Clinical trial NCT05440786: CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sarcoma, Ewing
Neoplasm Metastasis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2022-07-01
Enrollment: 45
Sex: ALL
Minimum age (years): 1
Maximum age (years): 39
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolamide) 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.


Eligibility criteria: 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
* Refractory disease or confirmed radiological progression or recurrence following first or later line of treatment of Ewing's sarcoma or Ewing's sarcoma-like tumor

  -- 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 C) 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 and/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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline to objective progression or death due to any cause (estimated up to 11 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline to date of death due to any cause (estimated up to 45 months)
measure: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR
timeFrame: Baseline to measured progressive disease (estimated up to 11 months)
measure: Duration of Response (DoR)
timeFrame: 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)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to measured progressive disease (estimated up to 11 months)
measure: PFS
timeFrame: Baseline to objective progression or death due to any cause (estimated up to 11 months)
measure: Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib
timeFrame: Cycle 3, Day 1 (21 day cycles)
measure: Abemaciclib Product Acceptability
timeFrame: Day 1 of Cycles 1 through 3 (21 day cycles)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: The Regents of the University of California - Los Angeles (UCLA Pediatrics)
state: California
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
state: Aquitaine
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden-Württemberg
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
state: Lazio
city: Bologna
country: Italy
facility: IRCCS Istituto Ortopedico Rizzoli
city: Kobe
country: Japan
facility: Hyogo Prefectural Kobe Children's Hospital
state: Hyogo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
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 Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: