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Paclitaxel, Carboplatin, and Galunisertib in Treating Patients with Newly Diagnosed, Persistent, or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Carcinosarcoma

Trial Status: Active

This phase Ib trial studies the side effects and how well paclitaxel, carboplatin, and galunisertib work in treating patients with uterine, ovarian, fallopian tube, or peritoneal carcinosarcoma that is newly diagnosed, does not go to remission despite treatment (persistent), or has come back (recurrent). Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Galunisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel, carboplatin, and galunisertib may work better in treating patients with uterine, ovarian, fallopian tube, or peritoneal carcinosarcoma.

Inclusion Criteria

  • Women 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
  • Absolute neutrophil count (ANC) >= 1500 cells/mcl
  • Platelets >= 100,000/mcl
  • Creatinine =< 2.0 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 times institutional normal
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels =< 2.5 x ULN
  • 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 with one of the following: * Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension * Major electrocardiography (ECG) abnormalities (e.g. Q-QS wave abnormalities, left ventricular hypertrophy, Wolff-Parkinson-White syndrome, complete bundle branch block, intraventricular block, atrial fibrillation, atrial flutter or major ST-T changes) not responding to medical treatments. Major abnormalities documented by echocardiogram (ECHO) with Doppler (for example, moderate or severe heart valve function defect) that is not stable for at least 6 months. Note: Left ventricular [LV] ejection fraction < 50% is allowed only if clinically stable for at least 6 months (evaluation based on the institutional lower limit of normal) * Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast)
  • 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

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: ACTIVE
Contact: Camille Gunderson
Phone: 405-271-8001

PRIMARY OBJECTIVE:

I. To determine the feasibility of delivering 4 cycles of carboplatin/paclitaxel (CT) in combination with galunisertib (GB) to patients with gynecologic carcinosarcoma.

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.

II. To determine the progression free survival (PFS) and overall survival (OS) of patients receiving combination CT + GB.

III. To ascertain the pharmacokinetic profile of GB when given in a combination regimen with CT.

EXPLORATORY/OCRRELATIVE OBJECTIVES:

I. To determine if H-score criteria (% of cells and intensity) of immunohistochemistry (IHC) nuclear phospho-smad2/3 levels after cycle 1 are associated with response to galunisertib therapy.

II. To evaluate the messenger ribonucleic acid (mRNA) expression level of epithelial-mesenchymal transition (EMT) markers along with the TGFbeta1 in the GB pre-treated and post-treated patient samples

OUTLINE:

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour on day 1, and galunisertib orally (PO) twice daily (BID) on days 4-17. Patients may receive docetaxel IV on day 1 if they are intolerant or have an allergic reaction to paclitaxel. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years from date of registration.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Oklahoma Health Sciences Center

Principal Investigator
Camille Gunderson

  • Primary ID OU-SCC-EXIST-001
  • Secondary IDs NCI-2018-03789
  • Clinicaltrials.gov ID NCT03206177