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CompletedNCT03206177Updated Aug 7, 2024Results posted

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

A Phase 1 interventional study of Galunisertib and Paclitaxel in Carcinosarcoma, Ovarian, sponsored by University of Oklahoma. Completed at 1 site in United States. Open to female participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2024-08-07.

Sponsored by University of Oklahoma · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
26
Allocation
Not applicable
Ages
18 Years to 99 Years
Sex
Female
01

Study 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.

Read the 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.

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Conditions studied

  • Carcinosarcoma, Ovarian
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Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
Female
Accepts 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

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.
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Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Paclitaxel/Carboplatin + 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

    Drug: Galunisertib · Drug: Paclitaxel · Drug: Carboplatin

Interventions

  • DrugGalunisertib

    Galunisertib 150mg po BID day 4-17

  • 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)

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What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. Median Overall Survival (Months)

    Overall survival defined as time from study entry to death

    Time frame: through study completion, an average of 3 years

  3. 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

06

Results

Posted Aug 7, 2024

Participant flow

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.

Participant flow — Overall Study
MilestonePaclitaxel/Carboplatin + Galunisertib
Started24
Completed23
Not completed1
Withdrew: Withdrawal by subject1

Outcome measures

PrimaryProportion 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
Reported as:
Number · proportion of patients
Proportion of Patients With Completion of 4 Cycles of CT + GB
proportion of patientsPaclitaxel/Carboplatin + Galunisertib
Proportion of Patients With Completion of 4 Cycles of CT + GB0.7826 (0.5961 to 0.9102)
SecondaryMedian 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
Reported as:
Median · months
Median Progression Free Survival (Months)
monthsPaclitaxel/Carboplatin + Galunisertib
Median Progression Free Survival (Months)6.55 (5.42 to 10.81)
SecondaryMedian Overall Survival (Months)

Overall survival defined as time from study entry to death

Time frame:
through study completion, an average of 3 years
Reported as:
Median · months
Median Overall Survival (Months)
monthsPaclitaxel/Carboplatin + Galunisertib
Median Overall Survival (Months)18.91 (10.81 to NA)
SecondaryObjective 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
Reported as:
Number · proportion of patients with CR/PR
Objective Response
proportion of patients with CR/PRPaclitaxel/Carboplatin + Galunisertib
Objective Response0.33 (0.15 to 0.57)

Adverse events

Collected over Within 4 years of study entry. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Paclitaxel/Carboplatin + Galunisertib1/24 (4.2%)11/24 (45.8%)23/24 (95.8%)
Most frequent serious events
Showing 10 of 18
Most frequent serious events
EventPaclitaxel/Carboplatin + Galunisertib
ARTRIAL FIBRILLATIONCardiac disorders1/24
SMALL BOWEL OBSTRUCTIONGastrointestinal disorders1/24
VOMITINGGastrointestinal disorders1/24
DEATHGeneral disorders1/24
FEVERGeneral disorders1/24
NEUTROPENIC FEVERGeneral disorders1/24
PULMONARY INFECTIONInfections and infestations1/24
URINARY TRACT INFECTIONInfections and infestations1/24
DRUG INDUCED LIVER INJURYInjury, poisoning and procedural complications1/24
LEFT LEG FRACTUREMusculoskeletal and connective tissue disorders1/24
Most frequent other events
Showing 10 of 29
Most frequent other events
EventPaclitaxel/Carboplatin + Galunisertib
NEUROPATHYNervous system disorders13/24
FATIGUEGeneral disorders11/24
NEUTROPENIABlood and lymphatic system disorders10/24
NAUSEAGastrointestinal disorders9/24
ARTHRALGIAMusculoskeletal and connective tissue disorders8/24
URINARY TRACT INFECTIONInfections and infestations6/24
RASHSkin and subcutaneous tissue disorders5/24
ANEMIABlood and lymphatic system disorders4/24
THROMBOCYTOPENIABlood and lymphatic system disorders4/24
CONSTIPATIONGastrointestinal disorders4/24

Baseline characteristics

Patients who enrolled in study

Age, Continuous
Age, Continuous(years)Paclitaxel/Carboplatin + Galunisertib
Mean68.96 ± 10.16
Sex: Female, Male
Sex: Female, Male(Participants)Paclitaxel/Carboplatin + Galunisertib
Female24
Male0
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Paclitaxel/Carboplatin + Galunisertib
Hispanic or Latino1
Not Hispanic or Latino23
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Paclitaxel/Carboplatin + Galunisertib
American Indian or Alaska Native1
Asian2
Native Hawaiian or Other Pacific Islander0
Black or African American3
White17
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Paclitaxel/Carboplatin + Galunisertib
United States24
BMI
BMI(kg/m^2)Paclitaxel/Carboplatin + Galunisertib
Mean27.08 ± 8.40
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Study locations

1 site
  • Stephenson Cancer Center, University of Oklahoma Health Sciences Center
    Oklahoma City, Oklahoma 73104, United States
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References and documents

Study documents

  • Study protocol · Apr 22, 2021
  • Statistical analysis plan · Jul 13, 2022
  • Informed consent form · May 10, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT03206177
Lead sponsor
University of Oklahoma
Collaborators
Eli Lilly and Company
Responsible party
Sponsor
First posted
Jul 2, 2017
Start date
Aug 23, 2017
Primary completion
Jul 28, 2021
Completion
Feb 13, 2024
Results posted
Aug 7, 2024
Last update
Aug 7, 2024

Study contacts

Kathleen Moore, MD
principal investigator · Obstetrics and Gynecology

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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