Pembrolizumab with carbon-ion radiotherapy for cervical adenocarcinoma

JRCT ID: jRCTs031240651

Registered date:31/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Cervical cancer
• Date of first enrollment: 31/01/2025
• Target sample size: 45
• Study type: Interventional

Intervention(s)

The treatment includes carbon-ion radiotherapy (CIRT), image-guided brachytherapy, cisplatin, and pembrolizumab.
Patients received CIRT daily for 4 days each week. The patient was positioned on the treatment couch with the immobilization devices at every treatment session. The dose to whole pelvis is fixed at 36.0 Gy (RBE) in 12 fractions over 3 weeks. The dose to the cervical tumor and the positive lymph node was fixed at 19.2 Gy (RBE) in 4 fractions over 1 week. Thus, the total dose to the cervical tumor and the positive lymph node is 55.2 Gy (RBE) in 16 fractions over 4 weeks. Following C-ion RT, three sessions of high-dose rate brachytherapy were performed twice per week using an Ir-192 Remote afterloading system at each facility participating in the study. Tandem and ovoid applicators with or without interstitial needles are used.
Five courses of weekly cisplatin at a dose of 40 mg/m2 (maximum dose of 70 mg/body) should be given during the CIRT and brachytherapy period. In principle, the first course of cisplatin should be administered on day 1 of CIRT. Cisplatin was administrated on a different day during the brachytherapy period.
Patients receive 2 cycles of pembrolizumab 200 mg every 3 weeks plus chemo-CIRT, followed by 17 cycles of pembrolizumab 400 mg every 6 weeks. Pembrolizumab should be administered intravenously and will be given for a total of 2 years.

Outcome(s)

• Primary Outcome: 2-year progression-free survival
• Secondary Outcome: 2-year overall survival (OS), complete response (CR) rate, 2-year local control (LC), acute and late toxicities

Key inclusion & exclusion criteria

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

Include criteria

1.Female participants who are at least 18 years of age on the day of signing informed consent
2.Histologically confirmed adenocarcinoma or adenosquamous carcinoma of the uterine cervix
3.Stage IIA2, IIB, IIIA, IIIB, IIIC1r, IVA by FIGO classification (2018)
4.The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
5.Have measurable disease based on RECIST 1.1.
6.Archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated has been provided.
NOTE: Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
7.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. NOTE: Evaluation of ECOG is to be performed within 7 days prior to the first administration of the pembrolizumab.
8.Have adequate organ function as defined in the following.
NOTE: All clinical laboratory tests in the screening phase should be performed within 7 days prior to the first administration of the pembrolizumab.

Hematological
Absolute neutrophil count (ANC) >=1500/uL
Platelets >=100,000/uL
Hemoglobin >=9.0 g/dL or >=5.6 mmol/L

Renal
Creatinine clearance (CCr)
(CCr is estimated by Cockcroft-Gault equation
Hepatic
Total bilirubin <=1.5 times ULN OR direct bilirubin <=ULN for participants with total bilirubin levels >1.5 times ULN
AST (GOT) and ALT (GPT) <=2.5 times ULN (<=5 times ULN for participants with liver metastases)

Coagulation
International normalized ratio (INR) OR prothrombin time (PT)
Activated partial thromboplastin time (aPTT) <=1.5 times ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.

Exclude criteria

1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another T-cell receptor (e.g., CTLA-4, OX-40, CD137).
2. Has received prior radical surgery, RT, or systemic therapy (including investigational drugs) for cervical cancer. Note: Conization for localized cervical tumors is allowed.
3. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
4. Has received an investigational agent or has used an investigational device within 4 weeks prior to pembrolizumab administration.
5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
6. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
7. Has severe hypersensitivity (>= Grade 3) to pembrolizumab and/or any of its excipients.
8. Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g.., thyroxine, insulin, or physiologic corticosteroid).
9. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
10. Has an active infection requiring systemic therapy.
11. History of active Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
15. Has had an allogenic tissue/solid organ transplant.
16. History of HIV infection.

Related Information

• Primary Sponsor: Ohno Tatsuya
• Source(s) of Monetary Support: MSD Corporation