- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05570422
A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Minako Koga
- Phone Number: 2026156004
- Email: mkoga@kmphc.com
Study Contact Backup
- Name: Martine Francis
- Phone Number: 13013438894
- Email: martine@mafinc.com
Study Locations
-
-
-
Chandigarh, India
- Site 2
-
Contact:
- Martine Francis
- Phone Number: 13013438894
- Email: martine@mafinc.com
-
Visakhapatnam, India
- Site 1
-
Contact:
- Martine Francis
- Phone Number: 3013438894
- Email: martine@mafinc.com
-
-
-
-
-
Bangkok, Thailand
- Site 5
-
Contact:
- Martine Francis
- Phone Number: 13013438894
- Email: martine@mafinc.com
-
Contact:
- Minako Koga
- Phone Number: 2026156004
- Email: mkoga@kmpc.com
-
Chiang Mai, Thailand
- Site 4
-
Contact:
- Martine Francis
- Phone Number: 13013438894
- Email: martine@mafinc.com
-
Contact:
- Minako Koga
- Phone Number: 202-615-6004
- Email: mkoga@kmpc.com
-
-
-
-
-
Manchester, United Kingdom
- Site 3
-
Contact:
- Martine Francis
- Phone Number: 13013438894
- Email: martine@mafinc.com
-
Contact:
- Minako Koga
- Phone Number: 202-615-6004
- Email: mkoga@kmpc.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: dose-escalation single arm
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) |
KRC-01 is a solution that contains hydrogen peroxide 3% with sodium hyaluronate 1%.
Hydrogen peroxide is the active ingredient for this radiosensitizer.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events
Time Frame: 36 month
|
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a study drug that does not necessarily have a causal relationship with the treatment.
|
36 month
|
AEs of special interest
Time Frame: 36 month
|
(local pain, radiation dermatitis, tumor lysis syndrome, superficial soft tissue fibrosis, vaginal stenosis, gastrointestinal/urinary AEs, and severe and medically significant bleeding (requires urgent intervention) after intratumoral injection)
|
36 month
|
Physical examination
Time Frame: at the time of Screening and at Week 6 and partial examination will be done weekly in between to document relevant changes.
|
The physical examination will include:
|
at the time of Screening and at Week 6 and partial examination will be done weekly in between to document relevant changes.
|
Tolerance
Time Frame: week 1 to 6
|
• Number of patients who have a significant treatment delays/interruption (total duration > 59 days)
|
week 1 to 6
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival
Time Frame: : minimum 2 years, maximum 3 years
|
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first.
Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions.
In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm.
The appearance of one or more new lesions is also considered PD.
Unequivocal progression of non-target lesions is also considered PD.
|
: minimum 2 years, maximum 3 years
|
Overall survival
Time Frame: minimum 2 years, maximum 3 years
|
mortality rates
|
minimum 2 years, maximum 3 years
|
Disease-free survival
Time Frame: minimum 2 years, maximum 3 years
|
Disease progression can be considered as a worsening of a patient's condition attributable to the disease for which the investigational product is being studied. It may be an increase in the severity of the disease under study and/or increases in the symptoms of the disease. An event can be attributed to disease progression even without radiological or biomarker evidence of disease progression. Deterioration of the disease under study and associated symptoms or findings, including the development of new, or the progression of existing, metastases, should not be regarded as an AE, unless the study medication is considered to have contributed to the progression. |
minimum 2 years, maximum 3 years
|
Health-related quality of life (QOL)
Time Frame: minimum 2 years, maximum 3 years
|
European Organisation for Research and Treatment of Cancer (EORTC) QOL 30-Item Questionnaire (QLQ-C30) and EORTC 24-Item Cervical Cancer Questionnaire (QLQ-CX24)
|
minimum 2 years, maximum 3 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CRT poor responder rate
Time Frame: Out to Week 4 or 5
|
Poor responder is defined as 40 cc residual tumor at Week 4 or Week 5 assessed by MRI T2) in patients who have > 40cc tumor at the baseline
|
Out to Week 4 or 5
|
Feasibility of hypoxia imaging
Time Frame: Screening and after the completion of KRC-01 dosing (between Week 6 to Month 3).
|
Diffusion-weighted imaging-MRI (DWI-MRI) and Dynamic contrast-enhanced MRI (DCE-MRI)
|
Screening and after the completion of KRC-01 dosing (between Week 6 to Month 3).
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Antineoplastic Agents
- Cisplatin
Other Study ID Numbers
- KRC-01-C01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cervical Cancer
-
University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
-
M.D. Anderson Cancer CenterWithdrawnStage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical Cancer FIGO 2018 | Stage IIB Cervical Cancer FIGO 2018 | Stage III Cervical Cancer FIGO 2018 | Stage IIIA Cervical Cancer FIGO... and other conditions
-
Abramson Cancer Center of the University of PennsylvaniaWithdrawnCervical Cancer | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingCervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Recurrent Cervical Carcinoma | Stage IB3 Cervical Cancer FIGO 2018 | Stage II Cervical Cancer FIGO 2018 | Stage IIA Cervical Cancer FIGO 2018 | Stage IIA1 Cervical Cancer FIGO 2018 | Stage IIA2 Cervical... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IA Cervical Cancer | Stage IB Cervical Cancer | Stage IA1 Cervical Cancer | Stage IA2 Cervical Cancer | Stage IB1 Cervical Cancer | Stage IB2 Cervical Cancer | Stage IB3 Cervical CancerUnited States
-
Shanghai First Maternity and Infant HospitalNot yet recruitingCervical Cancer, Stage IIB | Cervical Cancer Stage IIIB | Cervical Cancer Stage IIIA | Cervical Cancer, Stage IVA
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Cervical Cancer | Stage IVA Cervical Cancer | Stage IVB Cervical Cancer | Stage IIIA Cervical Cancer | Stage IIIB Cervical CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Squamous Cell Carcinoma | Stage IB Cervical Cancer | Stage IIA Cervical Cancer | Stage IIB Cervical Cancer | Stage III Cervical Cancer | Stage IVA Cervical CancerUnited States
-
Institut de Cancérologie de LorraineCompletedCervical Adenocarcinoma | Stage IB Cervical Cancer | Stage III Cervical Cancer | Stage II Cervical CancerFrance
Clinical Trials on KRC-01
-
Livzon Pharmaceutical Group Inc.Active, not recruiting
-
Zucara Therapeutics Inc.RecruitingType 1 Diabetes Mellitus With HypoglycemiaUnited States, Canada
-
Ixchelsis LimitedCompletedPremature EjaculationUnited States
-
Enterin Inc.TerminatedParkinson Disease | ConstipationUnited States
-
Shanghai Hongyitang Biopharmaceutical Technology...Completed
-
Zhongmou TherapeuticsRecruitingX-linked RetinoschisisChina
-
BioPharmX, Inc.CompletedAcne VulgarisUnited States
-
Enterin Inc.CompletedParkinson Disease | ConstipationUnited States
-
Hokkaido University HospitalJapan Agency for Medical Research and DevelopmentRecruiting
-
Valerio TherapeuticsRecruitingBreast Cancer | Prostate Cancer | Advanced or Metastatic Solid Tumors | Recurrent Ovarian CancerUnited States