KRC-01 added to chemoradiation for stage II-III cervical cancer

A Phase 1/2 Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01 Intratumoral Injection Combined With Radiotherapy in Patients With Locally Advanced Cervical Cancer

This will try injecting KRC-01 into the tumor alongside standard chemoradiation in women with stage II-III cervical cancer to see if it is safe and helps shrink tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Kortuc, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 4 sites (Chandigarh and 3 other locations)
• Trial ID: NCT05570422 on ClinicalTrials.gov

What this trial studies

This seamless Phase 1/2 trial begins with a Phase 1, open-label dose-escalation cohort of 10 patients to test safety and tolerability of intratumoral KRC-01 given during external beam radiotherapy (EBRT) with weekly cisplatin and subsequent brachytherapy. Phase 1 compares once-weekly versus twice-weekly intratumoral dosing in two small cohorts with safety review committee decisions guiding escalation and progression to Phase 2. The Phase 2 component will randomize about 60 patients across multiple centers to receive KRC-01 plus chemoradiation versus chemoradiation alone to measure preliminary antitumor effect. Tumor response will be measured by RECIST v1.1 and enrollment requires tumors ≥5 cm that are accessible for intratumoral injection.

Who should consider this trial

Good fit: Women aged 18 or older with FIGO stage II or III squamous, adenocarcinoma, or adenosquamous cervical cancer, no metastatic disease, no prior chemo/radiation, ECOG 0-1, and at least one tumor ≥5 cm that is accessible for intratumoral injection and planned for EBRT with weekly cisplatin and brachytherapy.

Not a fit: Patients with metastatic disease, prior pelvic chemotherapy or radiotherapy, tumors <5 cm or not accessible for injection, poor performance status, or a life expectancy under three months are unlikely to be eligible or receive benefit from this protocol.

Why it matters

Potential benefit: If successful, adding KRC-01 could improve tumor shrinkage and local disease control when combined with standard chemoradiation without unacceptable additional toxicity.

How similar studies have performed: Intratumoral radiosensitizers and local biologic agents have been explored in early-phase studies with limited and mixed results, so this approach remains experimental and preliminary.

Eligibility criteria

Inclusion Criteria:

* Provide written informed consent before participation.
* Female subjects age 18 years or older.
* Histologically diagnosed squamous cell carcinoma, adenocarcinoma or adeno-squamous cell carcinoma of the uterine cervix.
* FIGO stage II and III locally advanced cervical cancer.
* No evidence of metastatic disease.
* At least one tumor that qualifies as a Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 tumor with tumor size \>5 cm diameter, not previously irradiated, at baseline assessed \[by magnetic resonance imaging (MRI)\] within 28 days before Day 1.
* No prior chemotherapy or radiotherapy for cervical cancer.
* Intention to undergo treatment including EBRT with 5 cycles of cisplatin followed by BT; to be completed within 8 weeks of its initiation.
* Patients with predicted life expectancy of 3 months or more.
* Target tumor is accessible for intratumoral injection.
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
* Negative pregnancy test before start of CRT in women of childbearing potential and an ability/willingness to protect against pregnancy from consent and for 3 months post-RT.

Exclusion Criteria:

* Other primary malignancies except basal cell carcinoma of the skin.
* Histologically diagnosed small cell (neuroendocrine), melanoma, clear cell and other rare variants of the classical adenocarcinoma at cervices.
* Previous pelvic or abdominal radiotherapy.
* Previous total or partial hysterectomy.
* Combination of preoperative radiotherapy with surgery.
* Patients receiving neo-adjuvant chemotherapy or non-protocol antineoplastic treatment apart from weekly cisplatin (40 mg/m2).
* Anatomical location and/or extent of disease difficult to access for safe intratumoral drug injections.
* Contraindications to the pelvic radiation such as inflammatory bowel disease and collagen vascular disease.
* Contraindications to MRI.
* Patients on anticoagulants or deranged coagulation profile.
* Pregnancy or nursing.
* High medical risks because of non-malignant systemic disease or with active uncontrolled infection.
* Participation in another clinical trial with an investigational drug, device or biologic within the preceding 3 months, except an observational study.

Where this trial is running

Chandigarh and 3 other locations

• Site 2 — Chandigarh, India (Not_yet_recruiting)
• Site 5 — Bangkok, Bangkok, Thailand (Recruiting)
• Site 4 — Chiang Mai, Thailand (Recruiting)
• Site 3 — Manchester, United Kingdom (Not_yet_recruiting)

Study contacts

• Study coordinator: Martine Francis

Conditions Cervical Cancer