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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Feasibility IB Trial of Paclitaxel/Carboplatin + Galunisertib (a Small Molecule Inhibitor of the Kinase Domain of Type 1 TGF-B Receptor) in Patients With Newly Diagnosed, Persistent or Recurrent Carcinosarcoma of the Uterus or Ovary

Conditions
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Carcinosarcoma, Ovarian

Intervention / Treatment
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* Drug: Galunisertib
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paclitaxel/Carboplatin + Galunisertib<br> | Drug: Galunisertib<br>* Galunisertib 150mg po BID day 4-17.)<br>Drug: Paclitaxel<br>* Paclitaxel 175 mg/m2 over 3 hours<br>Drug: Carboplatin<br>* IV day 1 Carboplatin AUC 6* over 1 hour (or 5* if no prior radiation therapy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with completion of 4 cycles of CT + GB | To determine the feasibility of delivering 4 cycles of carboplatin/paclitaxel (CT) in combination with galunisertib (GB) to patients with gynecologic carcinosarcoma | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events | To determine the frequency and severity of adverse events as assessed by the CTCAE v4 | 2 years | 
| Median progression free survival (months) | To determine the PFS of patients receiving drug combination | through study completion, an average of 3 years | 
| Mean (SD) of GB serum concentration levels on day 4, 8 and 29 (cycle 2 day 1) | Galunisertib serum concentration levels will be tested | 2 months | 
| Median overall survival (months) | To determine the overall survival of patients receiving drug combination | through study completion, an average of 3 years |