Carcinosarcoma, Ovarian
Conditions
Brief summary
This is a Phase 1 B feasibility trial with Galunsertib, a TGFβ inhibitor, in combination with carboplatin/paclitaxel in patients with newly diagnosed, persistent or recurrent carcinosarcoma of the uterus or ovary. The objective of the study is to determine whether this drug combination is safe for this patient population and to see if it is effective in shrinking cancers, keeping them from growing or helping patients live longer.
Detailed description
Patients who consent to this study will receive treatment for four 28 day cycles unless they are unable to continue study treatment due to toxicity or disease progression. Paclitaxel and carboplatin will be given intravenously on day 1 of each cycle and galunisertib in pill form on days 4-17. No medicine will be given on days 17-28 of each cycle. Patients may have the option of continuing treatment with the study drug if they complete the 4 cycles the study requires. Subjects will receive tests and procedures that are part of regular cancer care as well as those required for the purposes of the study. Blood samples will be taken to monitor the level of study drug in the blood. Patients will have the option of allowing blood and tumor samples to be used for future research.
Interventions
DRUGPaclitaxel
IV Day 1: Paclitaxel 175 mg/m2 over 3 hours
DRUGCarboplatin
IV Day 1: Carboplatin AUC 6\* over 1 hour (or 5\* if prior radiation therapy)
DRUGGalunisertib
Galunisertib 150mg po BID day 4-17
Sponsors
Eli Lilly and Company
University of Oklahoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Women ≥ 18 years old with a diagnosis of primary, recurrent or progressive uterine, ovarian, fallopian tube or peritoneal carcinosarcoma, for whom treatment with combination paclitaxel and carboplatin is recommended. 2. Written informed consent/assent prior to any study-specific procedures 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 4. Tissue available for translational study (paraffin block or new biopsy) . 5. Adequate bone marrow, renal, and hepatic function as defined per protocol. 6. No disease-modifying therapy, including investigational treatments, within 28 days prior to initiation of study treatment. 7. Ability to swallow tablets 8. For Women of child-bearing potential:Willingness to use a highly effective method of contraception during the study and for 6 months following the last dose of galunisertib. Negative beta human chorionic gonadotropin pregnancy test documented within 7 days prior to initiation of study drug. 9. Patient must have measurable disease before the treatment
Exclusion criteria
1. Planned radiotherapy during or after the study chemotherapy prior to disease progression. 2. Receipt of chemotherapy or radiation within 28 days of study treatment 3. Have had a major surgical procedure or a significant traumatic injury within 28 days prior to study treatment; Minor procedures such as biopsy within 7 days prior to study treatment are allowed. 4. Active infection that would preclude receipt of chemotherapy 5. Moderate or severe cardiovascular disease per protocol 6. Active pregnancy or lactation 7. Second primary malignancy for which treatment during the study period would be recommended if this cancer were not also present. 8. Prior malignancy requiring treatment within the last 3 years 9. Use of another investigational product or device within 4 weeks of study entry or during study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Completion of 4 Cycles of CT + GB | 2 years | Completion of 4 cycles of CT + GB- completion of a cycle will be defined as receiving both carboplatin/paclitaxel and taking ≥75% of the doses of GB for the cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (Months) | through study completion, an average of 3 years | Progression free survival is defined as time from when the patient is registered on the study until RECIST v1.1 documented disease progression as per the protocol or death. |
| Median Overall Survival (Months) | through study completion, an average of 3 years | Overall survival defined as time from study entry to death |
| Objective Response | within three years of study entry | Proportion of patients who had RECIST documented partial or complete response. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 10 mm when measured by CT and MRI; or ≥ 20 mm when measured by conventional techniques, including plain x-ray. Response was documented per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions. |
Countries
United States
Participant flow
Recruitment details
This single site study conducted at the University of Oklahoma Stephenson Cancer Center enrolled 26 participants between August 2017 and March 2021. The first participant was enrolled on August 23, 2017 and the last participant was enrolled on March 29, 2021.
Pre-assignment details
Of the 26 enrolled participants, 24 met inclusion criteria (2 participants were screen-fails) and were assigned to the study arm to receive treatment. Of the 24 participants that received treatment, 23 participants were evaluable based on the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel/Carboplatin + Galunisertib Galunisertib: Galunisertib 150mg po BID day 4-17
Paclitaxel: Paclitaxel 175 mg/m2 over 3 hours
Carboplatin: IV day 1 Carboplatin AUC 6\* over 1 hour (or 5\* if prior radiation therapy) | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Paclitaxel/Carboplatin + Galunisertib |
|---|---|
| Age, Continuous | 68.96 years STANDARD_DEVIATION 10.16 |
| BMI | 27.08 kg/m^2 STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 1 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 24 |
| other Total, other adverse events | 23 / 24 |
| serious Total, serious adverse events | 11 / 24 |
Outcome results
Primary
Proportion of Patients With Completion of 4 Cycles of CT + GB
Completion of 4 cycles of CT + GB- completion of a cycle will be defined as receiving both carboplatin/paclitaxel and taking ≥75% of the doses of GB for the cycle.
Time frame: 2 years
Population: Evaluable patients will be defined as patients who receive at least four cycles of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel/Carboplatin + Galunisertib | Proportion of Patients With Completion of 4 Cycles of CT + GB | 0.7826 proportion of patients |
Secondary
Median Overall Survival (Months)
Overall survival defined as time from study entry to death
Time frame: through study completion, an average of 3 years
Population: Patients who received at least four cycles of study drug
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel/Carboplatin + Galunisertib | Median Overall Survival (Months) | 18.91 months |
Secondary
Median Progression Free Survival (Months)
Progression free survival is defined as time from when the patient is registered on the study until RECIST v1.1 documented disease progression as per the protocol or death.
Time frame: through study completion, an average of 3 years
Population: Patients who received at least four cycles of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel/Carboplatin + Galunisertib | Median Progression Free Survival (Months) | 6.55 months |
Secondary
Objective Response
Proportion of patients who had RECIST documented partial or complete response. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 10 mm when measured by CT and MRI; or ≥ 20 mm when measured by conventional techniques, including plain x-ray. Response was documented per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions.
Time frame: within three years of study entry
Population: Patients who received four cycles of study drugs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paclitaxel/Carboplatin + Galunisertib | Objective Response | 0.33 proportion of patients with CR/PR |