Sarcoma, Sarcoma Metastatic
Conditions
Brief summary
This phase II trial studies how well trabectedin and olaparib work in treating patients with sarcoma that cannot be removed by surgery or has spread to other places in the body. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing cells, stopping them from dividing or stopping them from spreading. Olaparib may stop the growth of tumor cells by blocking pathways responsible for repairing damaged cells. Giving trabectedin and olaparib may shrink or stop the tumor from growing.
Interventions
DRUGOlaparib
Olaparib taken by mouth twice daily
DRUGTrabectedin
Trabectedin administered intravenously (IV) every 21 days
Sponsors
Janssen Scientific Affairs, LLC
AstraZeneca
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Age ≥ 16 years * Advanced unresectable or metastatic sarcoma * Cohort 1: Leiomyosarcoma (LMS)/Liposarcoma (LPS) * Cohort 2: Other sarcoma histologies (excluding gastrointestinal stromal tumors) * Received at least 1 prior standard chemotherapy. For cohort 1 patients, this must have included a prior anthracycline. * Measurable disease by RECIST 1.1 * Adequate hematologic, renal, hepatic function * Adequate creatine phosphokinase * ECOG performance status ≤ 1 * Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal (LLN) * Women of childbearing potential and men must agree to use adequate contraception from signing informed consent to at least 6 months (females) and 5 months (men) after study drug treatment Key
Exclusion criteria
* Prior therapy with PARP inhibitor, including olaparib * Prior therapy with trabectedin * Additional active malignancy or treatment for alternative cancer (excluding non-melanoma skin cancer) requiring treatment within the past two years * Pregnant or breastfeeding women * Known hypersensitivity to trabectedin or olaparib * Other exclusions per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 2 years | Percentage of participants with complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, within each cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | At 6 months | Defined as the duration of time from start of treatment to time of progression. Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median and 6-month PFS will be estimated along with their 95% confidence intervals. |
| Overall Survival | At 2 years after enrollment | Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median, 1- and 2-year OS probability estimates will be estimated along with their 95% confidence intervals. |
| Incidence of Adverse Events | Up to 30 days after end of treatment, and average of 4.5 months | The frequency and rates of adverse events occurring in at least 5% of participants and rates of grade 3-5 adverse events will be tabulated by system organ class and preferred term using Common Terminology Criteria of Adverse Events (CTCAE), within each cohort. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Both cohorts received the same treatment:
* Cohort 1: Leiomyosarcoma and liposarcoma
* Cohort 2: Other bone or soft tissue sarcoma histologies Treatment consists of 21-day cycles for a maximum of 18 months. Olaparib: Olaparib taken by mouth twice daily Trabectedin: Trabectedin administered intravenously (IV) every 21 days | 16 |
| Cohort 2 Both cohorts received the same treatment:
* Cohort 1: Leiomyosarcoma and liposarcoma
* Cohort 2: Other bone or soft tissue sarcoma histologies Treatment consists of 21-day cycles for a maximum of 18 months. Olaparib: Olaparib taken by mouth twice daily Trabectedin: Trabectedin administered intravenously (IV) every 21 days | 13 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | discontinued due to toxicity | 1 | 0 |
| Overall Study | Noncompliance | 0 | 1 |
| Overall Study | Patient was deemed ineligible before starting study treatment | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 23 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 29 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 27 Participants | 12 Participants |
| Region of Enrollment United States | 16 participants | 29 participants | 13 participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 16 | 5 / 13 |
| other Total, other adverse events | 16 / 16 | 13 / 13 |
| serious Total, serious adverse events | 2 / 16 | 4 / 13 |
Outcome results
Primary
Overall Response Rate
Percentage of participants with complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, within each cohort.
Time frame: Up to 2 years
Population: one patient in cohort 2 was not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Overall Response Rate | 0 Participants |
| Cohort 2 | Overall Response Rate | 2 Participants |
Secondary
Incidence of Adverse Events
The frequency and rates of adverse events occurring in at least 5% of participants and rates of grade 3-5 adverse events will be tabulated by system organ class and preferred term using Common Terminology Criteria of Adverse Events (CTCAE), within each cohort.
Time frame: Up to 30 days after end of treatment, and average of 4.5 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Incidence of Adverse Events | Acute Kidney Injury- Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | Platelet count decreased- Grade 4 | 3 number of events |
| Cohort 1 | Incidence of Adverse Events | Alanine aminotransferase increased- Grade 3 | 1 number of events |
| Cohort 1 | Incidence of Adverse Events | Hypokalemia- Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | Anemia- Grade 3 | 5 number of events |
| Cohort 1 | Incidence of Adverse Events | Sepsis- Grade 3 | 1 number of events |
| Cohort 1 | Incidence of Adverse Events | Aspartate aminotransferase increased - Grade 3 | 1 number of events |
| Cohort 1 | Incidence of Adverse Events | Neutrophil count decreased- Grade 4 | 11 number of events |
| Cohort 1 | Incidence of Adverse Events | Blood bilirubin increased- Grade 3 | 1 number of events |
| Cohort 1 | Incidence of Adverse Events | Sinus tachycardia- Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | Bronchopulmonary hemorrhage - Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | Fever- Grade 3 | 1 number of events |
| Cohort 1 | Incidence of Adverse Events | Ejection fraction decreased- Grade 4 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | White blood cell decreased- Grade 3 | 11 number of events |
| Cohort 1 | Incidence of Adverse Events | Fatigue- Grade 3 | 2 number of events |
| Cohort 1 | Incidence of Adverse Events | Platelet count decreased- Grade 3 | 8 number of events |
| Cohort 1 | Incidence of Adverse Events | Lung Infection- Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | White blood cell decreased- Grade 4 | 4 number of events |
| Cohort 1 | Incidence of Adverse Events | Lymphocyte count decreased- Grade 3 | 0 number of events |
| Cohort 1 | Incidence of Adverse Events | Neutrophil count decreased- Grade 3 | 31 number of events |
| Cohort 1 | Incidence of Adverse Events | Myalgia- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Anemia- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Fever- Grade 3 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Myalgia- Grade 3 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Neutrophil count decreased- Grade 3 | 8 number of events |
| Cohort 2 | Incidence of Adverse Events | Neutrophil count decreased- Grade 4 | 9 number of events |
| Cohort 2 | Incidence of Adverse Events | Platelet count decreased- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Platelet count decreased- Grade 4 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Sepsis- Grade 3 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Sinus tachycardia- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | White blood cell decreased- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | White blood cell decreased- Grade 4 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Acute Kidney Injury- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Alanine aminotransferase increased- Grade 3 | 3 number of events |
| Cohort 2 | Incidence of Adverse Events | Fatigue- Grade 3 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Aspartate aminotransferase increased - Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Blood bilirubin increased- Grade 3 | 0 number of events |
| Cohort 2 | Incidence of Adverse Events | Bronchopulmonary hemorrhage - Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Ejection fraction decreased- Grade 4 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Hypokalemia- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Lung Infection- Grade 3 | 1 number of events |
| Cohort 2 | Incidence of Adverse Events | Lymphocyte count decreased- Grade 3 | 1 number of events |
Secondary
Overall Survival
Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median, 1- and 2-year OS probability estimates will be estimated along with their 95% confidence intervals.
Time frame: At 2 years after enrollment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Overall Survival | 1 year post enrollment | 0.52 probability estimates |
| Cohort 1 | Overall Survival | 2 year post enrollment | 0 probability estimates |
| Cohort 2 | Overall Survival | 1 year post enrollment | 0.48 probability estimates |
| Cohort 2 | Overall Survival | 2 year post enrollment | 0.12 probability estimates |
Secondary
Progression Free Survival
Defined as the duration of time from start of treatment to time of progression. Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. Median and 6-month PFS will be estimated along with their 95% confidence intervals.
Time frame: At 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression Free Survival | 4.1 months |
| Cohort 2 | Progression Free Survival | 3.8 months |
Secondary
Progression Free Survival
Defined as the duration of time from start of treatment to time of progression. Calculated by the Kaplan-Meier method with errors according to Peto, within each cohort. reported as survival probability estimates
Time frame: At 1 year after enrollment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Progression Free Survival | 8.9 percentage of patients |
| Cohort 2 | Progression Free Survival | 20.2 percentage of patients |