Clinical trial NCT04145700: CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Synovial Sarcoma
Official title: A Randomized, Open-Label Phase 1/2 Study Evaluating Ramucirumab in Pediatric Patients and Young Adults With Relapsed, Recurrent, or Refractory Synovial Sarcoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Synovial Sarcoma
Keywords: soft tissue sarcoma
adolescents and young adults (AYAs)
adolescent
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-10-31
Enrollment: 23
Sex: ALL
Minimum age (years): 12
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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) 1.1.
  * 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.
* 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 ramucirumab and 6 months following the last dose of docetaxel and gemcitabine in order to prevent pregnancy.

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 gemcitabine and docetaxel regimen. Participants who received combination as maintenance therapy, without progression, would be eligible.
* Participants with a known hypersensitivity to ramucirumab, gemcitabine, docetaxel, or agents formulated with Polysorbate 80.
* 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 symptomatic interstitial pneumonia or pulmonary fibrosis (or consistent findings of interstitial pneumonia/pulmonary fibrosis on imaging).
* Participants with central nervous system (CNS) involvement are ineligible.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Up To 6.4 Months)
Secondary outcomes:
measure: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline through Measured Progressive Disease (Up To 6.4 Months)
measure: Duration of Response (DoR)
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 4.13 Months)
measure: Complete Response (CR): Percentage of Participants Who Achieve CR
timeFrame: Baseline Up to 6.94 months
measure: Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)
timeFrame: 0.5 hours after the end of ramucirumab infusion on Day 1 of Cycle 1
measure: PK: Minimum Serum Concentration of Ramucirumab (Cmin)
timeFrame: Prior to ramucirumab infusion on Day 8 of Cycle 1, Day 1 of Cycle 2 and Day 1 of Cycle 5
measure: Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA)
timeFrame: Baseline Up to 6.94 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Childrens Hospital of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Childrens Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Orange
country: United States
facility: Childrens Hospital of Orange County
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hosp
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital Research Foundation
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Westmead
country: Australia
facility: The Sydney Children's Hospitals Network
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Bruxelles
country: Belgium
facility: UCL- Saint Luc
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Paris
country: France
facility: Institut Curie
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden-Württemberg
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
state: Lombardie
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Candiolo
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
state: Torino
city: Padova
country: Italy
facility: Azienda Ospedaliera Di Padova
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Manchester
country: United Kingdom
facility: The Christie
state: Greater Manchester
city: London
country: United Kingdom
facility: University College Hospital - London
city: London
country: United Kingdom
facility: Royal Marsden Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: