Paclitaxel/Carboplatin + Galunisertib for Patients With Carcinosarcoma of the Uterus or Ovary

Phase 1

Completed

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.

Recruitment & Eligibility

Inclusion Criteria

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.
Written informed consent/assent prior to any study-specific procedures
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Tissue available for translational study (paraffin block or new biopsy) .
Adequate bone marrow, renal, and hepatic function as defined per protocol.
No disease-modifying therapy, including investigational treatments, within 28 days prior to initiation of study treatment.
Ability to swallow tablets
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.
Patient must have measurable disease before the treatment

Exclusion Criteria

Planned radiotherapy during or after the study chemotherapy prior to disease progression.
Receipt of chemotherapy or radiation within 28 days of study treatment
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.
Active infection that would preclude receipt of chemotherapy
Moderate or severe cardiovascular disease per protocol
Active pregnancy or lactation
Second primary malignancy for which treatment during the study period would be recommended if this cancer were not also present.
Prior malignancy requiring treatment within the last 3 years
Use of another investigational product or device within 4 weeks of study entry or during study participation.

Arm && Interventions

Group	Intervention	Description
Paclitaxel/Carboplatin + Galunisertib	Paclitaxel	Patients will receive the following in every cycle (1 cycle=28days). * Paclitaxel - 175 mg/m2 over 3 hours via IV on Day 1 * Carboplatin - AUC 6\* (or AUC 5\) over 1 hour via IV on Day 1 Galunisertib - 150mg orally twice a day on Days 4-17
Paclitaxel/Carboplatin + Galunisertib	Galunisertib	Patients will receive the following in every cycle (1 cycle=28days). * Paclitaxel - 175 mg/m2 over 3 hours via IV on Day 1 * Carboplatin - AUC 6\* (or AUC 5\) over 1 hour via IV on Day 1 Galunisertib - 150mg orally twice a day on Days 4-17
Paclitaxel/Carboplatin + Galunisertib	Carboplatin	Patients will receive the following in every cycle (1 cycle=28days). * Paclitaxel - 175 mg/m2 over 3 hours via IV on Day 1 * Carboplatin - AUC 6\* (or AUC 5\) over 1 hour via IV on Day 1 Galunisertib - 150mg orally twice a day on Days 4-17

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Locations (1): Stephenson Cancer Center, University of Oklahoma Health Sciences Center
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Oklahoma City, Oklahoma, United States