E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors
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E.1.1.1 | Medical condition in easily understood language |
Prostate Cancer and Other Solid Tumors
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1 (Dose Escalation): To determine the MTD(Maximum Tolerated Dose) and RP2D(Recommended Phase 2 Dose) of NOX66 in combination with low-dose EBRT(External Beam Radiotherapy) in patients with any solid tumor Part 2 (Dose Expansion): -Arm 1: To evaluate the effect of NOX66 on PSA(Prostate-Specific Antigen) response in patients with mCRPC (metastatic Castration-Resistant Prostate Cancer). -Arm 2: To evaluate the effect of NOX66 on DCR(Disease Control Rate) in patients with BC(Breast Cancer) and NSCLC(Non-Small-Cell Lung Cancer) |
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E.2.2 | Secondary objectives of the trial |
To characterize the safety and tolerability of NOX66/ To evaluate the safety and tolerability of both doses of EBRT(External Beam Radiotherapy)/ To evaluate the exposure of idronoxil/ To evaluate the preliminary clinical efficacy of NOX66 plus low-dose EBRT(External Beam Radiotherapy) in patients with mCRPC(metastatic Castration-Resistant Prostate Cancer) and other solid tumors/ To Explore the effects of NOX66 on pain and other cancer-related signs and symptoms/ To evaluate the QoL(Quality of Life) using PRO(Patient Reported Outcome) questionnaires
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patient has a minimum life expectancy of 6 months. -Patient is 18 years or older at the time of signing the informed consent. -Histological or cytological confirmation of prostate cancer, BC, NSCLC and any other solid tumors. -Confirmed metastatic disease by imaging (e.g., bone scans, X-rays, ultrasound, computerized tomography [CT], magnetic resonance imaging [MRI]). -Documented disease progression (e.g., based on radiographic imaging, PSA or other clinical parameters) following first or later lines of anticancer systemic treatment. -Patient is eligible for low-dose EBRT for at least one lesion. -Patients with prior RT are eligible, only if there is no potential for field overlap between the prior RT and the planned RT. -For patients with BC or NSCLC: Patient must have at least one measurable lesion as per RECIST v1.1 (in Part 2 only). -Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. -Adequate bone marrow function defined as: • Absolute neutrophil count ≥ 1.5 × 109/L. • Platelet count ≥ 100 × 109/L. • Hemoglobin ≥ 9.0 g/dL (with or without transfusion). -Adequate renal function defined as: • Creatinine clearance as measured by the Cockcroft-Gault equation > 30 mL/min. -Adequate liver function defined as: • Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN; patients with confirmed Gilbert’s syndrome may be included in the study). • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastasis). Elevated alkaline phosphatase is not exclusionary if due to the presence of bone metastasis and liver function is otherwise considered adequate in the Investigator’s judgement. -Baseline testosterone levels ≤ 14.4 ng/dL and ongoing medical castration must be maintained throughout the duration of the study. -Patient has evidence of symptomatic and/or progressive disease. Progressive disease is defined as any one of the following: • Radiographic disease progression in soft tissue (nodule or visceral metastasis) and/or bone with or without PSA progression. Objective evidence of increase in radiographic lesions or the appearance of 2 or more new lesions. • Prostate-specific antigen progression: At least 3 consecutive rising PSA levels (≥ 2 to 5 ng/mL) separated by at least 1 week, with castrate levels of testosterone. -Known hormone receptor status (estrogen receptors/progesterone receptors or estrogen receptors alone). Breast cancer patients are allowed to be on background hormonal treatment. -Patient must have had a vasectomy or must agree to use a highly effective contraception as detailed in Section 10.5 of this protocol during the treatment period and for at least 3 months after the last dose of study drug and refrain from donating sperm during this period. -A female patient is eligible to participate if she is not pregnant (see Section 10.5), not breastfeeding, and at least one of the following conditions applies: • Not a woman of childbearing potential (WOCBP) as defined in Section 10.5. OR • A WOCBP who agrees to follow the contraceptive guidance in Section 10.5 and not to donate ova during the treatment period and for at least 3 months after the last dose of study drug.
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E.4 | Principal exclusion criteria |
-Patient has tumor involvement of the central nervous system. -Impaired cardiac functioning or clinically significant cardiac disease, including the following: • Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to starting study drug. • Corrected QT interval using Fridericia’s formula > 470 msec on screening ECG. • Uncontrolled clinically significant cardiac arrhythmia. -Uncontrolled hypertension despite two concomitant antihypertensive therapies, defined as supine systolic blood pressure ≥ 150 mmHg or diastolic blood pressure > 100 mmHg based on a mean of three measurements at approximately 2-minute intervals. -Patients who have had a colectomy (total or left hemicolectomy) with re-anastomosis. -Patients for whom administration of the suppositories are likely to cause pain or difficulties in absorption. -Patients with fecal impaction or uncontrolled irritable bowel disease. -Patients with inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis) will be excluded, even if the condition is well controlled. -Active or chronic infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C. Screening of patients with serology testing for these viruses is not required. However, patients who have a past history of viral hepatitis or in whom there is a current suspicion of viral hepatitis will have serology testing for hepatitis B and hepatitis C performed to determine whether there is any current evidence of ongoing infection with these viruses. Patients considered to be at risk for HIV infection should have HIV testing performed. If the test result is negative, the patient will be allowed to participate in the study. -Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the Investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. -Patients with oligometastatic disease (fewer than 5 metastatic lesions) amenable to standard therapy will be excluded. -Major surgery within 4 weeks or minor surgery or biopsy within 1 week of the first dose administration. -Patients who have had RT to the region of the rectum or will require RT to the region of the rectum during the trial. -Uncontrolled active infection requiring intravenous antibiotic, antiviral or anti-fungal medications within 14 days before the first dose administration. Infections (e.g., urinary tract infection) controlled on concurrent anti-microbial agents and anti-microbial prophylaxis per institutional guidelines are acceptable. -Receiving or having received anticancer treatment within the following period prior to the first dose administration: • Cytotoxic treatment: 3 weeks. • Non-cytotoxic drugs, including small molecule investigational products: 3 weeks or 5 terminal half-lives from plasma (whichever is the longest). • Biological products including investigational immune-oncology agents: 4 weeks. • Radiation with a limited field for palliation: 4 weeks. • Radiation to > 30% of the bone marrow: 4 weeks. • Lung radiation: 60 days. -Patient has received corticosteroids at a dose of > 10 mg prednisone/day or equivalent for any reason within 4 weeks prior to receiving the first dose administration. -History of hypersensitivity to active or inactive excipients of study drug or drugs with a similar chemical structure or class to the study drug. -Patient is not willing to use suppositories. -Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. -Patient has a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 prior to Screening or enrollment, or has clinical signs and symptoms consistent with SARS-CoV-2 infection; e.g., fever, dry cough, dyspnea, sore throat, fatigue or positive SARS-CoV-2 test result within 2 weeks prior to Screening. Patients who had symptomatic COVID-19 disease less than 1 month prior to Screening will be excluded. If a patient has had a severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated) within 4 weeks of Screening, or have any sequelae of infection or ongoing infection, the patient will also be excluded. If the patient has had recent (within previous 14 days) exposure to someone who has COVID-19 symptoms, been in contact with someone who has tested positive for COVID-19 or visited a COVID-19 treatment facility, the patient may be re-evaluated for participation in the study after undergoing an isolation period of at least 10 days and having a negative SARS-CoV-2 RT-PCR test prior to enrollment.
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E.5 End points |
E.5.1 | Primary end point(s) |
-Part 1 (Dose Escalation): The primary objective for Part 1 will be determined based on the count of DLTs. • MTD is defined as the dose level at which no more than 1 patient out of 6 experiences a DLT at the end of Cycle 1. • RP2D is the highest dose administered at which no more than 1 patient out of 6 experiences a DLT at the end of Cycle 1 and the dosage form, including the dosing frequency, is acceptable to patients. -Part 2 (Dose Expansion): • PSA response is defined as the proportion of patients with a reduction in PSA in plasma (ng/mL) of ≥ 30% from baseline at the end of Cycles 3 and 6. • DCR is measured by the percentage of patients with a best overall confirmed response of CR or PR and SD. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout trial treatment/follow-up period
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E.5.2 | Secondary end point(s) |
-Safety and tolerability of NOX66 as determined by AEs, TEAEs, clinical laboratory evaluations, vital signs, 12-lead ECG and physical examinations. -Safety and tolerability of both doses of EBRT as determined by AEs, TEAEs, clinical laboratory evaluations, vital signs, 12-lead ECG and physical examinations. -Concentration of idronoxil and selected metabolites in plasma and derived PK parameters, including but not limited to: Cmax, Tmax, AUC(0-t), AUC(0-6), AUC(0-12), AUC(0-inf), Cmin and t½, as data permit. -Preliminary clinical efficacy as determined by: • Change from baseline in PSA (mCRPC only) at any time point. • Overall response rate assessed by RECIST v1.1 criteria (all tumor types) and PCWG-3 criteria (mCRPC). • Duration of response (for patients with measurable disease). • Change from baseline ECOG scores. • Change from baseline in tumor size and number. • PFS and OS. -Effects on pain and other cancer-related signs and symptoms as determined by: • Change from baseline in pain scores based on the BPI-SF questionnaire. • SREs and SSEs. • Change of dose and frequency of morphine administration and analgesic use. -QoL as assessed by: • Change from baseline in PEQ. • Change from baseline in EORTC-QLQ-C30. • Change from baseline in FACT-P (mCRPC only). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout trial treatment/follow-up period
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety, tolerability, RP2D, efficacy, pharmacokinetics and pharmacodynamic of NOX66 |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
United States |
France |
Hungary |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS For the entire study, study completion is defined as the last visit of the last patient for any protocol related activity (last patient, last visit), including telephone contact. For individual patients, study completion is defined as the time of the patient’s last data collection.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |