A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy of KRC-01
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| ClinicalTrials.gov Identifier: NCT05570422 |
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Recruitment Status :
Not yet recruiting
First Posted : October 6, 2022
Last Update Posted : March 8, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cervical Cancer | Drug: KRC-01 Radiation: External Beam Radiation Therapy Drug: cisplatin Radiation: brachytherapy | Phase 1 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 70 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Phase 1 open label |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| 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 |
| Estimated Study Start Date : | April 1, 2024 |
| Estimated Primary Completion Date : | January 30, 2027 |
| Estimated Study Completion Date : | March 30, 2027 |
| Arm | Intervention/treatment |
|---|---|
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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) |
Drug: KRC-01
KRC-01 is a solution that contains hydrogen peroxide 3% with sodium hyaluronate 1%. Hydrogen peroxide is the active ingredient for this radiosensitizer. Radiation: External Beam Radiation Therapy
Drug: cisplatin
Other Name: Chemotherapy Radiation: brachytherapy
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- 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.
- 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)
- 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:
- 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 [ Time Frame: week 1 to 6 ]• Number of patients who have a significant treatment delays/interruption (total duration > 59 days)
- 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.
- Overall survival [ Time Frame: minimum 2 years, maximum 3 years ]mortality rates
- 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.
- 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)
- 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
- 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)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Gender Based Eligibility: | Yes |
| Gender Eligibility Description: | females at birth currently with a cervix |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05570422
| Contact: Martine Francis | 13013438894 | martine@mafinc.com | |
| Contact: Minako Koga | 2026156004 | mkoga@kmphc.com |
| India | |
| Site 2 | |
| Chandigarh, India | |
| Contact: Martine Francis 13013438894 martine@mafinc.com | |
| Site 1 | |
| Visakhapatnam, India | |
| Contact: Martine Francis 3013438894 martine@mafinc.com | |
| Thailand | |
| Site 5 | |
| Bangkok, Thailand | |
| Contact: Martine Francis 13013438894 martine@mafinc.com | |
| Contact: Minako Koga 2026156004 mkoga@kmpc.com | |
| Site 4 | |
| Chiang Mai, Thailand | |
| Contact: Martine Francis 13013438894 martine@mafinc.com | |
| Contact: Minako Koga 202-615-6004 mkoga@kmpc.com | |
| United Kingdom | |
| Site 3 | |
| Manchester, United Kingdom | |
| Contact: Martine Francis 13013438894 martine@mafinc.com | |
| Contact: Minako Koga 202-615-6004 mkoga@kmpc.com | |
| Responsible Party: | Kortuc, Inc. |
| ClinicalTrials.gov Identifier: | NCT05570422 |
| Other Study ID Numbers: |
KRC-01-C01 |
| First Posted: | October 6, 2022 Key Record Dates |
| Last Update Posted: | March 8, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Uterine Cervical Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Cervical Diseases Uterine Diseases |
Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Diseases Cisplatin Antineoplastic Agents |