Neoplasm Metastasis, Sarcoma, Ewing
Conditions
Brief summary
The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolomide) 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.
Interventions
DRUGAbemaciclib
Orally
DRUGIrinotecan
IV
DRUGTemozolomide
Orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 39 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Assessed by Blinded Independent Review Committee (BIRC) by Bayesian Analysis | From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months) | PFS was defined as the time from randomization until the first occurrence of documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, or death from any cause in absence of progressive disease, whichever came first. Progressive disease (PD) was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using Bayesian analysis and are reported as posterior mean along with its 80% credible interval. |
| PFS Assessed by BIRC by Frequentist Analysis | From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.36 months) | PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using frequentist analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Assessed by Investigator by Bayesian Analysis | From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months) | PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST v1.1 criteria, or date of randomization (whichever was later). Results were obtained using Bayesian analysis and are reported as posterior mean along with its 80% credible interval. |
| PFS Assessed by Investigator by Frequentist Analysis | From Date of Randomization until Disease Progression or Death Due to Any Cause (Up to 22.39 Months) | PFS was defined as the time from randomization until the first occurrence of documented disease progression per RECIST v1.1 criteria, or death from any cause in absence of progressive disease, whichever came first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. An event was considered when tumor progression or death occurred, with the event date being the earliest date of PD or death. Participants known to be alive and without tumor progression were censored at the date of their last adequate tumor assessment per RECIST 1.1 criteria, or date of randomization (whichever was later). Results were obtained using frequentist analysis. |
| Overall Survival (OS) | From Date of Randomization until Death Due to Any Cause (Up to 26.37 months) | OS was defined as the time from date of randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive. |
| Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) Assessed by BIRC | From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months) | ORR was defined as the number of participants who achieved the best overall response of complete response (CR) or partial response (PR) as per RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. |
| ORR: Percentage of Participants Who Achieved a CR or PR Assessed by Investigator | From Date of Randomization until Disease Progression, Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months) | ORR was defined as the number of participants who achieved the best overall response of CR or PR as per RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. |
| Duration of Response (DoR) Assessed by BIRC | From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 10.7 Months) | DoR was defined as the time from the date that measurement criteria for CR or PR (whichever was first recorded) were first met until the first date that recurrent disease or documented disease progression was observed per RECIST v1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. DoR was calculated for participants with only PR or CR. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants with an observed CR or PR, no confirmed disease progression per RECIST v1.1 criteria, and no death due to any cause were censored at the time of the last adequate post-baseline scan. |
| DoR Assessed by Investigator | From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up to 12.7 Months) | DoR was defined as the time from the date that measurement criteria for CR or PR (whichever was first recorded) were first met until the first date that recurrent disease or documented disease progression was observed, per RECIST v1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. DoR was calculated for participants with only PR or CR. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants with an observed CR or PR, no confirmed disease progression per RECIST v1.1 criteria, and no death due to any cause were censored at the time of the last adequate post-baseline scan. |
| Percentage of Participants With a Best Overall Response of CR, PR, Stable Disease (SD) or Non-CR/Non-PD: Disease Control Rate (DCR) Assessed by BIRC | From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.36 Months) | Disease control rate (DCR) was the percentage of participants with a best overall response of CR, PR, SD or Non-CR/Non-PD as defined by RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Non-CR/Non-PD was defined as persistence of one or more non-target lesions and/or maintained tumor marker levels, but without sufficient progression to be considered PD and without complete disappearance to be CR. |
| Percentage of Participants With a Best Overall Response of CR, PR or SD: DCR Assessed by Investigator | From Date of Randomization until Disease Progression, or Death Due to Any Cause, Concomitant Radiotherapy/Surgery, or Start of New Anti-Cancer Therapy (Up to 22.39 Months) | DCR was the percentage of participants with a best overall response of CR, PR, or SD as defined by RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease for target lesions, no progression of non-target lesions, and no appearance of new lesions. |
| Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of Abemaciclib | Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1; End of irinotecan infusion on Cycle 2 Day 1 and Cycle 4 Day 1 | PK: Cmin of Abemaciclib were reported. |
| Abemaciclib Product Acceptability | Day 1 of Cycle 1 through Cycle 3 (21-day cycles) | Participants were evaluated for abemaciclib acceptability by asking a question - " Was it easy or difficult for the study participant to swallow the abemaciclib today?" Participants or their caregivers or both could respond using the following possible answers: "Very difficult", "difficult", "neither easy nor difficult", "easy", or "very easy". Acceptability was assessed for formulations: tablets, oral granules, and dispersed tablets. |
Countries
Australia, France, Germany, Italy, Japan, Spain, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 17.1 Years STANDARD_DEVIATION 6.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment Australia | 1 Participants |
| Region of Enrollment France | 7 Participants |
| Region of Enrollment Germany | 1 Participants |
| Region of Enrollment Italy | 5 Participants |
| Region of Enrollment Japan | 9 Participants |
| Region of Enrollment Spain | 7 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 30 | 8 / 16 |
| other Total, other adverse events | 30 / 30 | 15 / 15 |
| serious Total, serious adverse events | 12 / 30 | 5 / 15 |
Outcome results
None listed