Back to resultsA Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01
Primary Purpose
Cervical Cancer
Status
Not yet recruiting
Phase
Phase 1
Locations
India
Study Type
Interventional
Intervention
KRC-01
External Beam Radiation Therapy
cisplatin
brachytherapy
Sponsored by
About this trial
This is an interventional prevention trial for Cervical Cancer
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.
Sites / Locations
- Site 2
- Site 1
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
dose-escalation single arm
Arm Description
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)
Outcomes
Primary Outcome Measures
Adverse Events
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.
AEs of special interest
(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)
Physical examination
The physical examination will include:
General appearance
Head, eyes, ears, nose, and throat
Respiratory
Cardiovascular
Musculoskeletal
Abdomen
Neurologic
Extremities
Dermatologic
Lymphatic Partial examination, patient will verbally report changes since last week.
Tolerance
• Number of patients who have a significant treatment delays/interruption (total duration > 59 days)
Secondary Outcome Measures
Progression-free survival
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.
Overall survival
mortality rates
Disease-free survival
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.
Health-related quality of life (QOL)
European Organisation for Research and Treatment of Cancer (EORTC) QOL 30-Item Questionnaire (QLQ-C30) and EORTC 24-Item Cervical Cancer Questionnaire (QLQ-CX24)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05570422
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
January 30, 2027 (Anticipated)
Study Completion Date
March 30, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kortuc, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Phase 1 open label
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
dose-escalation single arm
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
KRC-01
Intervention Description
KRC-01 is a solution that contains hydrogen peroxide 3% with sodium hyaluronate 1%. Hydrogen peroxide is the active ingredient for this radiosensitizer.
Intervention Type
Radiation
Intervention Name(s)
External Beam Radiation Therapy
Intervention Description
Target definition for EBRT will be based on 3D imaging by computed tomography, positron emission tomography with computed tomography, or MRI.
Intensity-modulated radiotherapy (IMRT) must be used.
IMRT should be given once daily Monday-Friday, 5 fractions per week.
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
Chemotherapy
Intervention Description
Weekly concomitant cisplatin (40 mg/m2) during EBRT
Neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/m2) are not allowed.
Adjuvant chemotherapy (after completion of EBRT+BT) is not allowed.
Intervention Type
Radiation
Intervention Name(s)
brachytherapy
Intervention Description
BT treatment planning will be based on 3D-image-guided BT by MRI.
Low-dose-rate, pulsed-dose-rate, or high-dose-rate BT
Primary Outcome Measure Information:
Title
Adverse Events
Description
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.
Time Frame
36 month
Title
AEs of special interest
Description
(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)
Time Frame
36 month
Title
Physical examination
Description
The physical examination will include:
General appearance
Head, eyes, ears, nose, and throat
Respiratory
Cardiovascular
Musculoskeletal
Abdomen
Neurologic
Extremities
Dermatologic
Lymphatic Partial examination, patient will verbally report changes since last week.
Time Frame
at the time of Screening and at Week 6 and partial examination will be done weekly in between to document relevant changes.
Title
Tolerance
Description
• Number of patients who have a significant treatment delays/interruption (total duration > 59 days)
Time Frame
week 1 to 6
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
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.
Time Frame
: minimum 2 years, maximum 3 years
Title
Overall survival
Description
mortality rates
Time Frame
minimum 2 years, maximum 3 years
Title
Disease-free survival
Description
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.
Time Frame
minimum 2 years, maximum 3 years
Title
Health-related quality of life (QOL)
Description
European Organisation for Research and Treatment of Cancer (EORTC) QOL 30-Item Questionnaire (QLQ-C30) and EORTC 24-Item Cervical Cancer Questionnaire (QLQ-CX24)
Time Frame
minimum 2 years, maximum 3 years
Other Pre-specified Outcome Measures:
Title
CRT poor responder rate
Description
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
Time Frame
Out to Week 4 or 5
Title
Feasibility of hypoxia imaging
Description
Diffusion-weighted imaging-MRI (DWI-MRI) and Dynamic contrast-enhanced MRI (DCE-MRI)
Time Frame
Screening and after the completion of KRC-01 dosing (between Week 6 to Month 3).
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
females at birth currently with a cervix
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martine Francis
Phone
13013438894
Email
martine@mafinc.com
First Name & Middle Initial & Last Name or Official Title & Degree
Minako Koga
Phone
2026156004
Email
mkoga@kmphc.com
Facility Information:
Facility Name
Site 2
City
Chandigarh
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MArtine Francis
Phone
3013438894
Email
martine@mafinc.com
Facility Name
Site 1
City
Visakhapatnam
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martine Francis
Phone
3013438894
Email
martine@mafinc.com
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
undecided
Learn more about this trial
A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01
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