Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer

Sponsor
UNC Lineberger Comprehensive Cancer Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02768701
Collaborator
Merck Sharp & Dohme LLC (Industry)
40
5
1
76.4
8
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate pembrolizumab therapy in patients with triple-negative breast cancer (TNBC) who have received at least one prior line of therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This phase II, single-arm, multicenter study will evaluate efficacy and toxicity of administration of pembrolizumab following cyclophosphamide therapy, in advanced stage triple-negative breast cancer.

Duration of Therapy

Treatment may continue until one of the following occurs:
  • Disease progression

  • Inter-current illness that prevents further administration of treatment

  • Unacceptable adverse event(s)

  • Pregnancy

  • Patient decides to withdraw from study treatment,

  • General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator

  • Completed 24 months of uninterrupted treatment with pembrolizumab or 35 administrations of study medication, whichever is later

Duration of Follow Up

  • Subjects will be followed for up to 3 years after removal from study treatment or until death, whichever occurs first.

  • Patients removed from study for unacceptable adverse events (AEs) will be followed until resolution or stabilization of the event(s).

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study Of Single-dose Cyclophosphamide +Pembrolizumab In Patients With Metastatic Triple Negative Breast Cancer
Actual Study Start Date :
Oct 18, 2016
Actual Primary Completion Date :
Mar 1, 2022
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental: Single Arm

Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks.

Drug: Pembrolizumab
Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion.
Other Names:
  • Keytruda
  • Drug: Cyclophosphamide
    A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Other Names:
  • Cytoxan
  • Neosar
  • Outcome Measures

    Primary Outcome Measures

    1. The Progression Free Survival (PFS) [Up to 5 years]

      PFS is defined as the time from day1 of the study treatment until disease progression or death. Disease progression is defined as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images or assessment of the physician. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    2. Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment. [Up to 2 years]

      Regulatory T cells (Tregs) are counted before the treatment start and during the treatment. Methods: Blood Sample collection.

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 2 years]

      ORR is defined as the percentage of patients with [compete response (CR) + partial response (PR)] per RECIST1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;

    2. Duration of Response (DOR) [Up to 3 years]

      DOR is defined as the time from documentation of tumor response by RECIST1.1 [(CR) + (PR)] to disease progression by RECIST 1.1. It will be measured from when the time measurement criteria are first met for complete response or partial response (whichever status is recorded first) until the first date of progressive disease or death. Patients who neither progress nor die will be censored on the date of their last tumor assessment.

    3. Disease Control Rate (DCR) [Up to 2 years]

      DCR is defined as the percentage of participants, who achieve [compete response (CR) + partial response (PR) and stable disease (SD) per RECIST1.1. If best response is SD, then it must last more than 6 months to be included in calculation of DCR, to be considered to have received clinical benefit from the treatment regimen. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    4. Overall Survival (OS) [Up to 3 years]

      OS is defined as the time from D1 of study treatment to death from any cause.

    5. Treatment Associated Toxicity [Up to 3 years]

      Treatment Associated Toxicity is defined as the number of participants with Grade 3-4 adverse events associated with study treatment. Adverse Events were classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

    2. Age ≥ 18 years at the time of consent.

    3. Have measurable disease based on RECIST 1.1 (see section 6.7 for details).

    4. ECOG Performance Status ≤ 1 as defined in the protocol ECOG Performance Status.

    5. Subject must have histologically confirmed stage IV TNBC (ER-, PR-, HER2-negative) and have received at least 1 prior line of systemic therapy.

    • ER- and PR-negative: defined as < 1% staining by immunohistochemistry (IHC)

    • HER2-negative disease, defined as IHC 0-1+ or fluorescence in situ hybridization (FISH) ratio < 2.0

    1. Patients with stable brain metastases will be allowed provided the following criteria are met:
    • Brain radiation was already provided at least 4 weeks prior to initiating study treatment

    • The subject has no new or progressive neurologic symptoms AND neurological symptom stability for the last 4 weeks prior to the study

    • The subject has been off of corticosteroids for at least 7 days prior to trial treatment

    • The subject does not have carcinomatous meningitis

    1. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 h of initiating study treatment.

    2. Females of childbearing potential must have a negative serum pregnancy test within 72 hrs prior to treatment. NOTE: Females are considered of child bearing potential unless they are surgically sterile, have a congenital acquired condition that prevents childbearing (have undergone a hysterectomy, bilateral tubal ligation/occlusion, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to screening) or they are naturally postmenopausal for at least 12 consecutive months without an alternative medical cause. In women < 45 years of age a high follicle stimulating hormone level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

    3. Female patients of childbearing potential should be willing to use appropriate birth control as outlined in Section 5.2.8, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.

    4. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 5.2.8, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    5. Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment; fresh biopsy (pre and post dose) of tumor tissue will be optional. NOTE: Patients without adequate tissue for bio correlates will not be excluded or required to have a repeat biopsy.

    6. As determined by the enrolling physician or protocol designee, the subject should be able to understand and comply with study procedures for the entire length of the study.

    7. Has a LVEF within the normal institutional range (or ≥ 50%) based on ECHO or MUGA.

    Exclusion Criteria:
    1. Active infection requiring systemic therapy

    2. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

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

    4. Hypersensitivity to pembrolizumab or any of its excipients.

    5. Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.

    6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to receipt of study medication or who has not recovered (i.e., ≤ Grade 1 or at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to a previously administered agent.

    • If subject had major surgery, they must have recovered adequately from the toxicity and complications from the intervention prior to starting therapy

    1. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

    2. Has had monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (ie, ≤ Grade 1 at baseline; excludes alopecia and Grade 2 neuropathy) from adverse events due to agent(s) administered more than 4 weeks earlier.

    3. Treatment with any investigational drug within 4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study medication.

    4. Used an investigational device within 4 weeks of the first dose of treatment.

    5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

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

    7. Has known history of, or any evidence of active, non-infectious pneumonitis requiring treatment with steroids; has history of, or any evidence of, active interstitial lung disease.

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

    9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

    10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

    11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

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

    13. Has participated in a previous trial and received pembrolizumab therapy

    14. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

    15. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

    • 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

    1. Cyclophosphamide is a substrate for cytochromes 2B6, 2C9, 3A4 and 2C19. Patients must not have received any drug that is a moderate or strong inhibitor of 2B6, 2C9, 3A4, and 2C19 within 1 week prior to receiving cyclophosphamide dosing through 72 hours after cyclophosphamide dosing. Patients must not have received any drug that is a moderate or strong inducer of 3A4 within 2 weeks prior to cyclophosphamide dosing.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 George Washington University-Medical Faculty Associates Washington District of Columbia United States 20037
    2 Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    3 Cone Health Cancer Center Greensboro North Carolina United States 27403
    4 Rex Cancer Center Raleigh North Carolina United States 27607
    5 University of Pittsburgh Medical Center Pittsburgh Pennsylvania United States 15213

    Sponsors and Collaborators

    • UNC Lineberger Comprehensive Cancer Center
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Elizabeth C Dees, MD, UNC Lineberger Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    UNC Lineberger Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02768701
    Other Study ID Numbers:
    • LCCC 1525
    First Posted:
    May 11, 2016
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by UNC Lineberger Comprehensive Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Subjects were enrolled at five institutions (UNC-Chapel Hill, University of Pittsburgh, Moses Cone, UNC-Rex Cancer Center, and George Washington University) from November, 2016 to February, 2018. All subjects started to receive study treatment in November 2016 although 2 subjects signed informed consent in October 2016.
    Pre-assignment Detail A total of forty-nine subjects consented to the study, but eight were deemed to be ineligible and one subject has withdrawn the consent during screening. Forty subjects were enrolled and evaluable for toxicity and survival, and 39 subjects were evaluable for response.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Period Title: Overall Study
    STARTED 40
    COMPLETED 32
    NOT COMPLETED 8

    Baseline Characteristics

    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Overall Participants 40
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    32
    80%
    >=65 years
    8
    20%
    Sex: Female, Male (Count of Participants)
    Female
    40
    100%
    Male
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    8
    20%
    White
    28
    70%
    More than one race
    1
    2.5%
    Unknown or Not Reported
    3
    7.5%
    Region of Enrollment (participants) [Number]
    United States
    40
    100%
    ECOG performance status (Count of Participants)
    0
    24
    60%
    1
    16
    40%
    Stage at diagnosis (Count of Participants)
    0-III
    30
    75%
    IV
    10
    25%
    Prior (neo)adjuvant therapy (Count of Participants)
    Yes
    33
    82.5%
    No
    7
    17.5%
    Sites of metastatic disease (Count of Participants)
    Liver
    12
    30%
    Lung
    14
    35%
    Bone
    18
    45%
    Lymph node
    4
    10%
    Brain
    1
    2.5%

    Outcome Measures

    1. Primary Outcome
    Title The Progression Free Survival (PFS)
    Description PFS is defined as the time from day1 of the study treatment until disease progression or death. Disease progression is defined as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST)1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images or assessment of the physician. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    The subjects received at least one dose of the study treatment were included.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 35
    Median (95% Confidence Interval) [months]
    1.8
    2. Primary Outcome
    Title Quantification of the Change in Regulatory T Cells (Tregs) During the Study Treatment.
    Description Regulatory T cells (Tregs) are counted before the treatment start and during the treatment. Methods: Blood Sample collection.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    The subjects received two doses of the study treatment.
    Arm/Group Title C1D1-C1D2 C1D1-C2D1 C1D2-C2D1
    Arm/Group Description Changes in Tregs count value from Cycle 1 Day 1 to Cycle 1 Day 2 Changes in Tregs count value from Cycle 1 Day 1 to Cycle 2 Day 1 Changes in Tregs count value from Cycle 1 Day 2 to Cycle 2 Day 1
    Measure Participants 40 40 40
    Median (Full Range) [Percent Change in Tregs]
    -3.3
    10
    21.7
    3. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description ORR is defined as the percentage of patients with [compete response (CR) + partial response (PR)] per RECIST1.1 based on computerized tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) images. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions;
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    The subjects received at least one dose of the study treatment and treatments response was assessed.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 39
    Number [percentage of participants]
    21
    52.5%
    4. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR is defined as the time from documentation of tumor response by RECIST1.1 [(CR) + (PR)] to disease progression by RECIST 1.1. It will be measured from when the time measurement criteria are first met for complete response or partial response (whichever status is recorded first) until the first date of progressive disease or death. Patients who neither progress nor die will be censored on the date of their last tumor assessment.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    The subjects received at least one dose of the study treatment and treatments response was assessed.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 39
    Median (Full Range) [months]
    20.4
    5. Secondary Outcome
    Title Disease Control Rate (DCR)
    Description DCR is defined as the percentage of participants, who achieve [compete response (CR) + partial response (PR) and stable disease (SD) per RECIST1.1. If best response is SD, then it must last more than 6 months to be included in calculation of DCR, to be considered to have received clinical benefit from the treatment regimen. RECIST v.1.1: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    The subjects received the study treatment, treatments response was assessed and/or followed up for more than 6 months.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 39
    Count of Participants [Participants]
    28
    70%
    6. Secondary Outcome
    Title Overall Survival (OS)
    Description OS is defined as the time from D1 of study treatment to death from any cause.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    All subjects who received at least one dose of treatment were included.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 35
    Median (95% Confidence Interval) [months]
    6.3
    7. Secondary Outcome
    Title Treatment Associated Toxicity
    Description Treatment Associated Toxicity is defined as the number of participants with Grade 3-4 adverse events associated with study treatment. Adverse Events were classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Participants who received at least one cycle of study treatment were included.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    Measure Participants 40
    White blood cell decreased
    2
    5%
    Pericardial tamponade
    1
    2.5%
    Pain
    1
    2.5%
    Neutrophil count decreased
    2
    5%
    Lymphocyte count decreased
    1
    2.5%
    Immune system disorders
    1
    2.5%
    Hypoalbuminemia
    1
    2.5%
    Headache
    1
    2.5%
    Generalized muscle weakness
    1
    2.5%
    Gastrointestinal disorders
    1
    2.5%
    Fatigue
    3
    7.5%
    Dyspnea
    2
    5%
    Dry mouth
    1
    2.5%
    Diarrhea
    2
    5%
    Colitis
    1
    2.5%
    Blood bilirubin increased
    1
    2.5%
    Aspartate aminotransferase increased
    2
    5%
    Anorexia
    1
    2.5%
    Anemia
    2
    5%
    Alkaline phosphatase increased
    1
    2.5%
    Alanine aminotransferase increased
    1
    2.5%

    Adverse Events

    Time Frame From day 1 of the study treatment up to 3 years
    Adverse Event Reporting Description Treatment Associated Toxicity will be graded number of participants with Adverse Events. Adverse Events will be classified and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 based on changes in laboratory parameters, vital signs, and other safety assessments per standard of care.
    Arm/Group Title Experimental: Single Arm
    Arm/Group Description Subjects will receive a single dose (300 mg/m2) of cyclophosphamide given the day before cycle 1 of pembrolizumab (200 mg), which will be administered every 3 weeks. Pembrolizumab: Subjects will be treated every 3 weeks with 200 mg of pembrolizumab via a 30 minute infusion. Cyclophosphamide: A single 300 mg/m2 dose of cyclophosphamide IV over 30-60 minutes will be administered on Day 1 of this study.
    All Cause Mortality
    Experimental: Single Arm
    Affected / at Risk (%) # Events
    Total 5/40 (12.5%)
    Serious Adverse Events
    Experimental: Single Arm
    Affected / at Risk (%) # Events
    Total 18/40 (45%)
    Blood and lymphatic system disorders
    Anemia 1/40 (2.5%)
    Cardiac disorders
    Pericardial tamponade 1/40 (2.5%)
    Myocardial infarction 1/40 (2.5%)
    Supraventricular tachycardia 1/40 (2.5%)
    Gastrointestinal disorders
    Vomiting 1/40 (2.5%)
    Abdominal pain 2/40 (5%)
    Colitis 1/40 (2.5%)
    Gastrointestinal disorders - Other, specify 1/40 (2.5%)
    Colonic perforation 1/40 (2.5%)
    General disorders
    Pain 1/40 (2.5%)
    Fever 1/40 (2.5%)
    Infections and infestations
    Infections and infestations - Other, specify 1/40 (2.5%)
    Sepsis 2/40 (5%)
    Investigations
    Investigations - Other, specify 1/40 (2.5%)
    Alkaline phosphatase increased 1/40 (2.5%)
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness 2/40 (5%)
    Muscle weakness lower limb 1/40 (2.5%)
    Musculoskeletal and connective tissue disorder - Other, specify 1/40 (2.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 3/40 (7.5%)
    Nervous system disorders
    Lethargy 1/40 (2.5%)
    Presyncope 1/40 (2.5%)
    Seizure 1/40 (2.5%)
    Nervous system disorders - Other, specify 1/40 (2.5%)
    Paresthesia 1/40 (2.5%)
    Renal and urinary disorders
    Renal and urinary disorders - Other, specify 1/40 (2.5%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 3/40 (7.5%)
    Respiratory, thoracic and mediastinal disorders - Other, specify 1/40 (2.5%)
    Pleural effusion 1/40 (2.5%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 1/40 (2.5%)
    Other (Not Including Serious) Adverse Events
    Experimental: Single Arm
    Affected / at Risk (%) # Events
    Total 40/40 (100%)
    Blood and lymphatic system disorders
    Anemia 28/40 (70%)
    Blood and lymphatic system disorders - Other, specify 1/40 (2.5%)
    Leukocytosis 1/40 (2.5%)
    Lymph node pain 5/40 (12.5%)
    Cardiac disorders
    Cardiac disorders - Other, specify 3/40 (7.5%)
    Palpitations 2/40 (5%)
    Pericardial effusion 1/40 (2.5%)
    Pericardial tamponade 1/40 (2.5%)
    Sinus tachycardia 6/40 (15%)
    Supraventricular tachycardia 1/40 (2.5%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other, specify 1/40 (2.5%)
    Hearing impaired 1/40 (2.5%)
    Tinnitus 1/40 (2.5%)
    Vertigo 3/40 (7.5%)
    Endocrine disorders
    Endocrine disorders - Other, specify 2/40 (5%)
    Hyperthyroidism 5/40 (12.5%)
    Hypothyroidism 9/40 (22.5%)
    Eye disorders
    Blurred vision 1/40 (2.5%)
    Dry eye 4/40 (10%)
    Eye disorders - Other, specify 3/40 (7.5%)
    Scleral disorder 1/40 (2.5%)
    Gastrointestinal disorders
    Abdominal distension 1/40 (2.5%)
    Abdominal pain 8/40 (20%)
    Ascites 1/40 (2.5%)
    Bloating 1/40 (2.5%)
    Colitis 3/40 (7.5%)
    Constipation 21/40 (52.5%)
    Diarrhea 12/40 (30%)
    Dry mouth 5/40 (12.5%)
    Dyspepsia 1/40 (2.5%)
    Dysphagia 2/40 (5%)
    Gastroesophageal reflux disease 9/40 (22.5%)
    Gastrointestinal disorders - Other, specify 2/40 (5%)
    Mucositis oral 3/40 (7.5%)
    Nausea 20/40 (50%)
    Oral dysesthesia 1/40 (2.5%)
    Vomiting 7/40 (17.5%)
    General disorders
    Chills 3/40 (7.5%)
    Edema face 2/40 (5%)
    Edema limbs 13/40 (32.5%)
    Fatigue 30/40 (75%)
    Fever 2/40 (5%)
    Flu like symptoms 1/40 (2.5%)
    General disorders and administration site conditions - Other, specify 7/40 (17.5%)
    Irritability 2/40 (5%)
    Non-cardiac chest pain 2/40 (5%)
    Pain 11/40 (27.5%)
    Immune system disorders
    Immune system disorders - Other, specify 1/40 (2.5%)
    Infections and infestations
    Infections and infestations - Other, specify 4/40 (10%)
    Lung infection 1/40 (2.5%)
    Mucosal infection 2/40 (5%)
    Rash pustular 1/40 (2.5%)
    Sinusitis 1/40 (2.5%)
    Upper respiratory infection 1/40 (2.5%)
    Urinary tract infection 5/40 (12.5%)
    Injury, poisoning and procedural complications
    Bruising 1/40 (2.5%)
    Fracture 2/40 (5%)
    Injury, poisoning and procedural complications - Other, specify 2/40 (5%)
    Spinal fracture 2/40 (5%)
    Activated partial thromboplastin time prolonged 2/40 (5%)
    Investigations
    Alanine aminotransferase increased 12/40 (30%)
    Alkaline phosphatase increased 8/40 (20%)
    Aspartate aminotransferase increased 17/40 (42.5%)
    Blood bilirubin increased 3/40 (7.5%)
    Cholesterol high 3/40 (7.5%)
    Creatinine increased 4/40 (10%)
    Investigations - Other, specify 2/40 (5%)
    Lymphocyte count decreased 25/40 (62.5%)
    Neutrophil count decreased 7/40 (17.5%)
    Platelet count decreased 2/40 (5%)
    Weight gain 1/40 (2.5%)
    Weight loss 3/40 (7.5%)
    White blood cell decreased 11/40 (27.5%)
    Metabolism and nutrition disorders
    Acidosis 1/40 (2.5%)
    Anorexia 13/40 (32.5%)
    Dehydration 1/40 (2.5%)
    Glucose intolerance 1/40 (2.5%)
    Hypercalcemia 1/40 (2.5%)
    Hyperglycemia 5/40 (12.5%)
    Hyperkalemia 2/40 (5%)
    Hypernatremia 1/40 (2.5%)
    Hypoalbuminemia 15/40 (37.5%)
    Hypocalcemia 7/40 (17.5%)
    Hypoglycemia 1/40 (2.5%)
    Hypokalemia 9/40 (22.5%)
    Hypomagnesemia 10/40 (25%)
    Hyponatremia 15/40 (37.5%)
    Hypophosphatemia 1/40 (2.5%)
    Metabolism and nutrition disorders - Other, specify 4/40 (10%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/40 (15%)
    Arthritis 4/40 (10%)
    Back pain 8/40 (20%)
    Bone pain 4/40 (10%)
    Chest wall pain 4/40 (10%)
    Flank pain 1/40 (2.5%)
    Generalized muscle weakness 3/40 (7.5%)
    Muscle weakness lower limb 3/40 (7.5%)
    Muscle weakness upper limb 2/40 (5%)
    Musculoskeletal and connective tissue disorder - Other, specify 5/40 (12.5%)
    Myalgia 5/40 (12.5%)
    Myositis 1/40 (2.5%)
    Neck pain 4/40 (10%)
    Osteoporosis 1/40 (2.5%)
    Pain in extremity 8/40 (20%)
    Nervous system disorders
    Akathisia 1/40 (2.5%)
    Amnesia 1/40 (2.5%)
    Brachial plexopathy 1/40 (2.5%)
    Dizziness 4/40 (10%)
    Dysarthria 1/40 (2.5%)
    Dysgeusia 2/40 (5%)
    Headache 9/40 (22.5%)
    Memory impairment 1/40 (2.5%)
    Nervous system disorders - Other, specify 1/40 (2.5%)
    Neuralgia 1/40 (2.5%)
    Paresthesia 2/40 (5%)
    Peripheral motor neuropathy 2/40 (5%)
    Peripheral sensory neuropathy 17/40 (42.5%)
    Presyncope 1/40 (2.5%)
    Seizure 1/40 (2.5%)
    Sinus pain 2/40 (5%)
    Somnolence 1/40 (2.5%)
    Tremor 1/40 (2.5%)
    Psychiatric disorders
    Agitation 2/40 (5%)
    Anxiety 17/40 (42.5%)
    Confusion 2/40 (5%)
    Depression 9/40 (22.5%)
    Insomnia 17/40 (42.5%)
    Libido decreased 2/40 (5%)
    Restlessness 1/40 (2.5%)
    Renal and urinary disorders
    Renal and urinary disorders - Other, specify 3/40 (7.5%)
    Urinary frequency 3/40 (7.5%)
    Urinary incontinence 3/40 (7.5%)
    Urinary urgency 3/40 (7.5%)
    Urine discoloration 1/40 (2.5%)
    Reproductive system and breast disorders
    Breast pain 2/40 (5%)
    Pelvic pain 1/40 (2.5%)
    Reproductive system and breast disorders - Other, specify 1/40 (2.5%)
    Vaginal dryness 3/40 (7.5%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 6/40 (15%)
    Cough 15/40 (37.5%)
    Dyspnea 17/40 (42.5%)
    Epistaxis 1/40 (2.5%)
    Hoarseness 2/40 (5%)
    Hypoxia 1/40 (2.5%)
    Nasal congestion 2/40 (5%)
    Pleural effusion 8/40 (20%)
    Pneumonitis 2/40 (5%)
    Respiratory, thoracic and mediastinal disorders - Other, specify 3/40 (7.5%)
    Sinus disorder 1/40 (2.5%)
    Sleep apnea 1/40 (2.5%)
    Sore throat 3/40 (7.5%)
    Voice alteration 1/40 (2.5%)
    Wheezing 1/40 (2.5%)
    Skin and subcutaneous tissue disorders
    Alopecia 6/40 (15%)
    Body odor 1/40 (2.5%)
    Dry skin 4/40 (10%)
    Pain of skin 2/40 (5%)
    Palmar-plantar erythrodysesthesia syndrome 1/40 (2.5%)
    Pruritus 4/40 (10%)
    Rash acneiform 1/40 (2.5%)
    Rash maculo-papular 7/40 (17.5%)
    Skin and subcutaneous tissue disorders - Other, specify 10/40 (25%)
    Skin hyperpigmentation 1/40 (2.5%)
    Surgical and medical procedures - Other, specify 1/40 (2.5%)
    Vascular disorders
    Flushing 1/40 (2.5%)
    Hematoma 1/40 (2.5%)
    Hot flashes 5/40 (12.5%)
    Hypertension 16/40 (40%)
    Lymphedema 11/40 (27.5%)
    Thromboembolic event 2/40 (5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Melahat G. Canter MD MS ACRP-CP, Clinical Trial Analyst
    Organization University of North Carolina Lineberger Comprehensive Cancer Center
    Phone (919) 962-0000
    Email Melahat_Canter@med.unc.edu
    Responsible Party:
    UNC Lineberger Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02768701
    Other Study ID Numbers:
    • LCCC 1525
    First Posted:
    May 11, 2016
    Last Update Posted:
    Aug 3, 2022
    Last Verified:
    Jul 1, 2022