Dostarlimab with cisplatin, etoposide, and radiotherapy for small cell neuroendocrine cervical cancer

Dostarlimab, Cisplatin and Etoposide in Combination With Radiotherapy in Sandwich Sequence for Small Cell Neuroendocrine Cervical Carcinoma (DICER Trial): Taiwanese Gynecologic Oncology Group (TGOG) 1012

This trial will test whether adding the immunotherapy drug dostarlimab to cisplatin/etoposide chemotherapy plus radiotherapy helps women with small cell neuroendocrine cervical carcinoma stay progression-free longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 20 Years to 70 Years
• Sex: Female
• Sponsor: Chang Gung Memorial Hospital (other)
• Drugs / interventions: dostarlimab, prednisone
• Locations: 1 site (Taoyuan, Taiwan)
• Trial ID: NCT07336147 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center trial adds the anti–PD-1 antibody dostarlimab to standard cisplatin and etoposide chemoradiation using a 'sandwich' sequencing around radiotherapy for previously untreated small cell neuroendocrine cervical carcinoma. Eligible participants provide archival or fresh tumor tissue and receive combined chemoimmunotherapy together with external beam radiotherapy per protocol. The primary aim is to compare progression-free survival to historical controls treated with chemoradiation alone, while systematically monitoring safety and tolerability. The study is conducted at Chang Gung Memorial Hospital, Linkou Branch.

Who should consider this trial

Good fit: Women aged 20–70 with previously untreated small cell neuroendocrine cervical carcinoma (IB1 with LVSI through IV, including limited oligometastasis of one distant organ with up to two nodules) who can provide tumor tissue, are not pregnant or breastfeeding, and can receive combined chemotherapy, immunotherapy, and radiotherapy are ideal candidates.

Not a fit: Patients with widespread metastatic disease (more than one organ or more than two nodules), prior treatment for this cancer, or contraindications to immunotherapy or radiotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could extend progression-free survival and reduce the risk of recurrence compared with chemoradiation alone.

How similar studies have performed: Checkpoint inhibitors combined with chemotherapy or radiotherapy have shown benefit in other cancer types, but this exact approach in small cell neuroendocrine cervical carcinoma is novel with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Female participants who are 20-70 years of age on the day of signing informed consent with histologically confirmed diagnosis of Previously untreated SCNECC IB2-IV or IB1 with LVSI or IVB with oligometastasis (only in one distant organ not more than 2 nodules which can be encompassed by RT) will be enrolled in this study.

   \*A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
   2. A WOCBP who agrees to participate this trial should be informed that after the protocol treatment the ovarian function and child-bearing potential will be permanently lost and she has to follow the contraceptive guidance in Appendix 3 after enrollment through neoadjuvant chemoimmuntherapy period till external beam radiotherapy (EBRT) commences.
2. Have provided archival tumor tissue sample or newly obtained biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archival tissue. At least 5 punch biopsiesdof 3mm in diameter.
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

   Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy for SCNECC including investigational agents prior to enrollment.
4. Has received prior pelvic radiotherapy.
5. Has received radical surgery for cervical cancer.
6. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
8. 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 study drug.
9. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
10. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
11. Has severe hypersensitivity (≥Grade 3) to dostarlimab and/or any of its excipients.
12. Participant has an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
13. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
14. Has an active infection requiring systemic therapy.
15. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
16. Has a known history of untreated Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus infection (for those with anti-HCV+, patients who ever HCV RNA positive should undergo 8-12 weeks direct acting agents (DAA) treatment and confirmed with HCV cure, defined as HCV RNA negative at week 12 post end-of-treatment). Note: Testing for Hepatitis B and Hepatitis C is required but the patient is eligible if well controlled.
17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
18. Allergy: Participant cannot have history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies or fusion proteins, sensitivity to any of the study treatments or components thereof, or a history of drug or other allergy that contraindicates their participation.
19. Has had an allogenic tissue/solid organ transplant.
20. Participant has received a live vaccine within 30 days of planned start of study therapy. COVID-19 vaccines that do not contain live viruses are allowed. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live.
21. Participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.

Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.

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Where this trial is running

Taoyuan, Taiwan

• Chang Gung Memorial Hospital, Linkou Branch — Taoyuan, Taiwan, Taiwan (RECRUITING)

Study contacts

• Study coordinator: CHYONG-HUEY CHL LAI

Conditions: Female, dostarlimab, cisplatin, etoposide, cervical carcinoma