Evaluation of Safety and Tolerability of KAND567 and Carboplatin in Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
- Trial ID
- 2024-515572-13-00
- Protocol
- KAN0007
- Sponsor
- Kancera AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of KAND567 in combination with **carboplatin** therapy, and to determine the Recommended Phase II Dose (RPIID) of KAND567 in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. This is clinically relevant as it aims to establish a safe and effective dosage regimen for KAND567, potentially improving therapeutic outcomes for patients with these recurrent cancers.
Secondary objectives include:
- Evaluating the Overall Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions.
- Assessing signs of anti-tumor activity of KAND567 in combination with carboplatin therapy.
- Determining the plasma exposure of KAND567.
- Assessing the effect on pain symptoms of KAND567 in combination with carboplatin therapy.
Participants
The clinical trial involves a study population exclusively comprising **female** participants, as the trial is focused on recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. The age range of participants is not specified, but they must be at least 18 years old. The trial does not include a vulnerable population. Participants are required to have a life expectancy of at least 12 weeks and must have a history of platinum-based chemotherapy in the first-line setting. The trial population was selected based on specific inclusion criteria, including histologically verified high-grade serous or high-grade endometrioid epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Participants must have recurrent disease, defined as a relapse within a specified timeframe after previous platinum-containing treatment. Adequate organ function is required, and participants must be able to take oral medications. The sponsor has not provided information on the total number of participants. Lifestyle considerations such as diet and physical activity are not detailed in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the safety and tolerability of **KAND567** in combination with **carboplatin** therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. This study is structured as a two-part, open-label, multicenter trial with a dose escalation phase followed by an expansion cohort. The trial is categorized as a Phase Ib/IIa study, with the primary objective of determining the Recommended Phase II Dose (RPIID) of KAND567. The trial is expected to run from November 9, 2023, to December 4, 2024, with recruitment starting on March 18, 2024, and ending on November 12, 2024.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as histologically verified high-grade serous or endometrioid epithelial ovarian cancer, age, and organ function. Follow-up visits will occur at regular intervals to monitor safety endpoints, including the occurrence of adverse events, serious adverse events, and dose-limiting toxicities. The primary endpoints focus on safety parameters, while secondary endpoints include overall response rate, progression-free survival, and overall survival. The end-of-study visit will conclude the participant's involvement, which is expected to last until the trial's completion in June 2025.
Participants are required to comply with study procedures, including the use of adequate birth control methods and the provision of informed consent. Conditions that may lead to early termination from the study include non-compliance with study protocols or the occurrence of significant adverse events. The trial's design ensures a rigorous evaluation of the investigational product's safety and efficacy, contributing valuable data to the field of oncology.
Treatment
The clinical trial involves the administration of **Carboplatin**, a chemotherapeutic agent, in various formulations. The primary formulation used is "Carboplatin Accord 10 mg/ml koncentrat till infusionsvätska, lösning," which is a **solution for infusion**. This formulation is administered via **intravenous use**. The dosage and frequency of administration are determined based on the specific protocol of the trial, which aims to evaluate the safety and tolerability of the combination therapy in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. The **Carboplatin** used in this trial is of chemical origin, and its administration is closely monitored to ensure participant compliance and safety.
Another formulation used in the trial is "Carboplatin Actavis 10 mg/ml koncentrat till infusionsvätska, lösning," which is also a **solution for infusion** administered intravenously. This formulation shares the same active substance, **Carboplatin**, and is utilized to assess its efficacy and safety in combination with other treatments. The trial protocol specifies the dosing schedule, and participant compliance is monitored through regular assessments and follow-ups.
The trial also includes the use of "Carboplatin Ebewe 10 mg/ml koncentrat till infusionsvätska, lösning," another **solution for infusion** administered intravenously. This formulation is part of the chemotherapeutic regimen being evaluated for its potential benefits in treating the specified cancer types. The administration of this formulation follows a structured dosing schedule, and adherence to the protocol is ensured through systematic monitoring.
In addition to the **Carboplatin** formulations, the trial involves the experimental medication "KAND567 capsule," a **fractalkine receptor antagonist**. This medication is provided in a **capsule, hard** form and is administered orally. The trial aims to determine the Recommended Phase II Dose (RPIID) of KAND567 in combination with **Carboplatin** therapy. The dosing schedule for KAND567 is carefully designed to optimize its therapeutic potential while minimizing adverse effects. Participant compliance with the oral administration is monitored through regular check-ins and assessments.
Throughout the trial, the administration of these medications is conducted under strict clinical guidelines to ensure the safety and well-being of the participants. The trial's design includes comprehensive monitoring of drug administration, adherence to dosing schedules, and participant compliance to achieve reliable and valid results.
Efficacy
The efficacy of the clinical trial will be assessed using several key endpoints. Primary endpoints include the occurrence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs). The safety endpoint parameters will be evaluated based on the frequency and severity of AEs, vital signs, electrocardiography (ECG), and the results of laboratory safety tests and urinalysis. Additionally, the Recommended Phase II Dose (RPIID) of KAND567 in combination with **carboplatin** therapy will be determined based on safety and tolerability in Part 1 (Phase Ib) of the study.
Secondary endpoints will include the Overall Response Rate (ORR) at Weeks 12 and 18, according to RECIST 1.1 and GCIG definitions, which will assess the best overall response in subjects with measurable disease or without measurable disease evaluable by CA 125. Progression-free survival (PFS) and overall survival (OS) will be measured at Weeks 12 and 18 and at the end of the study, respectively. The Disease Control Rate (DCR), which includes complete response (CR), partial response (PR), and stable disease (SD), will also be evaluated at Weeks 12 and 18. The duration of response will be assessed according to RECIST 1.1 and GCIG definitions, measuring the time from documentation of tumor response to disease progression. Additionally, KAND567 pharmacokinetic (PK) drug concentration data will be graphically visualized, and changes in pain score will be measured using the Numeric Rating Scale (NRS) from baseline (Week 1) to Weeks 4, 7, 10, 13, 16, and 20.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Histologically verified high-grade serous or high-grade endometrioid epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer.
- Participants* must have recurrent disease, defined as: 1st relapse 3 to 6 months after completion of the last dose of primary platinum containing treatment, or 2nd or 3rd relapse within 6 months after completion of the last dose of the latest platinum-containing regimen (platinum-free interval within 6 months). *Prior treatment with PARPi is allowed. In bevacizumab-naive patients, bevacizumab can be included as part of treatment after tumor progression on study drugs according to local clinical practice.
- Participants must have had platinum-based chemotherapy in the first-line setting (primary treatment or 1st relapse requiring chemotherapy).
- For BRCA status, samples must be available for analysis; for HRD status, samples should be available for analysis, if possible. If not already analyzed, the subject agrees to undergo analysis of HRD and BRCA status on primary tumor tissue and/or recurrent tumor tissue.
- ECOG performance status 0-2.
- Subjects must have at least 1 measurable disease or non-measurable disease according to RECIST 1.1 guidelines. Non-measurable disease must be evaluable using GCIG CA 125 criteria (CA 125 ≥ 2 x upper limit of normal [ULN]). If the subject has only 1 measurable lesion, this should not be the same lesion used for biopsy, nor should it be in a previously irradiated area.
- Able to take oral medications.
- Adequate organ function: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin ≥ 80 g/dl, Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula, Total bilirubin ≤ ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ ULN.
- Consent to biopsy taken prior to starting treatment and Week 8 (± 1 week) of treatment.
- At least 18 years of age.
- Life expectancy of at least 12 weeks.
- Women of childbearing potential must use adequate birth control for the study duration and 6 months afterwards. She must use contraceptive methods with a failure rate of < 1% to prevent pregnancy* and drug exposure of a partner. Male partners must refrain from donating sperm from their partner’s first IMP dose until 6 months after their partner’s last IMP dose. * Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD) or intrauterine hormone-releasing system (IUS); bilateral tubal occlusion, vasectomy, and sexual abstinence.
- Willingness and ability to comply with study procedures, visit schedules, study restrictions and requirements.
- Able to fully understand and participate in study-related procedures, including compliance and patient reported outcome (PRO).
- Written informed consent. Subjects must give informed consent prior to any study-specific procedure.
Exclusion Criteria
- Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers, and cancer types not mentioned in the inclusion criteria.
- Primary platinum-refractory disease, defined as tumor progression during or within 12 weeks from end of first platinum treatment.
- Concurrent cancer therapy (including anti-hormonal therapy for breast cancer unless it is omitted at the latest at study enrollment).
- Received other than platinum-containing therapy for primary disease (first-line treatment).
- Received non-platinum-containing chemotherapy line (e.g. weekly paclitaxel) in treatment of recurrent ovarian cancer. Maintenance with bevacizumab and/or PARP-inhibitor is allowed.
- Treatment with an investigational agent concurrently, or where the last dose was administered within 5 elimination half-lives or where pharmacological activity may still be present as assessed by the Investigator.
- Previous malignant disease: subjects are not eligible for the study if actively being treated for invasive cancer other than ovarian cancer. Subjects with previous malignant disease other than ovarian cancer who are relapse-free and treatment-free for more than three years may enter this study (exception: anti-hormonal therapy, which must be omitted at the latest at study enrollment). Subjects with previous history of in situ carcinoma, stage 1A cervical cancer or non-invasive basal cell and squamous cell skin carcinoma can enter this trial.
- Immunodeficiency or organ transplant. Autoimmune or inflammatory condition that requires immunosuppressive or steroid therapy during the course of the study. Subjects using immunosuppressive medications within 14 days prior to the first IMP dose, except for topical medications (intranasal, inhaled, local injection, systemic [prednisolone equivalent 10 mg/day or less]) or as needed for hypersensitivity reactions such as CT scan premedication.
- Live vaccines within 28 days prior to the first IMP dose.
- Major surgery within 28 days prior to the first IMP dose, or not recovered from previous surgery to CTCAE (v5) grade 1 equivalent.
- Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- Transient ischemic attack (TIA) or stroke, including bleeding, within the past 6 months.
- Brain metastases.
- Major cardiac dysfunction defined as > NYHA II.
- Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug.
- Serious, uncontrolled, and active infection at enrollment, as determined by the Investigator.
- Pregnancy or breastfeeding.
- Persistence of clinically relevant therapy-related toxicity from previous chemotherapy (≥ CTCAE grade 3, except for liver and gastrointestinal ≥ CTCAE grade 2).
- Need for concomitant use of drugs that are: moderate or strong inhibitors of CYP3A4 that may increase concentrations of KAND567; Inducers of CYP3A4 that may decrease concentrations of KAND567; highly dependent on CYP2B6, CYP2C8 or CYP3A4 for their metabolism where KAND567 may increase their concentrations. Treatment with such drugs should have been stopped at least five half-lives before initiation of KAND567 therapy. A list of drugs is provided in Appendix 3.
- Continuous use of herbal preparations (e.g., St. John’s wort) within 2 weeks prior to enrollment.
- Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (e.g., compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- Known or suspected hypersensitivity to any of the IMPs.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Recruiting | 14 Apr 2023 | 10 |
 Norway | Not Recruiting | 14 Apr 2023 | 10 |
 Sweden | Not Recruiting | 14 Apr 2023 | 10 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Carboplatin Accord 10 mg/ml koncentrat till infusionsvätska, lösning | Test | KONCENTRAT TILL INFUSIONSVÄTSKA, LÖSNING | INTRAVENOUS USE | — | — | PRD2005432 |
Carboplatin Actavis 10 mg/ml koncentrat till infusionsvätska, lösning | Test | KONCENTRAT TILL INFUSIONSVÄTSKA, LÖSNING | INTRAVENOUS USE | — | — | PRD925304 |
Carboplatin Accord 10 mg/ml konsentrat til infusjonsvæske, oppløsning | Test | KONSENTRAT TIL INFUSJONSVÆSKE, OPPLØSNING | INTRAVENOUS USE | — | — | PRD415291 |
Carboplatin Ebewe 10 mg/ml koncentrat till infusionsvätska, lösning | Test | KONCENTRAT TILL INFUSIONSVÄTSKA, LÖSNING | INTRAVENOUS USE | — | — | PRD742837 |
Carboplatin ”Accord”, koncentrat til infusionsvæske, opløsning | Test | KONCENTRAT TIL INFUSIONSVÆSKE, OPLØSNING | INTRAVENOUS USE | — | — | PRD2005407 |
Carboplatin Accord 10 mg/ml koncentrat till infusionsvätska, lösning | Test | KONCENTRAT TILL INFUSIONSVÄTSKA, LÖSNING | INTRAVENOUS USE | — | — | PRD2005430 |
Carboplatin ”Accord”, koncentrat til infusionsvæske, opløsning | Test | KONCENTRAT TIL INFUSIONSVÆSKE, OPLØSNING | INTRAVENOUS USE | — | — | PRD2005406 |
Carboplatin Accord 10 mg/ml konsentrat til infusjonsvæske, oppløsning | Test | KONSENTRAT TIL INFUSJONSVÆSKE, OPPLØSNING | INTRAVENOUS USE | — | — | PRD2005420 |
Carboplatin ”Accord”, koncentrat til infusionsvæske, opløsning | Test | KONCENTRAT TIL INFUSIONSVÆSKE, OPLØSNING | INTRAVENOUS USE | — | — | PRD2005405 |
Carboplatin Fresenius Kabi | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | — | — | PRD669099 |