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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinosarcoma, Ovarian
• Intervention / Treatment: Drug: Galunisertib; Drug: Paclitaxel; Drug: Carboplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center, University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2017
• Primary Completion (Actual): July 28, 2021
• Study Completion (Anticipated): August 19, 2023

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 29, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Complex and Mixed; Sarcoma; Carcinosarcoma; Mixed Tumor, Mullerian; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: OU-SCC-EXIST-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No