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Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03914612
Recruitment Status : Recruiting
First Posted : April 16, 2019
Last Update Posted : April 2, 2020
Sponsor:
Collaborator:
NRG Oncology
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE April 12, 2019
First Posted Date  ICMJE April 16, 2019
Last Update Posted Date April 2, 2020
Actual Study Start Date  ICMJE July 16, 2019
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
Progression-free survival (PFS) [ Time Frame: Duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years ]
Will be tested with a stratified log-rank statistic.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2019)
  • Incidence of adverse events [ Time Frame: 5 years ]
    Assessed by Common Terminology Criteria for Adverse Events (CTCAE). Toxicities will be screened for differences between treatments by using an exact method or a Chi-Square test. For a given adverse event, each patient will be graded according to the worse grade experienced while on therapy (and within 30 days of treatment). These toxicities will then be divided into two or three categories such as mild, moderate, and severe or mild to moderate versus severe. The rates of severe toxicities may be characterized by risk ratios or odds ratios with confidence intervals (unadjusted for multiplicity). The number of toxicities examined is usually fairly large, so these analyses will be considered exploratory and may be inspected in light of other studies.
  • Objective tumor response [ Time Frame: 5 years ]
    Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.
  • Duration of objective response [ Time Frame: 5 years ]
    The time difference between the dates of first response and first progression; patients who do not progress are considered censored.
  • Overall survival (OS) [ Time Frame: Time from study entry to time of death or the date of last contact, assessed up to 5 years ]
  • Quality of life (QoL) and patient-reported outcomes (PROs) [ Time Frame: 5 years ]
    Measured by the Function Assessment of Cancer Therapy (FACT)-Endometrial Trial Outcome Index (En-TOI), the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (short), Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue (short form),the PROMIS-physical function (short form) and a single-item measuring bother from side effects of cancer therapy. A linear mixed model for repeated measures will be used to estimate and compare the mean differences between the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, pre-treatment quality of life/patient reported outcome score, assessment time and treatment-by-time interaction. The stratification factors will be the same factors included in the clinical primary analysis. Hochberg's step-up multiple testing procedure (Hochberg, 1988) will be used to adjust p-values for each assessment time points estimated from the fitted model.
  • Incidence of pembrolizumab treatment and self-reported neurotoxicity [ Time Frame: 5 years ]
    Assessed with FACT/GOG-Ntx.
  • Concordance between Institutional Mismatch repair (MMR) immunohistochemistry (IHC) testing and centralized MMR IHC [ Time Frame: 5 years ]
    Concordance between institutional MMR IHC testing and centralized MMR IHC. The patient's MMR status will be assessed for prognostic value by conducting stratified log-rank tests or Cox Proportional Hazards (PH) modeling when assessing the impact on PFS or OS. When assessing the impact on the probability of response, a logistic regression model will be considered and include other pertinent variables that may influence response. A Cox PH model will be used to assess predictive value of MMR status for regimen efficacy through an interaction term. A similar type of analysis may be attempted with response using logistic regression. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
  • Effect of pembrolizumab on PFS and OS by PD-L1 IHC [ Time Frame: 5 years ]
    Will assess the effect of pembrolizumab on PFS and OS by PD-L1 IHC (combined positive score [CPS]) within proficient MMR (pMMR) and deficient MMR (dMMR) populations. The effectiveness of pembrolizumab will be compared by PD-L1 status (CPS). A formal test will be conducted by examining the interaction term between pembrolizumab treatment (yes or no) with PD-L1 status. The association between PD-L1 CPS status and MMR status will be assessed with odds ratios. A test may be conducted with a Fisher's Exact Test, and confidence intervals will be provided.
  • Association between Program Death Ligand 1 (PD-L1) IHC and MMR status [ Time Frame: 5 years ]
    Measures of association between PD-L1 IHC (CPS) and MMR status. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Incidence of adverse events [ Time Frame: 5 years ]
    Assessed by Common Terminology Criteria for Adverse Events (CTCAE). Toxicities will be screened for differences between treatments by using an exact method or a Chi-Square test. For a given adverse event, each patient will be graded according to the worse grade experienced while on therapy (and within 30 days of treatment). These toxicities will then be divided into two or three categories such as mild, moderate, and severe or mild to moderate versus severe. The rates of severe toxicities may be characterized by risk ratios or odds ratios with confidence intervals (unadjusted for multiplicity). The number of toxicities examined is usually fairly large, so these analyses will be considered exploratory and may be inspected in light of other studies.
  • Objective tumor response [ Time Frame: 5 years ]
    Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.
  • Duration of objective response [ Time Frame: 5 years ]
    The time difference between the dates of first response and first progression; patients who do not progress are considered censored.
  • Overall survival (OS) [ Time Frame: Time from study entry to time of death or the date of last contact, assessed up to 5 years ]
  • Quality of life (QoL) and patient-reported outcomes (PROs) [ Time Frame: 5 years ]
    Measured by the Function Assessment of Cancer Therapy (FACT)-Endometrial Trial Outcome Index (En-TOI), the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (short), Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue (short form),the PROMIS-physical function (short form) and a single-item measuring bother from side effects of cancer therapy. A linear mixed model for repeated measures will be used to estimate and compare the mean differences between the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, pre-treatment quality of life/patient reported outcome score, assessment time and treatment-by-time interaction. The stratification factors will be the same factors included in the clinical primary analysis. Hochberg's step-up multiple testing procedure (Hochberg, 1988) will be used to adjust p-values for each assessment time points estimated from the fitted model.
  • Incidence of pembrolizumab treatment and self-reported neurotoxicity [ Time Frame: 5 years ]
    Assessed with FACT/GOG-Ntx.
  • Mismatch repair (MMR) immunohistochemistry (IHC) [ Time Frame: 5 years ]
    Concordance between institutional MMR IHC testing and centralized MMR IHC. The patient's MMR status will be assessed for prognostic value by conducting stratified log-rank tests or Cox Proportional Hazards (PH) modeling when assessing the impact on PFS or OS. When assessing the impact on the probability of response, a logistic regression model will be considered and include other pertinent variables that may influence response. A Cox PH model will be used to assess predictive value of MMR status for regimen efficacy through an interaction term. A similar type of analysis may be attempted with response using logistic regression. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
  • PD-L1 IHC [ Time Frame: 5 years ]
    Will assess the effect of pembrolizumab on PFS and OS by PD-L1 IHC (combined positive score [CPS]) within proficient MMR (pMMR) and deficient MMR (dMMR) populations. The effectiveness of pembrolizumab will be compared by PD-L1 status (CPS). A formal test will be conducted by examining the interaction term between pembrolizumab treatment (yes or no) with PD-L1 status. The association between PD-L1 CPS status and MMR status will be assessed with odds ratios. A test may be conducted with a Fisher's Exact Test, and confidence intervals will be provided.
  • PD-L1 IHC status [ Time Frame: 5 years ]
    Measures of association between PD-L1 IHC (CPS) and MMR status. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer
Official Title  ICMJE A Phase III Randomized, Placebo-Controlled Study of Pembrolizumab (MK-3475, NSC #776864) in Addition to Paclitaxel and Carboplatin for Measurable Stage III or IVA, Stage IVB or Recurrent Endometrial Cancer
Brief Summary This phase III trial studies how well the combination of pembrolizumab, paclitaxel and carboplatin works compared with paclitaxel and carboplatin alone in treating patients with endometrial cancer that is stage III or IV, or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel and carboplatin are chemotherapy drugs used as part of the usual treatment approach for this type of cancer. This study aims to assess if adding immunotherapy to these drugs is better or worse than the usual approach for treatment of this cancer.
Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of pembrolizumab in combination with paclitaxel and carboplatin in patients with advanced stage (measurable stage III or IVA), stage IVB and recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) for each treatment arm.

II. To evaluate blinded independent central review (BICR) assessed or investigator assessed objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by treatment arm and by mismatch repair (MMR) status in patients who enter the study with measurable disease.

III. To evaluate BICR assessed or investigator assessed duration of response (DOR) by treatment arm and by MMR status in patients who enter the study with measurable disease.

IV. To evaluate the effect of pembrolizumab on overall survival (OS) in patients with mismatch repair protein proficient (pMMR) or mismatch repair deficiency (dMMR).

V. To determine whether the addition of pembrolizumab to standard combination chemotherapy is associated with improved patient reported physical function as measured with the Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function scale (short form), quality of life as measured with the Functional Assessment of Cancer Therapy (FACT) - Endometrial Trial Outcome Index (En TOI) and worsened fatigue as measured with the PROMIS-Fatigue scale (short form) in the pMMR patients.

VI. To determine concordance between institutional MMR immunohistochemistry (IHC) testing and centralized MMR IHC.

EXPLORATORY OBJECTIVES:

I. To explore the correlation between patient-reported physical function as measured with the PROMIS-physical function scale (short form) and quality of life as measure with the FACT-En TOI.

II. To explore whether the addition of pembrolizumab to standard combination chemotherapy is associated with self-reported neurotoxicity as measured with the FACT/Gynecologic Oncology Group Neurotoxicity (GOG-Ntx) subscale (short) and the extent to which patients differ on their self-reported bother from side effects of cancer therapy in the pMMR patients.

III. To evaluate the efficacy of pembrolizumab in combination with paclitaxel and carboplatin in patients with advanced stage (measurable stage III or IVA), stage IVB and recurrent endometrial cancer by PD-L1 IHC (positive versus [vs] negative).

IV. To assess the association between PD-L1 IHC (positive vs negative) and mismatch repair status (pMMR and dMMR).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

COMBINATION PHASE: Patients receive placebo intravenously (IV) over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) who still have measurable disease may continue treatment for up to a total 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.

ARM II:

COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Endometrial Clear Cell Adenocarcinoma
  • Endometrial Dedifferentiated Carcinoma
  • Endometrial Endometrioid Adenocarcinoma
  • Endometrial Mixed Cell Adenocarcinoma
  • Endometrial Serous Adenocarcinoma
  • Endometrial Undifferentiated Carcinoma
  • Recurrent Endometrial Adenocarcinoma
  • Recurrent Endometrial Carcinoma
  • Recurrent Endometrial Clear Cell Adenocarcinoma
  • Recurrent Endometrial Dedifferentiated Carcinoma
  • Recurrent Endometrial Endometrioid Adenocarcinoma
  • Recurrent Endometrial Mixed Cell Adenocarcinoma
  • Recurrent Endometrial Serous Adenocarcinoma
  • Recurrent Endometrial Undifferentiated Carcinoma
  • Stage III Uterine Corpus Cancer AJCC v8
  • Stage IIIA Uterine Corpus Cancer AJCC v8
  • Stage IIIB Uterine Corpus Cancer AJCC v8
  • Stage IIIC Uterine Corpus Cancer AJCC v8
  • Stage IIIC1 Uterine Corpus Cancer AJCC v8
  • Stage IIIC2 Uterine Corpus Cancer AJCC v8
  • Stage IV Uterine Corpus Cancer AJCC v8
  • Stage IVA Uterine Corpus Cancer AJCC v8
  • Stage IVB Uterine Corpus Cancer AJCC v8
Intervention  ICMJE
  • Drug: Carboplatin
    Given IV
    Other Names:
    • Blastocarb
    • Carboplat
    • Carboplatin Hexal
    • Carboplatino
    • Carboplatinum
    • Carbosin
    • Carbosol
    • Carbotec
    • CBDCA
    • Displata
    • Ercar
    • JM-8
    • Nealorin
    • Novoplatinum
    • Paraplatin
    • Paraplatin AQ
    • Paraplatine
    • Platinwas
    • Ribocarbo
  • Drug: Paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Biological: Pembrolizumab
    Given IV
    Other Names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Other: Placebo Administration
    Given IV
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • Active Comparator: Arm I (placebo, paclitaxel, carboplatin)

    COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

    MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Other: Placebo Administration
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • Experimental: Arm II (pembrolizumab, paclitaxel, carboplatin)

    COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

    MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 29 cycles in the absence of disease progression or unacceptable toxicity.

    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Biological: Pembrolizumab
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 12, 2019)
810
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
  • Pathology report showing results of institutional MMR IHC testing.
  • Histologic confirmation of the original primary tumor is required (submission of pathology report(s) is required). Patients with the following histologic types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.).
  • Submission of tumor specimens for centralized MMR IHC testing is required after Step 1 and before Step 2 registration.
  • In patients with measurable disease (stage III and IVA), lesions will be defined and monitored by RECIST version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
  • Patients may have received

    • NO prior chemotherapy for treatment of endometrial cancer OR
    • Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy [with or without cisplatin]) provided adjuvant chemotherapy was completed >= 12 months prior to STEP 2 registration.
  • Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to STEP 2 registration.
  • Patients may have received prior hormonal therapy for treatment of endometrial cancer. All hormonal therapy must be discontinued at least three weeks prior to STEP 2 registration.
  • Performance status of 0, 1 or 2.
  • Platelets >= 100,000/mcl.
  • Absolute neutrophil count (ANC) >= 1,500/mcl.
  • Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN).
  • Total serum bilirubin level =< 1.5 x upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN.
  • Thyroid stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy).
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 2 registration are eligible for this trial.
  • For patients of child bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
  • Administration of study drugs (pembrolizumab, paclitaxel, carboplatin) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from at least 14 days prior to Step 2 registration (for oral contraceptives), during treatment, and for 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Patients will be considered of nonreproductive potential if they are either:

    • Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal 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); OR
    • Have a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to Step 2 registration; OR
    • Have a congenital or acquired condition that prevents childbearing.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information.

Exclusion Criteria:

  • Patients with prior treatment with anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.
  • Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or pembrolizumab and/or its excipients.
  • Patients who are currently participating and receiving cancer-directed study therapy or have participated in a study of an investigational agent and received cancer-directed study therapy within 4 weeks prior to Step 2 registration.
  • Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Step 2 registration.

    • Patients who have received steroids as CT scan contrast premedication may be enrolled.
    • The use of inhaled or topical corticosteroids is allowed.
    • The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
    • The use of physiologic doses of corticosteroids may be approved after consultation with the study chair.
  • Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, and they have been off steroids for at least 4 weeks prior to Step 2 registration and remain clinically stable.
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
  • Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
  • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
  • Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis.

    • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
    • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Pregnant or lactating patients.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03914612
Other Study ID Numbers  ICMJE NCI-2019-02186
NCI-2019-02186 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY018 ( Other Identifier: NRG Oncology )
NRG-GY018 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
URL: https://grants.nih.gov/policy/sharing.htm
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE NRG Oncology
Investigators  ICMJE
Principal Investigator: Ramez N Eskander NRG Oncology
PRS Account National Cancer Institute (NCI)
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP