CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05440786

Collaborator

(none)

Enrollment

Locations

Arms

67.9

Anticipated Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy for Ewing's sarcoma that has come back or did not respond to treatment. This trial is part of the CAMPFIRE master protocol, which is a platform to speed development of new treatments for children and young adults with cancer. Your participation in this trial could last 11 months or longer, depending on how you and your tumor respond.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma, Ewing Neoplasm Metastasis	Drug: Abemaciclib Drug: Irinotecan Drug: Temozolomide	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Irinotecan and Temozolomide in Participants With Relapsed or Refractory Ewing's Sarcoma

Anticipated Study Start Date :

Jan 13, 2023

Anticipated Primary Completion Date :

Feb 10, 2027

Anticipated Study Completion Date :

Sep 10, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abemaciclib + Irinotecan +Temozolomide Abemaciclib given orally in combination with irinotecan given IV and temozolomide given orally.	Drug: Abemaciclib Orally Other Names: LY2835219 Drug: Irinotecan IV Drug: Temozolomide Orally
Experimental: Irinotecan +Temozolomide Irinotecan given IV and temozolomide orally.	Drug: Irinotecan IV Drug: Temozolomide Orally

Arm

Intervention/Treatment

Experimental: Abemaciclib + Irinotecan +Temozolomide

Abemaciclib given orally in combination with irinotecan given IV and temozolomide given orally.

Drug: Abemaciclib

Orally

Other Names:

LY2835219

Drug: Irinotecan

Drug: Temozolomide

Orally

Experimental: Irinotecan +Temozolomide

Irinotecan given IV and temozolomide orally.

Drug: Irinotecan

Drug: Temozolomide

Orally

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [Baseline to objective progression or death due to any cause (estimated up to 11 months)]
PFS determined by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

Secondary Outcome Measures

Overall Survival (OS) [Baseline to date of death due to any cause (estimated up to 45 months)]
OS
Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR [Baseline to measured progressive disease (estimated up to 11 months)]
ORR
Duration of Response (DoR) [Date of first evidence of CR or PR to date of disease recurrence, objective disease progression, or death due to any cause (estimated up to 11 months)]
DoR
Disease Control Rate (DCR) [Baseline to measured progressive disease (estimated up to 11 months)]
DCR
PFS [Baseline to objective progression or death due to any cause (estimated up to 11 months)]
PFS determined by investigator assessment using RECIST 1.1
Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib [Cycle 3, Day 1 (21 day cycles)]
PK: Cmin of Abemaciclib
Abemaciclib Product Acceptability [Day 1 of Cycles 1 through 3 (21 day cycles)]
Participants evaluated abemaciclib acceptability (palatability and ease of administration) using a 5-category questionnaire. Participants were asked to select one of the following to describe the acceptability of abemaciclib: Very difficult, difficult, neither easy nor difficult, easy, or very easy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 39 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of Ewing's sarcoma or Ewing's sarcoma-like tumor by institutional pathologist. The original pathological report is required. Repeat biopsy at progression is not required
Confirmed radiological progression or refractory disease

-- Must have one measurable or evaluable lesion per RECIST 1.1

Adequate performance status based on age
For participants less than (<)16 years of age, a Lansky score greater than or equal to (≥)50, or
For participants ≥16 years of age, a Karnofsky score ≥50
Participants must have discontinued all previous treatments for cancer or investigational agents ≥7 days after the last dose and must have recovered from the acute effects
Adequate hematologic and organ function less than or equal to (≤)14 days prior to Day 1 of Cycle 1:
Absolute neutrophil count ≥1000/microliter (µL)
Platelets ≥75,000/cubic millimeter (mm³)
Hemoglobin ≥8 grams per deciLiter (g/Dl) (≥100 grams per Liter [g/L])
Total bilirubin ≤1.5 times (×) upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN
Creatinine clearance or calculated glomerular filtration rate (GFR) ≥60 milliliters per minute per square meter (Ml/min/m²) or serum creatinine based on age/gender
Female participants of childbearing potential must have a negative urine or serum pregnancy test
Body weight ≥10 kilograms (kg)
Must be able to swallow and/or have a gastric/nasogastric tube

-- Participants in the European Union must be able to swallow intact capsules

Stable or decreasing dose of steroids at least 7 days prior to enrollment
Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment
Participants/caregivers are able and willing to make themselves available for the duration of the study and are willing to follow study procedures, including adherence to the pharmacokinetic (PK) sampling schedule

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 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

hepatitis.

Participants who have had allogeneic bone marrow or solid organ transplant
Surgery: Participants who have had, or are planning to have, the following invasive procedures:
Major surgical procedure, laparoscopic procedure, or significant traumatic injury within 28 days prior to enrollment
Surgical or other wounds must be adequately healed prior to enrollment
Female participants who are pregnant or breastfeeding
Have received any prior cyclin-dependent kinase (CDK) 4 and 6 inhibitor
Progression during prior treatment with irinotecan or temozolomide
Have a known intolerability or hypersensitivity to any of the study treatments or dacarbazine
Diagnosed and/or treated additional malignancy within 3 years prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	The Regents of the University of California - Los Angeles (UCLA Pediatrics)	Los Angeles	California	United States	90095-1752
3	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana	United States	46202
4	Washington University	Saint Louis	Missouri	United States	63110
5	Lifespan Cancer Institute	Providence	Rhode Island	United States	02906
6	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
7	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
8	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
9	Royal Children's Hospital	Melbourne	Victoria	Australia	3052
10	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux	Aquitaine	France	33076
11	Centre Leon Berard	Lyon	Rhône-Alpes	France	69373 CEDE
12	Universitaetsklinikum Freiburg	Freiburg	Baden-Württemberg	Germany	79106
13	Universitaetsklinikum Essen	Essen	Nordrhein-	Germany	45122
14	Charité Campus Virchow-Klinikum	Berlin		Germany	13353
15	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Lazio	Italy	00168
16	IRCCS Istituto Ortopedico Rizzoli	Bologna		Italy	40136
17	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
18	Kyushu University Hospital	Fukuoka		Japan	812-8582
19	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]	Spain	08035
20	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]	Spain	08035
21	Hospital Sant Joan de Déu	Esplugues de Llobregat	Barcelona [Barcelona]	Spain	08950
22	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalunya [Cataluña]	Spain	08041
23	Hospital General Universitario Gregorio Marañon	Madrid	Madrid, Comunidad De	Spain	28009
24	Hospital Infantil Universitario Niño Jesús	Madrid	Madrid, Comunidad De	Spain	28009
25	Hospital Universitario La Paz	Madrid	Madrid, Comunidad De	Spain	28046
26	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
27	Hospital Universitario Fundación Jiménez Díaz	Madrid		Spain	28040
28	Hospital Universitario La Paz	Madrid		Spain	28046
29	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
30	Hospital Universitari i Politecnic La Fe	València		Spain	46026