Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

NOX66 800 mg daily (400 mg suppository twice daily \[BID\]).

NOX66

NOX66 1200 mg daily (600 mg suppository BID).

NOX66 1600 mg daily (800 mg suppository BID).

NOX66 2400 mg daily (1200 mg suppository BID).

The dose levels of EBRT will be either 8 Gy as a single fraction, or 20/25 Gy as 5 fractions given over 5 to 10 days.

EBRT

This is a Phase 1b/Phase 2a, open-label, multicenter study to determine the safety, tolerability, recommended Phase 2 dose (RP2D), efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) properties of idronoxil when rectally administered as a suppository (NOX66) to patients with any solid tumor (Part 1) and patients with metastatic castration-resistant prostate cancer (mCRPC), breast cancer (BC) and non-small-cell lung cancer (NSCLC) (Part 2) who are eligible for low-dose external beam radiotherapy (EBRT) for at least one symptomatic or minimally symptomatic lesion (for the prevention of symptoms).

The study is divided into 2 parts: Part 1 (dose escalation) and Part 2 (dose expansion). The study design allows an exploration of different doses of NOX66 (800 mg, 1200 mg, 1600 mg and 2400 mg) with safety monitoring to ensure the safety of the patients. In Cycle 1, NOX66 will be administered for 14 days followed by a 7-day rest period on a 21-day cycle. From Cycle 2 onwards, NOX66 will be administered for 7 days followed by a 7-day rest period on a 14-day cycle. Patients will continue to receive NOX66 on a cyclical basis until disease progression, unacceptable toxicity, withdrawal of consent, start of a new anticancer therapy, withdrawal of the patient by the Investigator or the end of study is reached.

A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

A Phase 1b/2a Multicenter Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors

Determination of the maximum tolerated dose (MTD) and RP2D of NOX66 in combination with low-dose EBRT in patients with any solid tumor. 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.

Evaluation of the effect of NOX66 on PSA response in patients with mCRPC. 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.

Characterization of the safety and tolerability of NOX66.

Evaluation of the safety and tolerability of both doses of EBRT (8 Gy or 20/25 Gy).

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC.

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC and other solid tumors. The ORR, defined as the percentage of patients with CR and PR, will be assessed based on change from baseline imaging (Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1 \[all tumor types\] and Prostate Cancer Working Group 3 \[PCWG3\] criteria \[mCRPC\] for measurable or evaluable lesions).

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC and other solid tumors. Duration of response is defined as the time from the first documented overall response of CR, PR or SD to the first documented overall response of progressive disease.

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC and other solid tumors. ECOG is a 6-point scale where 0= Fully active, 1= Restricted in physically strenuous activity, 2=Up and about more than 50% of waking hours, 3= Capable of only limited selfcare, confined to a bed or chair more than 50% of waking hours, 4= Completely disabled, and 5=Dead. Higher scores mean a worse outcome.

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC and other solid tumors.

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC. Progression-free survival is defined as the duration of time from first dose administration to date of disease progression is objectively documented, including tumor progression, early discontinuation or death prior to data cut off.

Evaluation of the preliminary clinical efficacy of NOX66 plus low-dose EBRT in patients with mCRPC. Overall survival is defined as time from the date of first dose administration to date of death due to any cause.

The effects of NOX66 on pain and other cancer-related signs and symptoms will be explored. Worst pain, general pain and pain's interference with daily life will be assessed during the study drug using the BPI-SF. The BPI-SF comprises a total of 15 items measuring 2 domains: pain severity and pain interference. Items measuring pain severity (including 'worst pain') are rated on an 11 point numeric rating scale ranging from 0=No pain to 10=Pain as bad as you can imagine. Higher scores mean a worse outcome.

The effects of NOX66 on pain and other cancer-related signs and symptoms will be explored. Skeletal-related events and SSEs will be evaluated based on the patient's clinical history and examinations, including but not limited to incidence of fractures and pain.

The effects of NOX66 on pain and other cancer-related signs and symptoms will be explored. The dose of morphine administration and analgesic use will be assessed based on the patient's concomitant medication use assessment.

The effects of NOX66 on pain and other cancer-related signs and symptoms will be explored. The frequency of morphine administration and analgesic use will be assessed based on the patient's concomitant medication use assessment.

The Sponsor has developed a questionnaire to evaluate the patient's experience with the suppository dosage form. This will consist of a set of 10 questions, with some questions requiring simple yes or no answers, and other questions are to be rated on a scale of 10 (range 1 to 10) where higher scores mean a worse outcome.

The questionnaire assesses important functioning domains (e.g., physical, emotional, social) and common cancer symptoms (e.g., fatigue, pain, nausea, vomiting, appetite loss). The instrument is composed of 30 items. All symptom scales range from 1-4 with higher values representing higher levels of symptoms, except for the items that evaluate overall quality of life which are rated on a 7-point scale (range 1-7) where higher score represent a better quality of life.

The FACT-P questionnaire is a relevant, worldwide tool used for assessing the health-related QoL in men with prostate cancer. The FACT-P is a 39-item questionnaire composed of the FACT-General (FACT-G) original subscales (Physical Well-being, Social/Family Well-being, Emotional Well-being and Functional Well-being) and a Prostate Cancer Subscale. Each item is rated on a 5-point scale ranging from 0 (not at all) to 4 (very much). A higher score indicates a better QoL.

Noxopharm Limited

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.

NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion.

Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.

Irradiation Therapy

Marinella Messina, PhD

The study is intended as a Proof of Concept and dose confirmation study. The primary objective of this study is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress to Phase 2/3.

This study will investigate three escalating doses of NOX66 in combination with palliative dose of radiation therapy to establish safety profile and / or obtain efficacy signals and to determine the optimal dose for future radiation therapy combination studies.

The key hypotheses to be tested in this study are:

1. That NOX66 can be safely added to palliative dose radiation therapy.
2. That NOX66 may sensitise tumours to palliative doses of radiation therapy
3. That NOX66 in combination with radiation therapy may trigger or augment an abscopal effect

Participants will have a minimum of 1 symptomatic lesion amenable to radiation therapy.

Radiation therapy will be delivered at a 20Gy dosage over 5 fractions. NOX66 will be taken on 13 consecutive days starting 1 day prior to radiotherapy.

The response of irradiated and non-irradiated target tumour lesions will be measured by CT/MRI scan and RECIST1.1 criteria at three time points post treatment. Pain response will be evaluated using the Brief Pain Inventory-Short Form (BPI-SF) instrument at five time points post treatment.

Patients will be suitable for the study as they become indicated for palliative radiation therapy for management of their cancer.

This study will enrol up to 24 patients in 3 NOX66 dose level cohorts of 4 patients (n=12) and an expansion cohort of 12 patients. Dose escalation decisions will be based on patients who experience adverse events directly related to NOX66 treatment.

Following the review of accumulated safety data, disease status and treatment efficacy signals at WEEK 6 for the first 12 patients, the Study Steering Committee will determine the dose at which to continue treatment for the expansion patient Cohort 4 in the study. A further 12 patients will be recruited at this dose level.

Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer

NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study

De-identified individual participant data for primary and secondary outcome measure will be made available within 12 months after study completion.

Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events of at least CTCAE Version 4.03 Grade 2 in severity. Treatment emergent AEs are those with an onset on or after the initiation of therapy. Timepoints for AE /SAE assessment are Day 2 (start of radiation therapy treatment and one day after start of NOX66 treatment), Day 6, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

Other safety endpoints include laboratory results which are assessed at Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

Further safety endpoints include laboratory results and ECG findings which are assessed Screening, End of treatment (Day 16-17) and from enrolment up to week 6, week 12, week 24.

RECIST response in target irradiated and non-irradiated lesions based on radiographic CT/MRI scan. RECIST 1.1 criteria are Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)

RECIST 1.1 assessment of response in Non-target lesions

Overall RECIST 1.1 response based on combined assessment criteria for target, non-target and new lesions lesions as Complete Response (CR), Partial Response (PR), Stable Disease(SD) and Progressive Disease (PD)

Change from baseline in pain score based on responses to BPI-SF

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

NOX66 800 mg (400 mg suppository twice daily \[BID\]).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

NOX66 1200 mg daily (600 mg suppository BID).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

NOX66 1800 mg daily (600 mg suppository thrice daily).

Monotherapy: 7 days of NOX66 followed by 5 days washout. Combination therapy: 7 days of NOX66 followed by 14 days washout in a 21-day cycle, for up to 6 cycles.

MTD of the combination of NOX66 and doxorubicin will be determined in the dose-escalation cohort of the study. The selected dose will be administered in combination with Doxorubicin.

Doxorubicin will be given at 75 mg/m\^2 as an intravenous infusion on Day 2 of the 21-day cycle for up to 6 cycles.

This is a Phase I, open-label, dose-escalation and dose-expansion study of NOX66 given rectally, in cohorts of patients with metastatic soft tissue sarcoma (STS) who have not been exposed to anthracycline therapy, using a fixed dose-escalation schema every 21 days to establish the maximum tolerated dose (MTD) of the combination of NOX66 and doxorubicin.

The study will contain dose-escalation cohorts and dose-expansion cohorts. The study design allows an exploration of different doses of NOX66 with safety monitoring to ensure the safety of the patients.

Dose-escalation cohorts: It will include three planned Treatment Groups (800, 1200, 1800 mg daily) and patients enrolled in these groups will receive 7 days of monotherapy treatment with NOX66 followed by a 5-day washout period. Thereafter, patients will enter a combination therapy (only if no significant toxicity is observed during monotherapy). This will commence with Cycle 1, which will consist of 7 days of NOX66, and on Day 2 of the 21-day cycle, doxorubicin will be administered. Patients will continue to be treated for up to 6 x 21-day cycles of NOX66 and doxorubicin. New patients will be entered at the next dose level of NOX66, if no dose-limiting toxicities have occurred among the first 3 patients at the end of cycle 1. During the dose-escalation, MTD of the combination of NOX66 and doxorubicin will be determined.

Dose-expansion cohort: On completion of the dose-escalation cohort, patients will be enrolled into a dose-expansion at the MTD of the combination of NOX66 and doxorubicin. All patients will enter directly into 21-day combination cycles and will be given NOX66 therapy for 7 days and doxorubicin will be administered on Day 2 of each cycle. Treatment will be terminated upon disease progression, unacceptable toxicity, or a maximum of 6 cycles.

A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma

A Dose Escalation and Dose Expansion Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma - CEP-2

Determination of the MTD of NOX66 in combination with doxorubicin. 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.

The number of patients with BNP levels greater than 500 pg/mL and with BNP levels between 100 and 500 pg/mL from baseline will be presented.

Number of patients with change in troponin levels from baseline will be evaluated to characterize safety and tolerability of NOX66.

Determination of single-and multiple-dose pharmacokinetics (PK) of idronoxil

Determination of single-and multiple-dose PK of idronoxil

Determination of single-and multiple-dose PK of idronoxil. Terminal elimination rate constant will be calculated from a semi-log plot of the blood concentration versus time (kel\^a)

Determination of single-and multiple-dose PK of idronoxil and doxorubicin

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. DCR is defined as the percentage of patients with a best overall response of complete response (CR), partial response (PR) or stable disease, and will be assessed based on change from baseline imaging by (Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. The ORR, defined as the percentage of patients with CR and PR, and will be assessed based on change from baseline imaging by (RECIST) v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. CR will be assessed based on change from baseline imaging (RECIST) v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. PR will be assessed based on change from baseline imaging (RECIST) v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. SD will be assessed based on change from baseline imaging (RECIST) v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. PFS is defined as the time in months from initial treatment until death, disease progression, or censoring.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. PD will be assessed based on change from baseline imaging (RECIST) v1.1.

Evaluation of preliminary efficacy of NOX66 in combination with doxorubicin. OS is defined as the time in months from initial treatment until death or censoring.

Determination of quality of life (QOL) of NOX66 in combination with doxorubicin. The questionnaire assesses important functioning domains (e.g., physical, emotional, social) and common cancer symptoms (e.g., fatigue, pain, nausea, vomiting, appetite loss). The instrument is composed of 30 items. All symptom scales range from 1-4 with higher values representing higher levels of symptoms, except for the items that evaluate the overall quality of life which are rated on a 7-point scale (range 1-7) where higher scores represent a better quality of life.

Determination of quality of life (QOL) of NOX66 in combination with doxorubicin. Fatigue will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - EORTC QLQ-FA12. The QLQ-FA12 incorporates three multi-item scales to assess physical fatigue, emotional fatigue, and cognitive fatigue. In addition, two single items assess interference with daily life and social sequelae. All of the scales and single-item measures range in score from 0 to 100. For all the scales and single items, a high score represents a high level of symptomatology or problems.

Determination of quality of life (QOL) of NOX66 in combination with doxorubicin. The effects of NOX66 on pain and other cancer-related signs and symptoms will be explored. Worst pain, general pain and pain's interference with daily life will be assessed during the study drug using the BPI-SF. The BPI-SF comprises a total of 15 items measuring 2 domains: pain severity and pain interference. Items measuring pain severity (including 'worst pain') are rated on an 11 point numeric rating scale ranging from 0=No pain to 10=Pain as bad as you can imagine. Higher scores mean a worse outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors	NCT04957290	Metastatic Cast...	NOX66 NOX66 NOX66 NOX66 NOX66 EBRT	18 Years -	Noxopharm Limited
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer	NCT03307629	Cancer	NOX66 Irradiation The...	18 Years -	Noxopharm Limited
A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma	NCT05100628	Metastatic Soft...	NOX66 NOX66 NOX66 NOX66 Doxorubicin	18 Years -	Noxopharm Limited
A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors	NCT04957290	Metastatic Cast...	NOX66 NOX66 NOX66 NOX66 NOX66 EBRT	18 Years -	Noxopharm Limited
Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer	NCT03307629	Cancer	NOX66 Irradiation The...	18 Years -	Noxopharm Limited

Spots Global Cancer Trial Database for nox66

Every month we try and update this database with for nox66 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nox66

Every month we try and update this database with for nox66 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nox66 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.