Testing the addition of the immunotherapy drug pembrolizumab to the usual chemotherapy treatment (paclitaxel and carboplatin) in endometrial cancer

JRCT ID: jRCT2031210512

Registered date:25/12/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Endometrial Cancer
• Date of first enrollment: 08/02/2022
• Target sample size: 60
• Countries of recruitment: USA,Japan,Canada,Japan,Korea,Japan
• Study type: Interventional

Intervention(s)

Arm 1
Combination Phase: Placebo 200 mg IV Day 1, Paclitaxel 175mg/m2 IV over 3 hours Day 1, Carboplatin AUC 5 IV Day 1. Every 3 weeks x 6 cycles
Maintenance Phase: Placebo 400 mg IV Day 1. Every 6 weeks x up to 14 cycles

Arm 2
Combination Phase: Pembrolizumab (MK-3475) 200 mg IV Day 1, Paclitaxel 175mg/m2 IV over 3 hours Day 1,
Carboplatin AUC 5 IV Day 1. Every 3 weeks x 6 cycles
Maintenance Phase:Pembrolizumab (MK-3475) 400 mg IV Day 1. Every 6 weeks x up to 14 cycles

One cycle= 3 weeks for the combination phase
One cycle = 6 weeks for maintenance phase

Maximum number of cycles (combination phase + maintenance phase) = 20

Outcome(s)

• Primary Outcome: Progression-free survival (PFS)

Secondary Outcome

1. Incidence of adverse events
2. Objective tumor response (ORR)
3. Duration of objective response (DOR)
4. Overall survival (OS)
5. Quality of life (QoL) and patient-reported outcomes (PROs)
6. Incidence of pembrolizumab treatment and self-reported neurotoxicity
7. Concordance between Institutional Mismatch repair (MMR) immunohistochemistry (IHC) testing and centralized MMR IHC
8. Effect of pembrolizumab on PFS and OS by PD-L1 IHC
9. Association between Program Death Ligand 1 (PD-L1) IHC and MMR status

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

1. Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer. 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.).
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.
3. Prior Therapy
- 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.
4. Age >=18
5. Performance Status of 0, 1 or 2
6. Adequate hematologic function defined as follows:
- Platelets >= 100,000/mcl
- Absolute neutrophil count (ANC) >= 1,500/mcl
7. Adequate renal function defined as follows:
Creatinine <= 1.5 x institutional/laboratory upper limit of normal (ULN).
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
9. TSH within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy).
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.
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.
12. 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.
13. 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.
14. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the U.S., authorization permitting release of personal health information.

Exclude criteria

1. Patients with prior treatment with anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.
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.
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.
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.
- 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.
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.
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.
7. Patients who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
8. Uncontrolled intercurrent illness including.
9. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis.
10. Pregnant or lactating patients.

Related Information

• Primary Sponsor: Fujiwara Keiichi
• Secondary Sponsor: NRG Oncology / National Cancer Institute
• Secondary ID(s): NCT03914612