CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Synovial Sarcoma

Synovial Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04145700
• Other study ID #: 17306
• Secondary ID: J1S-MC-JV022018-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 4, 2020
• Est. completion date: February 23, 2023

Study information

• Verified date: August 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: February 23, 2023
• Est. primary completion date: February 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 29 Years

Eligibility

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.

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

Drug:
• Ramucirumab
Ramucirumab given IV
• Gemcitabine
Gemcitabine given IV
• Docetaxel
Docetaxel given IV

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	The Sydney Children's Hospitals Network	Westmead	New South Wales
Belgium	UCL- Saint Luc	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	Centre Leon Berard	Lyon	Rhône-Alpes
France	Institut Curie	Paris
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden-Württemberg
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Italy	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino
Italy	Istituto Nazionale dei Tumori	Milano	Lombardie
Italy	Azienda Ospedaliera Di Padova	Padova
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	Kyushu University Hospital	Fukuoka
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Prinses Maxima Centrum	Utrecht
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Canarias	La Laguna
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen Del Rocio	Sevilla	Andalucía
United Kingdom	Royal Marsden Hospital	London
United Kingdom	University College Hospital - London	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	The Christie	Manchester	Greater Manchester
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Childrens Hospital of Alabama	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hosp	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Hospital	Fort Worth	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Childrens Hospital of Los Angeles	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota Hospital	Minneapolis	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Childrens Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University Medical School	Saint Louis	Missouri
United States	Seattle Children's Hospital Research Foundation	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Italy,  Japan,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	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.	Baseline to Objective Progression or Death Due to Any Cause (Up To 6.4 Months)
Secondary	Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)	ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.	Baseline through Measured Progressive Disease (Up To 6.4 Months)
Secondary	Duration of Response (DoR)	DoR is defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective disease progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence.	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 4.13 Months)
Secondary	Complete Response (CR): Percentage of Participants Who Achieve CR	CR is a disappearance of all target and non-target lesions and normalization of tumor marker level.	Baseline Up to 6.94 months
Secondary	Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)	Cmax was the concentration of study drug in the blood after the dose is administered. It was measured post-dose and was summarized using descriptive statistics.	0.5 hours after the end of ramucirumab infusion on Day 1 of Cycle 1
Secondary	PK: Minimum Serum Concentration of Ramucirumab (Cmin)	Cmin was the concentration of study drug in the blood immediately before the next dose was administered. It was measured pre-dose at all visits and was summarized using descriptive statistics.	Prior to ramucirumab infusion on Day 8 of Cycle 1, Day 1 of Cycle 2 and Day 1 of Cycle 5
Secondary	Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA)	A TE-ADA evaluable participant is considered to be TE-ADA positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement (treatment-boosted). If baseline result is ADA Not Present, then the participant is TE ADA positive if there is at least one post baseline result of ADA Present with titer >= 20 (treatment-induced).	Baseline Up to 6.94 months

External Links

•   CAMPFIRE: A Study of Ramucirumab (LY3009806) in Children and Young Adults With Synovial Sarcoma