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
- Conditions
- Neoplasms
- Registration Number
- KCT0006980
- Lead Sponsor
- Korea Cancer Center Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- Female
- Target Recruitment
- 810
3.2.1 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. (This requirement does not apply to sites in Japan.) (08-DEC-2020)
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.). (07/03/2019)
Submission of tumor specimens for centralized MMR IHC testing is required after Step 1 and before Step 2 registration. (See Section 5.7 and 10.2 for details.)
3.2.2 In patients with measurable disease, lesions will be defined and monitored by RECIST 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 CT or MRI. Lymph nodes must be = 15 mm in short axis when measured by CT or MRI. (21-MAY-2021)
3.2.3 Prior Therapy: (09/24/2019) (07-FEB-2020)
• 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.
3.2.4 Age = 18
3.2.5 Performance Status of 0, 1 or 2 (see Appendix II) (07/03/2019)
3.2.6 Adequate hematologic function defined as follows:
• Platelets = 100,000/mcl
• Absolute neutrophil count (ANC) = 1,500/mcl
3.2.7 Adequate renal function defined as follows: (07/03/2019)
Creatinine = 1.5 x institutional/laboratory upper limit of normal (ULN).
3.2.8 Adequate hepatic function defined as follows:
• Total serum bilirubin level = 1.5 x ULN (patients with known Gilbert’s disease who have bilirubin level = 3 x ULN may be enrolled)
• AST and ALT = 3 x ULN
3.2.9 TSH within normal limits (TSH 3.2.10 HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 2 registration are eligible for this trial.
3.2.11 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. (07- FEB-2020)
3.2.12 Administration of study drugs (pembrolizumab [MK-3475], paclitaxel, carboplatin) may have an adverse effect on pregnancy and poses a risk to the human fetus
3.3.1 Patients with prior treatment with anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.
3.3.2 Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or pembrolizumab (MK-3475) and/or its excipients; and/or a severe hypersensitivity reaction to paclitaxel and/or carboplatin. (07/03/2019) (21-MAY-2021)
3.3.3 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. (07-FEB-2020)
3.3.4 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 (07-FEB-2020)
• 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.
3.3.5 Patients with treated brain metastases are eligible if follow-up brain imaging after 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. (07-FEB-2020)
3.3.6 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 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, Sjögren’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.
3.3.7 Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
3.3.8 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. (09/24/2019)
3.3.9 Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and c
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-Free Survival(PFS)
- Secondary Outcome Measures
Name Time Method Adverse events as assessed by CTCAE.;Objective tumor response as assessed by RECIST 1.1.;Duration of objective response ;Overall Survival(OS);Quality of life (QOL) and patient-reported outcomes (PROs), measured by the FACT-En- TOI, the FACT/GOG-Ntx subscale (short), PROMIS-Fatigue (short form),the PROMIS- physical function (short form) and a single-item measuring bother from side effects of cancer therapy.;Pembrolizumab (MK-3475) treatment and self-reported neurotoxicity with FACT/GOG- Ntx.;Concordance between institutional MMR IHC testing and centralized MMR IHC.;The effect of pembrolizumab (MK-3475) on PFS and OS by PD-L1 IHC (combined positive score (CPS)) within pMMR and dMMR populations.;Measures of association between PD-L1 IHC (CPS) and MMR status.