A Phase 1/2 interventional study of NOX66 and Carboplatin in Cancer, sponsored by Noxopharm Limited. Completed at 4 sites in Georgia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-02.
Sponsored by Noxopharm Limited · Phase 1/2, Interventional, and Treatment
The study evaluates the safety and activity of NOX66 in patients with refractory solid tumors that are non responsive to standard therapies.
This is a two part with a potential third part, open-label, multicenter, dose escalation study of NOX66 as monotherapy and in combination with carboplatin.
Idronoxil is a synthetic small molecule that pre-clinical studies have identified as a strong candidate for development as a chemo-sensitising drug.
Human studies using idronoxil administered in oral and intravenous dosage forms have shown that the drug is highly susceptible to Phase 2 metabolism, resulting in loss of bio-activity.
NOX66 is idronoxil in a new dosage formulation developed specifically to protect the drug from Phase 2 metabolism and thereby ensure retention of the majority of administered drug in a bio-active form.
The main purpose of the current study is to confirm the safety of the new dosage formula both as a monotherapy and in combination with carboplatin, given that it is anticipated that the drug will be present in the body in a bio-active form at considerably higher levels than previously achieved.
A secondary objective is to observe if NOX66 is able to restore response to carboplatin in tumours considered unresponsive to this chemotherapy, and moreover to provide a meaningful clinical benefit in combination with a lower-than-normal dosage of carboplatin.
Patients will be drawn from 5 cancer types: prostate cancer, lung cancer, breast cancer, ovarian cancer, head and neck cancer.
The study will commence with a Phase 1a (Run-in) arm comparing the relative tolerability and safety of two different dosages of idronoxil/NOX66 as a 14-day monotherapy course.
Providing there is no dose limiting toxicity (DLT), patients then progress onto the Phase 1b (Combination) arm of the study, remaining on the same dosage. In this arm, patients receive 6 treatment cycles, each of 28 days comprising NOX66 (idronoxil) treatment on Days 1-7 and carboplatin on Day 2 of each treatment cycle.
Any meaningful clinical responses occurring in the Phase 1b (Combination) Arm will trigger a Phase IIa (Combination) Arm where an additional 10 patients will be recruited into a maximum of 2 cohorts of the same tumour type (prostate, lung, breast, ovarian, or head and neck). These patients will receive the same combination dosage providing the observed clinical responses and treated with that dosage for a maximum of 6 treatment cycles.
Noxopharm Limited is the lead sponsor of 7 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adequate bone marrow, hepatic and renal function as evidenced by:
Exclusion Criteria:
NOX66 administered daily for 14 day in a 21-day treatment cycle. NOX66 treatment given to two cohorts of patients as 1 of 2 dose regimens: Regimen 1: 400 mg; Regimen 2: 800 mg (idronoxil)
Drug: NOX66
NOX66 administered on Days 1-7 and carboplatin IV infusion on Day 2 of each 28-day treatment cycle up to 6 cycles. NOX66 at the same dosage received in the Run-In Arm combined with 2 carboplatin doses starting with low dose carboplatin AUC = 4 for treatment cycles 1-3 followed by higher dose carboplatin AUC = 6 for treatment cycles 4-6.
Drug: NOX66 · Drug: Carboplatin
This arm triggered by observed meaningful clinical responses from the 1b Combination Arm in particular disease indications. Treatment NOX66 + carboplatin administered over 6 cycles each of 28-days at observed clinical response dosage. A maximum of 2 cohorts, each comprising patients with specific tumour type.
Drug: NOX66 · Drug: Carboplatin
NOX66 administration
Also known as: Idronoxil
Carboplatin administration
Also known as: Paraplatin
Number of Participants Who Experience Dose Limiting Toxicity (DLT) During NOX66 Monotherapy and During NOX66 Combination With Carboplatin
Dose limiting toxicity during monotherapy and combination therapy defined as any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE version 4.03\]) (related to therapy) excluding Grade 3 or more neutropenia lasting greater than 5 days or thrombocytopenia associate with bleeding or Grade 4 thrombocytopenia.
Time frame: Up to 1 month for NOX66 monotherapy from enrollment and up to 7 months from start of NOX66 combination therapy
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (SAEs) Related to NOX66.
An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related are events which had causal relationship to study drug as assessed by the Investigator and were suspected to be reasonably related to the study drug.
Time frame: From enrollment through 30 days after the last cycle of therapy (8 months)
Objective Response Rate (ORR) at Cycle 3 and at Cycle 6 of Combination Therapy
Objective response rate defined as the percentage of participants achieving a complete response (CR) and or partial response (PR) after treatment with NOX66 and carboplatin therapy as assessed by Response Evaluation Criteria in solid tumors (RECIST) v1.1. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and no new lesions.
Time frame: Radiological evaluation at baseline and at 3 months and at 6 months
Overall Clinical Response Rate at Cycle 3 and at Cycle 6 of Combination Therapy
Overall Clinical response rate defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1 after combination of NOX66 and carboplatin therapy. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Time frame: Radiological evaluation at baseline and at 3 months and at 6 months
| Milestone | NOX66 400 mg | NOX66 800 mg |
|---|---|---|
| Started | 8 | 8 |
| Completed | 8 | 7 |
| Not completed | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | NOX66 400 mg | NOX66 800 mg |
|---|---|---|
| Started | 8 | 10 |
| Completed | 3 | 6 |
| Not completed | 5 | 4 |
| Withdrew: Adverse event | 0 | 1 |
| Withdrew: Death | 1 | 2 |
| Withdrew: Disease progression | 2 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 |
Dose limiting toxicity during monotherapy and combination therapy defined as any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE version 4.03\]) (related to therapy) excluding Grade 3 or more neutropenia lasting greater than 5 days or thrombocytopenia associate with bleeding or Grade 4 thrombocytopenia.
| Participants | NOX66 400 mg Monotherapy | NOX66 400 mg Combination Therapy | NOX66 800 mg Monotherapy | NOX66 800 mg Combination Therapy |
|---|---|---|---|---|
| Number of Participants Who Experience Dose Limiting Toxicity (DLT) During NOX66 Monotherapy and During NOX66 Combination With Carboplatin | 0 | 0 | 0 | 0 |
An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Treatment-related are events which had causal relationship to study drug as assessed by the Investigator and were suspected to be reasonably related to the study drug.
| Participants | NOX66 400 mg Monotherapy | NOX66 400 mg Combination Therapy | NOX66 800 mg Monotherapy | NOX66 800 mg Combination Therapy |
|---|---|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (SAEs) Related to NOX66. | 0 | 0 | 1 | 0 |
Objective response rate defined as the percentage of participants achieving a complete response (CR) and or partial response (PR) after treatment with NOX66 and carboplatin therapy as assessed by Response Evaluation Criteria in solid tumors (RECIST) v1.1. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and no new lesions.
| Participants | NOX66 400 mg + Carboplatin (AUC4) to Cycle 3 | NOX66 400 mg + Carboplatin (AUC6) to Cycle 6 | NOX66 800 mg + Carboplatin (AUC4) to Cycle 3 | NOX66 800 mg + Carboplatin (AUC6) to Cycle 6 |
|---|---|---|---|---|
| Complete Response | 0 | 0 | 0 | 0 |
| Partial Response | 0 | 0 | 0 | 1 |
Overall Clinical response rate defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1 after combination of NOX66 and carboplatin therapy. CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to \<10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
| Participants | NOX66 400 mg + Carboplatin (AUC4) to Cycle 3 | NOX66 400 mg + Carboplatin (AUC6) to Cycle 6 | NOX66 800 mg + Carboplatin (AUC4) to Cycle 3 | NOX66 800 mg + Carboplatin (AUC6) to Cycle 6 |
|---|---|---|---|---|
| Overall Clinical Response Rate at Cycle 3 and at Cycle 6 of Combination Therapy | 4 | 1 | 7 | 5 |
Collected over 7 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Monotherapy Phase, NOX66 400 mg | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) |
| Monotherapy Phase, NOX66 800 mg | 0/7 (0%) | 0/7 (0%) | 1/7 (14.3%) |
| Combination Phase, NOX66 400 mg | 1/8 (12.5%) | 1/8 (12.5%) | 6/8 (75%) |
| Combination Phase, NOX66 800 mg | 2/10 (20%) | 3/10 (30%) | 5/10 (50%) |
| Event | Monotherapy Phase, NOX66 400 mg | Monotherapy Phase, NOX66 800 mg | Combination Phase, NOX66 400 mg | Combination Phase, NOX66 800 mg |
|---|---|---|---|---|
| sudden deathGeneral disorders | 0/8 | 0/3 | 1/8 | 0/10 |
| Infusion reactionInjury, poisoning and procedural complications | 0/8 | 0/7 | 0/8 | 1/10 |
| ComaNervous system disorders | 0/8 | 0/7 | 0/8 | 1/10 |
| haemorrhageGastrointestinal disorders | 0/8 | 0/7 | 0/8 | 1/10 |
| Event | Monotherapy Phase, NOX66 400 mg | Monotherapy Phase, NOX66 800 mg | Combination Phase, NOX66 400 mg | Combination Phase, NOX66 800 mg |
|---|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/8 | 1/7 | 1/8 | 3/10 |
| NeutropeniaBlood and lymphatic system disorders | 0/8 | 0/7 | 1/8 | 2/10 |
| HypocalcaemiaMetabolism and nutrition disorders | 0/8 | 0/7 | 1/8 | 2/10 |
| Iron deficiency anaemiaBlood and lymphatic system disorders | 0/8 | 0/7 | 1/8 | 1/10 |
| PericarditisCardiac disorders | 1/8 | 0/7 | 0/8 | 0/10 |
| Abdominal pain, upperGastrointestinal disorders | 0/8 | 0/7 | 1/8 | 0/10 |
| DiarrhoeaGastrointestinal disorders | 0/8 | 0/7 | 1/8 | 0/10 |
| FlatulenceGastrointestinal disorders | 0/8 | 0/7 | 1/8 | 0/10 |
| NauseaGastrointestinal disorders | 0/8 | 0/7 | 1/8 | 0/10 |
| AstheniaGeneral disorders | 0/8 | 0/7 | 1/8 | 0/10 |
Enrolled population = 19 Safety population includes those that received at least 1 NOX66 dose = 18 (n=8 in 400 mg arm; n=10 in 800 mg arm) Efficacy population = 14 (n=5 in 400 mg arm; n=9 in 800 mg arm)
| Age, Categorical(Participants) | NOX66 400 mg | NOX66 800 mg | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 8 | 14 |
| >=65 years | 2 | 3 | 5 |
| Sex: Female, Male(Participants) | NOX66 400 mg | NOX66 800 mg | Total |
|---|---|---|---|
| Female | 5 | 7 | 12 |
| Male | 3 | 4 | 7 |
| Ethnicity (NIH/OMB)(Participants) | NOX66 400 mg | NOX66 800 mg | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 8 | 11 | 19 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | NOX66 400 mg | NOX66 800 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 8 | 11 | 19 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | NOX66 400 mg | NOX66 800 mg | Total |
|---|---|---|---|
| Georgia | 8 | 11 | 19 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — De-identified individual participant data for primary and secondary outcome measure will be made available within 12 months after study completion
Supporting information: Study protocol, Csr
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
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