 0.6, Age 2 to <6 years
                       maximum serum creatinine 0.8, Age 6 to <10 years maximum serum creatinine
                       1.0, Age 10 to <13 years maximum serum creatinine 1.2, Age 13 to <16 years
                       maximum serum creatinine 1.5 for males and 1.4 for females, Age 16 to <18
                       years maximum serum creatinine 1.7 for males and 1.4 for females.

               -  Urine protein meeting the following parameters:

                    -  for participants ≥18 years of age: <2+ on dipstick or routine urinalysis. If
                       urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour
                       urine must be collected and must demonstrate <2 grams of protein in 24 hours
                       to allow participation in the study.

                    -  for participants <18 years of age: ≤30 milligrams per deciliter urine
                       analysis or <2+ on dipstick. If urine dipstick or routine analysis indicates
                       proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate
                       <1 g of protein in 24 hours to allow participation in the study.

          -  Adequate liver function:

               -  Total bilirubin: ≤1.5×ULN. Except participants with document history of Gilbert
                  Syndrome who must have a total bilirubin level of <3.0×ULN.

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): ≤2.5×ULN OR
                  ≤5.0×ULN if the liver has tumor involvement.

          -  The participant has an adequate coagulation function as defined by International
             Normalized Ratio ≤1.5 or prothrombin time ≤1.5×ULN, and partial thromboplastin time
             ≤1.5×ULN if not receiving anticoagulation therapy. For participants receiving
             anticoagulants, exceptions to these coagulation parameters are allowed if they are
             within the intended or expected range for their therapeutic use. Participants must
             have no history of clinically significant active bleeding (defined as within 14 days
             of first dose of study drug) or pathological condition that carries a high risk of
             bleeding (for example, tumor involving major vessels or known esophageal varices).

          -  The participant has adequate hematologic and organ function ≤1 week (7 days) prior to
             first dose of study drug.

          -  Female participants of childbearing potential must have a negative urine or serum
             pregnancy test within 7 days prior to randomization. Male and female participants must
             agree to use highly effective contraception for the duration of the study and up to 3
             months following the last dose of study medication.

        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:

               -  Participants with evidence of active bleeding or a history of significant (≥Grade
                  3) bleeding event within 3 months prior to enrollment are not eligible.

               -  Participants with a bleeding diathesis or vasculitis are not eligible.

               -  Participants with known or prior history in the prior 3 months of esophageal
                  varices are not eligible.

               -  Participants with a history of deep vein thrombosis requiring medical
                  intervention (including pulmonary embolism) within 3 months prior to study
                  enrollment are not eligible.

               -  Participants with a history of hemoptysis or other signs of pulmonary hemorrhage
                  within 3 months prior to study enrollment are not eligible.

          -  Cardiac:

               -  Participants with a history of central nervous system (CNS) arterial/venous
                  thromboembolic events (VTEs) including transient ischemic attack (TIA) or
                  cerebrovascular accident (CVA) within 6 months prior to study enrollment are not
                  eligible.

               -  Participants with myocardial infarction or unstable angina within the prior 6
                  months.

               -  Participants with New York Heart Association Grade 2 or greater congestive heart
                  failure (CHF).

               -  Participants with serious and inadequately controlled cardiac arrhythmia.

               -  Participants with significant vascular disease (eg, aortic aneurysm, history of
                  aortic dissection).

               -  Participants with clinically significant peripheral vascular disease.

          -  Participants who have a history of fistula, gastrointestinal (GI) ulcer or
             perforation, or intra-abdominal abscess within 3 months of study enrollment are not
             eligible.

          -  Participants with a history of hypertensive crisis or hypertensive encephalopathy
             within 6 months of study enrollment are not eligible.

          -  Participants who have non-healing wound, unhealed or incompletely healed fracture, or
             a compound (open) bone fracture at the time of enrollment are not eligible.

          -  Participants previously treated and progressed on combination cyclophosphamide and
             vinorelbine regimen. Participants who received combination as maintenance therapy,
             without progression, would be eligible.

          -  Participants with a known hypersensitivity to ramucirumab, cyclophosphamide,
             vinorelbine or any of the excipients of the medicinal products.

          -  Hepatic impairment:

               -  Severe liver cirrhosis Child-Pugh Class B (or worse).

               -  Cirrhosis with a history of hepatic encephalopathy.

               -  Clinically meaningful ascites resulting from cirrhosis and requiring ongoing
                  treatment with diuretics and/or paracentesis.

               -  History of hepatorenal syndrome.

          -  The participant has a bowel obstruction, history or presence of inflammatory
             enteropathy or extensive intestinal resection (eg, hemicolectomy or extensive small
             intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or
             chronic diarrhea.

          -  The participant has a urinary outflow obstruction.

          -  The participant has Grade 2 hematuria or non-infectious cystitis at the time of
             screening.

          -  Participants with central nervous system (CNS) involvement are ineligible.
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)
Safety Issue:
Description:PFS

Secondary Outcome Measures

Measure:Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
Time Frame:Baseline through Measured Progressive Disease (Estimated up to 12 Months)
Safety Issue:
Description:ORR
Measure:Duration of Response (DoR)
Time Frame:Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 12 Months)
Safety Issue:
Description:DoR
Measure:Complete Response (CR): Percentage of Participants Who Achieve CR
Time Frame:Baseline to date of CR (Estimated up to 12 Months)
Safety Issue:
Description:CR
Measure:Pharmacokinetics (PK): Maximum Concentration (Cmax)
Time Frame:Cycle 1 through Cycle 10 (28 Day Cycles)
Safety Issue:
Description:PK: Cmax
Measure:PK: Minimum Concentration (Cmin)
Time Frame:Cycle 1 through Cycle 10 (28 Day Cycles)
Safety Issue:
Description:PK: Cmin
Measure:Number of Participants with Anti-Ramucirumab Antibodies
Time Frame:Baseline through End of Study (Estimated up to 12 Months)
Safety Issue:
Description:Number of Participants with Anti-Ramucirumab Antibodies

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • soft tissue sarcoma
  • adolescents and young adults (AYAs)
  • adolescent

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