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

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Suspended

CT.gov ID

NCT04145700

Collaborator

(none)

Enrollment

Locations

Arms

45.9

Anticipated Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Synovial Sarcoma	Drug: Ramucirumab Drug: Gemcitabine Drug: Docetaxel	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 4, 2020

Anticipated Primary Completion Date :

Jul 13, 2022

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ramucirumab + Gemcitabine + Docetaxel Ramucirumab, Gemcitabine and Docetaxel given intravenously (IV).	Drug: Ramucirumab Ramucirumab given IV Other Names: LY3009806 Drug: Gemcitabine Gemcitabine given IV Drug: Docetaxel Docetaxel given IV
Active Comparator: Gemcitabine + Docetaxel Gemcitabine and Docetaxel given IV.	Drug: Gemcitabine Gemcitabine given IV Drug: Docetaxel Docetaxel given IV

Arm

Intervention/Treatment

Experimental: Ramucirumab + Gemcitabine + Docetaxel

Ramucirumab, Gemcitabine and Docetaxel given intravenously (IV).

Drug: Ramucirumab

Ramucirumab given IV

Other Names:

LY3009806

Drug: Gemcitabine

Gemcitabine given IV

Drug: Docetaxel

Docetaxel given IV

Active Comparator: Gemcitabine + Docetaxel

Gemcitabine and Docetaxel given IV.

Drug: Gemcitabine

Gemcitabine given IV

Drug: Docetaxel

Docetaxel given IV

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [Baseline to Objective Progression or Death Due to Any Cause (Estimated up to 12 Months)]]
PFS

Secondary Outcome Measures

Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) [Baseline through Measured Progressive Disease (Estimated up to 12 Months)]
ORR
Duration of Response (DoR) [Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 12 Months)]
DoR
Complete Response (CR): Percentage of Participants Who Achieve CR [Baseline to date of CR (Estimated up to 12 Months)]
CR
Pharmacokinetics (PK): Maximum Concentration (Cmax) [Cycle 1 through Cycle 13 (21 Day Cycles)]
PK: Cmax
PK: Minimum Concentration (Cmin) [Cycle 1 through Cycle 13 (21 Day Cycles)]
PK: Cmin
Number of Participants with Anti-Ramucirumab Antibodies [Baseline through End of Study (Estimated up to 12 Months)]
Number of Participants with Anti-Ramucirumab Antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months to 29 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of Alabama	Birmingham	Alabama	United States	35233
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
3	Childrens Hospital of Los Angeles	Los Angeles	California	United States	90027
4	UCLA Medical Center	Los Angeles	California	United States	90095
5	Childrens Hospital of Orange County	Orange	California	United States	92868
6	Children's Hospital of Colorado	Aurora	Colorado	United States	80045
7	Children's National Medical Center	Washington	District of Columbia	United States	20010
8	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
9	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
10	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
11	Riley Hospital for Children	Indianapolis	Indiana	United States	46202-5225
12	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
13	C.S. Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
14	University of Minnesota Hospital	Minneapolis	Minnesota	United States	55455
15	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
16	Washington University Medical School	Saint Louis	Missouri	United States	63110
17	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
18	Nationwide Children's Hosp	Columbus	Ohio	United States	43205-2664
19	Oregon Health and Science University	Portland	Oregon	United States	97239
20	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
21	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
22	Children's Medical Center Dallas	Dallas	Texas	United States	75235
23	Cook Children's Hospital	Fort Worth	Texas	United States	76104-2724
24	Texas Children's Hospital	Houston	Texas	United States	77030
25	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
26	Seattle Children's Hospital Research Foundation	Seattle	Washington	United States	98105
27	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
28	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
29	The Sydney Children's Hospitals Network	Westmead	New South Wales	Australia	2145
30	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
31	Royal Children's Hospital	Parkville	Victoria	Australia	3052
32	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen	Belgium	9000
33	UCL- Saint Luc	Bruxelles		Belgium	1200
34	Centre Leon Berard	Lyon	Rhône-Alpes	France	69008
35	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux		France	33076
36	Institut Curie	Paris		France	75248
37	Universitaetsklinikum Freiburg	Freiburg	Baden-Württemberg	Germany	79106
38	Universitaetsklinikum Essen	Essen		Germany	45147
39	Universitaetsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
40	Istituto Nazionale dei Tumori	Milano	Lombardie	Italy	20133
41	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
42	Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia	Candiolo	Torino	Italy	10060
43	Azienda Ospedaliera Di Padova	Padova		Italy	35128
44	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
45	Kyushu University Hospital	Fukuoka		Japan	812-8582
46	Leids Universitair Medisch Centrum	Leiden		Netherlands	2333 ZT
47	Prinses Maxima Centrum	Utrecht		Netherlands	3584 CS
48	Hospital Universitario Virgen Del Rocio	Sevilla	Andalucía	Spain	41013
49	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08025
50	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
51	Hospital Universitario de Canarias	La Laguna		Spain
52	Hospital Universitario La Paz	Madrid		Spain	28046
53	The Christie	Manchester	Greater Manchester	United Kingdom	M20 4BX
54	University College Hospital - London	London		United Kingdom	NW1 2PG
55	Royal Marsden Hospital	London		United Kingdom	SW3 6JJ
56	Royal Manchester Children's Hospital	Manchester		United Kingdom	M139WL

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director: 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), Eli Lilly and Company