Clinical trial NCT05570422: A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Cervical Cancer
Lead sponsor: Kortuc, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-06
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1 open label
Primary purpose: PREVENTION

Brief summary: This is a seamless Phase 1/2 study consisting of two components. Phase 1 component is a dose-escalation, single arm, open label study in 10 patients to evaluate the safety and tolerability of KRC 01. Phase 2 component is a randomized, open label, controlled, multi-center study in 60 patients to evaluate the preliminary antitumor effect of KRC-01 in combination with CRT.

Detailed description: This is a seamless Phase 1/2 study consisting of two components. Phase 1 component is a dose-escalation, single arm, open label study in 10 patients to evaluate the safety and tolerability of KRC 01. Phase 2 component is a randomized, open label, controlled, multi-center study in 60 patients to evaluate the preliminary antitumor effect of KRC-01 in combination with CRT.

Phase 1 component (n=10) Phase 1 component is a dose-escalation single arm, open label study. All eligible subjects will receive external beam radiotherapy (EBRT) with cisplatin (40 mg/m2) intravenously (IV) once weekly for 5 weeks (sixth dose optional) followed by image-guided brachytherapy (BT).

KRC-01 will be dosed intratumorally within 2 hours prior to EBRT starting from second week of EBRT.

There are two cohorts (n=5 per cohort) Cohort 1: Once-a-week between Monday to Thursday (not necessarily the same day every week) Cohort 2: Twice-a-week with a 1- or 2- day interval (either Mon+Wed, Mon+Thu, or Tue+Thu)

After 5 subjects of Cohort 1 have completed CRT+BT, the safety review committee (SRC) will evaluate the safety and tolerability of KRC-01 once-a-week dosing and determine Go/ No Go decision to Cohort 2 (twice-a-week dosing).

After all 10 subjects have completed CRT+BT, the SRC will evaluate the safety and tolerability of KRC 01 and determine Go/ No Go decision to Phase 2 component with optimal dosing regimen.

Phase 2 component (n=60) Phase 2 component is a randomized, open label study. All eligible subjects will be randomized to Standard of care (SOC) group or SOC with KRC-01 group.

All subjects will receive EBRT with cisplatin (40 mg/m2) IV once-a-week for 5 weeks (sixth dose optional) followed by image-guided BT. Only for KRC-01 group, KRC-01 will be dosed intratumorally at the optimal dosing schedule selected in Phase 1 component within 2 hours prior to EBRT starting from second week of EBRT.

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.

Primary outcomes:
measure: Adverse Events
timeFrame: 36 month
measure: AEs of special interest
timeFrame: 36 month
measure: Physical examination
timeFrame: at the time of Screening and at Week 6 and partial examination will be done weekly in between to document relevant changes.
measure: Tolerance
timeFrame: week 1 to 6
Secondary outcomes:
measure: Progression-free survival
timeFrame: : minimum 2 years, maximum 3 years
measure: Overall survival
timeFrame: minimum 2 years, maximum 3 years
measure: Disease-free survival
timeFrame: minimum 2 years, maximum 3 years
measure: Health-related quality of life (QOL)
timeFrame: minimum 2 years, maximum 3 years
Other outcomes:
measure: CRT poor responder rate
timeFrame: Out to Week 4 or 5
measure: Feasibility of hypoxia imaging
timeFrame: Screening and after the completion of KRC-01 dosing (between Week 6 to Month 3).
Locations:
city: Chandigarh
country: India
facility: Site 2
city: Visakhapatnam
country: India
facility: Site 1
city: Bangkok
country: Thailand
facility: Site 5
city: Chiang Mai
country: Thailand
facility: Site 4
city: Manchester
country: United Kingdom
facility: Site 3
Study officials:
References: