Pembro/Carbo/Taxol in Endometrial Cancer

Sponsor
Daniela Matei, MD (Other)
Overall Status
Completed
CT.gov ID
NCT02549209
Collaborator
Merck Sharp & Dohme LLC (Industry), Hoosier Cancer Research Network (Other)
46
6
1
53.7
7.7
0.1

Study Details

Study Description

Brief Summary

This is a single-arm, open-label, multi-center phase II study for subjects with measurable advanced or recurrent endometrial cancer using pembrolizumab in combination with carboplatin and paclitaxel chemotherapy. As this combination of agents has not been tested in this subject population, the first six subjects enrolled will constitute a safety run-in cohort.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OUTLINE: This is a multi-center study.

INVESTIGATIONAL TREATMENT:

To ensure the safety of this combination treatment, an initial safety run-in will be conducted for the first 6 subjects. This initial cohort of 6 subjects will be enrolled and treated with standard doses as described below. Based on toxicity analysis of the initial 6 subjects following completion of 18 weeks of treatment, it will be determined if an extended safety run-in period would be beneficial.

In the absence of receiving any prior therapy, eligible subjects will be treated as follows on D1 of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles:

  • Pembrolizumab 200mg will be administered as a 30-minute intravenous (IV) infusion every 3 weeks.

  • Paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion.

  • Carboplatin will be dosed at area under the curve (AUC) of 6 and given as an IV infusion in 250ml of D5W over 30 minutes.

Subjects who have had prior radiotherapy/platinum-based chemotherapy must initiate paclitaxel and carboplatin at the following reduced dose levels if they have had prior external radiotherapy involving the whole pelvis or abdomen or over 50% of their spine, and/or prior platinum-based chemotherapy for this, or any other cancer. Eligible subjects will be treated as follows on Day 1 (D1) of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles:

  • Pembrolizumab 200mg administered as a 30-minute intravenous (IV) infusion every 3 weeks.

  • Paclitaxel will be dosed at 135mg/m2 and be administered as a 3-hour continuous IV infusion.

  • Carboplatin will be dosed at an AUC of 5 and given as an IV infusion in 250ml of D5W over 30 minutes.

Subsequent doses of paclitaxel and carboplatin may be escalated to the higher doses as indicated above, provided these subjects do not exhibit hematologic or nonhematologic toxicity > Grade 1, except alopecia.

The following laboratory values must be obtained within 14 days prior to registration for protocol therapy:

Hematopoietic:
  • Hemoglobin (Hgb) > 9 g/dL (without transfusion or erythropoietin (EPO) dependency within 7 days of assessment)

  • Platelets > 100 K/mm3

  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3

Renal:
  • Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) ≤ 1.5 X institutional upper limits of normal (ULN) OR ≥60mL/min for subjects with creatinine levels > 1.5 x institutional ULN
Hepatic:
  • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

  • Aspartate aminotransferase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) < 2.5 x ULN OR ≤ 5 x ULN for subjects with liver metastases

  • Albumin ≥ 2.5 mg/dL

Coagulation (Blood Clotting) Tests:
  • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants

  • Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Masking Description:
Open-Label
Primary Purpose:
Treatment
Official Title:
Phase II Study of Pembrolizumab in Combination With Carboplatin and Paclitaxel for Advanced or Recurrent Endometrial Adenocarcinoma
Actual Study Start Date :
Aug 22, 2017
Actual Primary Completion Date :
Dec 12, 2019
Actual Study Completion Date :
Feb 10, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Investigational Treatment

Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5

Drug: Pembrolizumab
Pembrolizumab 200 mg will be administered every 3 weeks for all subjects
Other Names:
  • MK-3475
  • Keytruda®
  • Drug: Paclitaxel
    For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion.
    Other Names:
  • Taxol®
  • Drug: Carboplatin
    For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    Other Names:
  • Paraplatin®
  • Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rates (ORR) [From start of treatment Day 1 (D1) and assessed for a maximum of 18 months]

      Objective response rate(ORR) is defined as the percentage of subjects with a partial response or complete response according to immune-related RECIST criteria. Immune-Related Response Criteria: Complete Response(irCR): Disappearance of all lesions in two consecutive observations not less than 4 wk apart. Partial Reponse (irPR): decrease in tumor burden ≥50 %relative to baseline confirmed by a consecutive assessment at least 4 wk after first documentation Stable Disease (irSD): not meeting criteria for irCR or irPR, in absence of irPD

    Secondary Outcome Measures

    1. Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria [From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )]

      Proportion of subjects who experience ≥ Grade 3 toxicity regardless of relation according per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 criteria while receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Written informed consent and HIPAA authorization for release of personal health information prior to registration for protocol therapy.

    o NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

    • Age ≥ 18 years at the time of consent.

    • ECOG Performance Status of 0 or 1 within 28 days prior to registration for protocol therapy.

    • Histological evidence of newly diagnosed Stage III or IV or recurrent endometrial carcinoma who have had definitive surgery for endometrial cancer (at least hysterectomy and bilateral salpingo-oophorectomy). Pathologic documentation of the recurrence (i.e., biopsy) will be performed per standard of care, at the treating physician's discretion. If a subject with recurrence is undergoing a biopsy for clinical indications and is willing and able, an optional collection of 3 frozen tissue cores of the recurrence site is requested for correlative analysis.

    • Measurable disease according to RECIST v1.1 and obtained by imaging within 28 days prior to registration for protocol therapy. Disease in an irradiated field as the only site of measurable disease is acceptable only if there has been clear progression since completion of radiation treatment.

    • The subject must have recovered (≤ grade 1) from the acute toxic effects of prior therapy.

    • Prior treatment: Subjects may have received none or one platinum-based chemotherapy regimen and none or one non-platinum regimen. Subjects having received prior platinum-based chemotherapy must have a disease-free interval > 6 months (be platinum sensitive).

    • Prior therapy with hormones or biologic agents is allowed. These treatments must be discontinued at least 28 days prior to registration for protocol therapy.

    • The subject must have completed radiation therapy at least 28 days prior to registration for protocol therapy, provided that toxicity has resolved to ≤ grade 1.

    • NOTES: Subjects may have received prior radiation therapy for treatment of endometrial carcinoma. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Chemotherapy used for radiation sensitization is allowed. Chemotherapy used for radiation sensitization will not count as second chemotherapy regimen.

    • Palliative radiation given primarily for symptom relief, without the intent to treat or cure the patient's endometrial cancer is excluded from the above criteria. Treatment-directed radiation will be defined as more than 30 Gy of radiation.

    • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for at least 5 years.

    • Female subjects must be of non-childbearing potential. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥1 year.

    • Laboratory values must be obtained within 14 days prior to registration for protocol therapy. Note: Institutional/laboratory upper limit of normal (ULN)

    • Hemoglobin (Hgb) > 9 g/dL (without transfusion or EPO dependency within 7 days of assessment)

    • Platelets > 100 K/mm3

    • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3

    • Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) ≤ 1.5 X institutional ULN OR ≥60mL/min for subjects with creatinine levels > 1.5 x institutional ULN

    • Serum total bilirubin ≤ 1.5 ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

    • AST, ALT or alkaline phosphatase < 2.5 ULN OR ≤ 5 x ULN for subjects with liver metastases

    • Albumin ≥ 2.5 mg/dL

    • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants

    • Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

    Exclusion Criteria:
    • Subjects with carcinosarcoma.

    • Subjects who have a solitary central pelvic recurrence, which can be curatively resected.

    • Hypersensitivity to pembrolizumab or any of its excipients.

    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to registration for protocol therapy or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to registration for protocol therapy and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior registration for protocol therapy. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.

    • NOTE: Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.

    • Treatment with any investigational agent within 28 days prior to registration for protocol therapy.

    • Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

    • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

    • Has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration for protocol therapy. (Prednisone (or equivalent) < 10mg/ day is allowed).

    • Has a known history of active TB (Bacillus Tuberculosis).

    • Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis.

    • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

    • Evidence of interstitial lung disease.

    • Has an active infection requiring systemic therapy with the exception of an uncomplicated urinary tract infection.

    • Pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v4 criteria.

    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

    • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.

    • Has received a live vaccine within 30 days prior to registration for protocol therapy.

    o NOTE: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.

    • History of solid organ or stem cell transplant requiring immunosuppressive medications.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ironwood Cancer and Research Centers Mesa Arizona United States 85206
    2 Northwestern University, Robert H. Lurie Cancer Center Chicago Illinois United States 60611
    3 Northwestern Medicine Lake Forest Hospital Lake Forest Illinois United States 60045
    4 Indiana University Melvin and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    5 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    6 University of Minnesota Minneapolis Minnesota United States 55455

    Sponsors and Collaborators

    • Daniela Matei, MD
    • Merck Sharp & Dohme LLC
    • Hoosier Cancer Research Network

    Investigators

    • Study Chair: Daniela Matei, M.D., Big Ten Cancer Research Consortium

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Daniela Matei, MD, Sponsor-Investigator, Big Ten Cancer Research Consortium
    ClinicalTrials.gov Identifier:
    NCT02549209
    Other Study ID Numbers:
    • BTCRC GYN15-013
    First Posted:
    Sep 15, 2015
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Daniela Matei, MD, Sponsor-Investigator, Big Ten Cancer Research Consortium
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Investigational Treatment
    Arm/Group Description Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5 Pembrolizumab: Pembrolizumab 200 mg will be administered every 3 weeks for all subjects Paclitaxel: For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion. Carboplatin: For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    Period Title: Overall Study
    STARTED 46
    COMPLETED 46
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Investigational Treatment
    Arm/Group Description Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5 Pembrolizumab: Pembrolizumab 200 mg will be administered every 3 weeks for all subjects Paclitaxel: For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion. Carboplatin: For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    Overall Participants 46
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    66
    Sex: Female, Male (Count of Participants)
    Female
    46
    100%
    Male
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    2.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    3
    6.5%
    White
    39
    84.8%
    More than one race
    0
    0%
    Unknown or Not Reported
    3
    6.5%
    Region of Enrollment (participants) [Number]
    United States
    46
    100%
    Stage at Diagnosis (Count of Participants)
    IA
    13
    28.3%
    IB
    7
    15.2%
    II
    8
    17.4%
    IIIA
    4
    8.7%
    IIIC1
    3
    6.5%
    IIIC2
    3
    6.5%
    IVA
    2
    4.3%
    IVB
    6
    13%
    Diagnosis Type (Count of Participants)
    Primary
    12
    26.1%
    Recurrent
    34
    73.9%
    Tumor Grade (Count of Participants)
    1
    14
    30.4%
    2
    10
    21.7%
    3
    22
    47.8%
    Histology (Count of Participants)
    Clear Cell
    3
    6.5%
    Endometrioid
    27
    58.7%
    Mucinous
    0
    0%
    Other
    5
    10.9%
    Serous
    11
    23.9%
    Previous Treatment (participants) [Number]
    Carboplatin/paclitaxel
    19
    41.3%
    External beam radiotherapy
    23
    50%
    Brachytherapy
    14
    30.4%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rates (ORR)
    Description Objective response rate(ORR) is defined as the percentage of subjects with a partial response or complete response according to immune-related RECIST criteria. Immune-Related Response Criteria: Complete Response(irCR): Disappearance of all lesions in two consecutive observations not less than 4 wk apart. Partial Reponse (irPR): decrease in tumor burden ≥50 %relative to baseline confirmed by a consecutive assessment at least 4 wk after first documentation Stable Disease (irSD): not meeting criteria for irCR or irPR, in absence of irPD
    Time Frame From start of treatment Day 1 (D1) and assessed for a maximum of 18 months

    Outcome Measure Data

    Analysis Population Description
    Forty-three of the enrolled patients were evaluable for efficacy using the primary endpoint of ORR. Three patients received a single dose of therapy and were not evaluable for response due to transition to hospice care, a severe allergic reaction to therapy, or no further follow up.
    Arm/Group Title Investigational Treatment
    Arm/Group Description Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5 Pembrolizumab: Pembrolizumab 200 mg will be administered every 3 weeks for all subjects Paclitaxel: For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion. Carboplatin: For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    Measure Participants 43
    Number (95% Confidence Interval) [percentage of participants]
    74.4
    161.7%
    2. Secondary Outcome
    Title Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria
    Description Proportion of subjects who experience ≥ Grade 3 toxicity regardless of relation according per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 criteria while receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy
    Time Frame From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Investigational Treatment
    Arm/Group Description Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5 Pembrolizumab: Pembrolizumab 200 mg will be administered every 3 weeks for all subjects Paclitaxel: For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion. Carboplatin: For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    Measure Participants 46
    Number [proportion of participants]
    0.74
    1.6%

    Adverse Events

    Time Frame From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )
    Adverse Event Reporting Description CTCAE grades the severity of an adverse event from 1-5 where 1=least severe and 5=death.
    Arm/Group Title Investigational Treatment
    Arm/Group Description Subjects with no prior therapy: Pembrolizumab administered at 200 mg Paclitaxel administered at 175mg/m2 Carboplatin administered at an AUC of 6 Subjects with prior external beam radiation therapy (XRT) and/or platinum-based chemotherapy must initiate paclitaxel and carboplatin at a reduced dose: Pembrolizumab administered at 200 mg Paclitaxel administered at 135mg/m2 Carboplatin administered at an AUC of 5 Pembrolizumab: Pembrolizumab 200 mg will be administered every 3 weeks for all subjects Paclitaxel: For subjects with no prior therapy, paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. Subjects with prior XRT/platinum-based chemotherapy must initiate paclitaxel at 135mg/m2 and be administered as a 3-hour continuous IV infusion. Carboplatin: For subjects with no prior therapy, carboplatin will be dosed at an AUC of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects with prior XRT/platinum-based chemotherapy must initiate carboplatin at an AUC of 5 given as an IV infusion in 250ml of D5W over 30 minutes.
    All Cause Mortality
    Investigational Treatment
    Affected / at Risk (%) # Events
    Total 11/46 (23.9%)
    Serious Adverse Events
    Investigational Treatment
    Affected / at Risk (%) # Events
    Total 16/46 (34.8%)
    Blood and lymphatic system disorders
    ANEMIA 1/46 (2.2%) 1
    Ear and labyrinth disorders
    VESTIBULAR DISORDER 1/46 (2.2%) 1
    Endocrine disorders
    HYPERTHYROIDISM 1/46 (2.2%) 1
    Gastrointestinal disorders
    COLITIS 1/46 (2.2%) 1
    NAUSEA 1/46 (2.2%) 1
    VOMITING 1/46 (2.2%) 1
    General disorders
    FATIGUE 1/46 (2.2%) 1
    FEVER 3/46 (6.5%) 3
    Immune system disorders
    ANAPHYLAXIS 1/46 (2.2%) 3
    Infections and infestations
    INFECTIONS AND INFESTATIONS 1/46 (2.2%) 1
    UPPER RESPIRATORY INFECTION 1/46 (2.2%) 1
    Investigations
    NEUTROPHIL COUNT DECREASED 1/46 (2.2%) 1
    Metabolism and nutrition disorders
    DEHYDRATION 2/46 (4.3%) 2
    HYPOKALEMIA 2/46 (4.3%) 2
    Musculoskeletal and connective tissue disorders
    MUSCLE WEAKNESS LOWER LIMB 1/46 (2.2%) 1
    Nervous system disorders
    ATAXIA 1/46 (2.2%) 1
    SYNCOPE 2/46 (4.3%) 2
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 1/46 (2.2%) 1
    Respiratory, thoracic and mediastinal disorders
    DYSPNEA 1/46 (2.2%) 2
    Vascular disorders
    HEMATOMA 1/46 (2.2%) 1
    THROMBOEMBOLIC EVENT 1/46 (2.2%) 1
    Other (Not Including Serious) Adverse Events
    Investigational Treatment
    Affected / at Risk (%) # Events
    Total 46/46 (100%)
    Blood and lymphatic system disorders
    ANEMIA 36/46 (78.3%) 92
    BLOOD AND LYMPHATIC SYSTEM DISORDERS 5/46 (10.9%) 6
    FEBRILE NEUTROPENIA 1/46 (2.2%) 1
    Cardiac disorders
    CARDIAC DISORDERS 1/46 (2.2%) 1
    SINUS BRADYCARDIA 1/46 (2.2%) 1
    SINUS TACHYCARDIA 7/46 (15.2%) 11
    Congenital, familial and genetic disorders
    CONGENITAL, FAMILIAL AND GENETIC DISORDERS 1/46 (2.2%) 1
    Ear and labyrinth disorders
    EAR PAIN 1/46 (2.2%) 1
    TINNITUS 1/46 (2.2%) 1
    VERTIGO 1/46 (2.2%) 3
    Endocrine disorders
    ENDOCRINE DISORDERS 6/46 (13%) 7
    HYPERTHYROIDISM 5/46 (10.9%) 5
    HYPOTHYROIDISM 17/46 (37%) 20
    Eye disorders
    BLURRED VISION 4/46 (8.7%) 4
    CATARACT 1/46 (2.2%) 1
    EYE DISORDERS 3/46 (6.5%) 3
    RETINAL VASCULAR DISORDER 1/46 (2.2%) 1
    WATERING EYES 2/46 (4.3%) 2
    Gastrointestinal disorders
    ABDOMINAL DISTENSION 1/46 (2.2%) 2
    ABDOMINAL PAIN 15/46 (32.6%) 15
    ASCITES 1/46 (2.2%) 2
    BLOATING 2/46 (4.3%) 2
    COLITIS 1/46 (2.2%) 1
    COLONIC FISTULA 1/46 (2.2%) 1
    CONSTIPATION 17/46 (37%) 28
    DIARRHEA 22/46 (47.8%) 32
    DRY MOUTH 1/46 (2.2%) 1
    DYSPEPSIA 2/46 (4.3%) 2
    ESOPHAGITIS 1/46 (2.2%) 1
    FECAL INCONTINENCE 1/46 (2.2%) 1
    GASTROESOPHAGEAL REFLUX DISEASE 4/46 (8.7%) 4
    GASTROINTESTINAL DISORDERS 5/46 (10.9%) 5
    HEMORRHOIDS 2/46 (4.3%) 2
    MUCOSITIS ORAL 3/46 (6.5%) 5
    NAUSEA 24/46 (52.2%) 43
    RECTAL HEMORRHAGE 3/46 (6.5%) 3
    RECTAL MUCOSITIS 1/46 (2.2%) 2
    STOMACH PAIN 2/46 (4.3%) 2
    VOMITING 9/46 (19.6%) 11
    General disorders
    CHILLS 3/46 (6.5%) 4
    EDEMA LIMBS 15/46 (32.6%) 17
    EDEMA TRUNK 2/46 (4.3%) 2
    FATIGUE 27/46 (58.7%) 42
    FEVER 4/46 (8.7%) 4
    GAIT DISTURBANCE 1/46 (2.2%) 1
    GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 8/46 (17.4%) 17
    INFUSION RELATED REACTION 5/46 (10.9%) 7
    INFUSION SITE EXTRAVASATION 1/46 (2.2%) 1
    NON-CARDIAC CHEST PAIN 2/46 (4.3%) 2
    PAIN 3/46 (6.5%) 3
    Immune system disorders
    IMMUNE SYSTEM DISORDERS 1/46 (2.2%) 1
    Infections and infestations
    BRONCHIAL INFECTION 1/46 (2.2%) 1
    INFECTIONS AND INFESTATIONS 5/46 (10.9%) 5
    LIP INFECTION 1/46 (2.2%) 1
    LUNG INFECTION 1/46 (2.2%) 2
    PHARYNGITIS 1/46 (2.2%) 1
    SEPSIS 1/46 (2.2%) 1
    SINUSITIS 2/46 (4.3%) 3
    SKIN INFECTION 1/46 (2.2%) 2
    UPPER RESPIRATORY INFECTION 3/46 (6.5%) 3
    URINARY TRACT INFECTION 10/46 (21.7%) 13
    Injury, poisoning and procedural complications
    BRUISING 5/46 (10.9%) 6
    FALL 7/46 (15.2%) 8
    FRACTURE 1/46 (2.2%) 1
    INJURY, POISONING AND PROCEDURAL COMPLICATIONS 1/46 (2.2%) 1
    Investigations
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED 9/46 (19.6%) 13
    ALANINE AMINOTRANSFERASE INCREASED 7/46 (15.2%) 8
    ALKALINE PHOSPHATASE INCREASED 8/46 (17.4%) 12
    ASPARTATE AMINOTRANSFERASE INCREASED 10/46 (21.7%) 11
    BLOOD BILIRUBIN INCREASED 3/46 (6.5%) 5
    CHOLESTEROL HIGH 5/46 (10.9%) 5
    CREATININE INCREASED 5/46 (10.9%) 6
    ELECTROCARDIOGRAM QT CORRECTED INTERVAL PROLONGED 1/46 (2.2%) 1
    INR INCREASED 3/46 (6.5%) 3
    INVESTIGATIONS 8/46 (17.4%) 9
    LYMPHOCYTE COUNT DECREASED 24/46 (52.2%) 79
    NEUTROPHIL COUNT DECREASED 17/46 (37%) 33
    PLATELET COUNT DECREASED 21/46 (45.7%) 58
    WEIGHT GAIN 1/46 (2.2%) 1
    WEIGHT LOSS 14/46 (30.4%) 23
    WHITE BLOOD CELL DECREASED 22/46 (47.8%) 63
    Metabolism and nutrition disorders
    ANOREXIA 12/46 (26.1%) 19
    DEHYDRATION 4/46 (8.7%) 6
    HYPERCALCEMIA 1/46 (2.2%) 1
    HYPERGLYCEMIA 19/46 (41.3%) 46
    HYPERTRIGLYCERIDEMIA 1/46 (2.2%) 1
    HYPERURICEMIA 1/46 (2.2%) 1
    HYPOALBUMINEMIA 10/46 (21.7%) 15
    HYPOCALCEMIA 4/46 (8.7%) 6
    HYPOKALEMIA 14/46 (30.4%) 29
    HYPOMAGNESEMIA 19/46 (41.3%) 33
    HYPONATREMIA 5/46 (10.9%) 10
    HYPOPHOSPHATEMIA 11/46 (23.9%) 17
    METABOLISM AND NUTRITION DISORDERS 3/46 (6.5%) 3
    OBESITY 3/46 (6.5%) 4
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 11/46 (23.9%) 14
    ARTHRITIS 5/46 (10.9%) 5
    BACK PAIN 11/46 (23.9%) 11
    BONE PAIN 1/46 (2.2%) 1
    CHEST WALL PAIN 1/46 (2.2%) 1
    FLANK PAIN 2/46 (4.3%) 2
    GENERALIZED MUSCLE WEAKNESS 1/46 (2.2%) 1
    MUSCLE WEAKNESS LOWER LIMB 2/46 (4.3%) 3
    MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER 6/46 (13%) 9
    MYALGIA 9/46 (19.6%) 11
    MYOSITIS 1/46 (2.2%) 1
    NECK PAIN 3/46 (6.5%) 3
    OSTEOPOROSIS 2/46 (4.3%) 2
    PAIN IN EXTREMITY 8/46 (17.4%) 9
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) 2/46 (4.3%) 2
    Nervous system disorders
    DIZZINESS 8/46 (17.4%) 12
    DYSGEUSIA 6/46 (13%) 8
    HEADACHE 6/46 (13%) 6
    LETHARGY 1/46 (2.2%) 1
    MEMORY IMPAIRMENT 4/46 (8.7%) 5
    NERVOUS SYSTEM DISORDERS 2/46 (4.3%) 2
    PARESTHESIA 1/46 (2.2%) 1
    PERIPHERAL MOTOR NEUROPATHY 1/46 (2.2%) 1
    PERIPHERAL SENSORY NEUROPATHY 26/46 (56.5%) 44
    PRESYNCOPE 1/46 (2.2%) 1
    SYNCOPE 2/46 (4.3%) 2
    Psychiatric disorders
    AGITATION 3/46 (6.5%) 4
    ANXIETY 10/46 (21.7%) 11
    CONFUSION 1/46 (2.2%) 1
    DEPRESSION 7/46 (15.2%) 8
    HALLUCINATIONS 1/46 (2.2%) 1
    INSOMNIA 8/46 (17.4%) 9
    Renal and urinary disorders
    ACUTE KIDNEY INJURY 2/46 (4.3%) 2
    BLADDER SPASM 1/46 (2.2%) 1
    CHRONIC KIDNEY DISEASE 1/46 (2.2%) 1
    CYSTITIS NONINFECTIVE 1/46 (2.2%) 1
    HEMATURIA 11/46 (23.9%) 15
    PROTEINURIA 7/46 (15.2%) 10
    RENAL AND URINARY DISORDERS 7/46 (15.2%) 12
    URINARY FREQUENCY 3/46 (6.5%) 4
    URINARY INCONTINENCE 3/46 (6.5%) 3
    URINARY RETENTION 1/46 (2.2%) 1
    URINARY TRACT OBSTRUCTION 1/46 (2.2%) 1
    URINARY TRACT PAIN 6/46 (13%) 6
    URINARY URGENCY 1/46 (2.2%) 3
    Reproductive system and breast disorders
    PELVIC PAIN 4/46 (8.7%) 5
    REPRODUCTIVE SYSTEM AND BREAST DISORDERS 2/46 (4.3%) 2
    UTERINE HEMORRHAGE 1/46 (2.2%) 1
    VAGINAL DISCHARGE 1/46 (2.2%) 2
    VAGINAL DRYNESS 1/46 (2.2%) 1
    VAGINAL HEMORRHAGE 2/46 (4.3%) 5
    Respiratory, thoracic and mediastinal disorders
    ALLERGIC RHINITIS 3/46 (6.5%) 3
    COUGH 19/46 (41.3%) 21
    DYSPNEA 17/46 (37%) 25
    EPISTAXIS 1/46 (2.2%) 1
    HYPOXIA 1/46 (2.2%) 1
    NASAL CONGESTION 3/46 (6.5%) 3
    PLEURAL EFFUSION 1/46 (2.2%) 1
    PRODUCTIVE COUGH 5/46 (10.9%) 7
    PULMONARY HYPERTENSION 1/46 (2.2%) 1
    RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 4/46 (8.7%) 5
    SORE THROAT 1/46 (2.2%) 1
    WHEEZING 1/46 (2.2%) 1
    Skin and subcutaneous tissue disorders
    ALOPECIA 21/46 (45.7%) 26
    DRY SKIN 4/46 (8.7%) 4
    PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME 2/46 (4.3%) 2
    PRURITUS 6/46 (13%) 7
    RASH ACNEIFORM 4/46 (8.7%) 6
    RASH MACULO-PAPULAR 11/46 (23.9%) 15
    SKIN AND SUBCUTANEOUS TISSUE DISORDERS 5/46 (10.9%) 7
    Vascular disorders
    FLUSHING 1/46 (2.2%) 1
    HYPERTENSION 23/46 (50%) 44
    HYPOTENSION 6/46 (13%) 8
    LYMPHEDEMA 1/46 (2.2%) 1
    THROMBOEMBOLIC EVENT 5/46 (10.9%) 5

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Fauzia Sharmin
    Organization Hoosier Cancer Research Network
    Phone (317) 634-5842 ext 75
    Email fsharmin@hoosiercancer.org
    Responsible Party:
    Daniela Matei, MD, Sponsor-Investigator, Big Ten Cancer Research Consortium
    ClinicalTrials.gov Identifier:
    NCT02549209
    Other Study ID Numbers:
    • BTCRC GYN15-013
    First Posted:
    Sep 15, 2015
    Last Update Posted:
    Mar 2, 2022
    Last Verified:
    Feb 1, 2022