Safety, PK and Efficacy of NOX66 as a Monotherapy and Combined With Carboplatin in Refractory Solid Tumours

NCT02941523 | Completed Phase 1 Results

• 1 other identifier: NOX66-001A
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From enrollment through 30 days after the last cycle of therapy (8 months)

Secondary Outcomes (2)

• Objective Response Rate (ORR) at Cycle 3 and at Cycle 6 of Combination Therapy

  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

  Radiological evaluation at baseline and at 3 months and at 6 months

Study Arms (3)

1a NOX66

EXPERIMENTAL

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

1b NOX66 and Carboplatin (combined)

EXPERIMENTAL

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

2a NOX66 and Carboplatin

EXPERIMENTAL

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

Interventions

NOX66 DRUG

NOX66 administration

Also known as: Idronoxil

1a NOX66; 1b NOX66 and Carboplatin (combined); 2a NOX66 and Carboplatin

Carboplatin DRUG

Carboplatin administration

Also known as: Paraplatin

1b NOX66 and Carboplatin (combined); 2a NOX66 and Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent
• Male or female ≥18 years of age
• Histologic or cytologic confirmed locally advanced or metastatic cancer that has no standard therapeutic alternatives.
• ECOG Performance status 0-1
• A minimum life expectancy of 12 weeks
• Adequate bone marrow, hepatic and renal function as evidenced by:
• Absolute neutrophil count (ANC) \> 1.5 x 109/L
• Platelet count \> 100 x 109/L
• Hemoglobin \> 9.0 g/dL
• Serum bilirubin \< 1.5 x ULN
• AST/ALT (SGOT/SGPT) 2.5 x ULN for the reference laboratory or \< 5 x ULN in the presence of liver metastases
• Serum creatinine 1.5 x ULN
• Female patients who are known to be capable of conception should have a negative serum pregnancy test (beta-human chorionic gonadotropin (β-hCG)) within 1 week of starting the study
• All potentially fertile patients will agree to use an effective form of contraception during the study and for 90 days following the last dose of NOX66 (an effective form of contraception is defined as an oral contraceptive or a double barrier method
• At least 4 weeks must have elapsed prior to commencement of NOX66 treatment since prior chemotherapy, investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE Grade 1

You may not qualify if:

• Patients who are pregnant or breastfeeding.
• Uncontrolled infection or systemic disease.
• Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease, angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months.
• Patients with QTc of \> 470 msec on screening ECG. (If a patient has QTc interval \>470 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the 3 screening ECGs must be \<470 msec in order for the patient to be eligible for the study.
• Any major surgery, radiotherapy, or immunotherapy within the last 21 days (limited palliative radiation is allowed \> 2 weeks).
• Chemotherapy regimens with delayed toxicity within the last 4 weeks. Chemotherapy regimens given continuously or on a weekly basis with limited potential or delayed toxicity within the last 2 weeks.
• No concurrent systemic chemotherapy or biologic therapy is allowed.
• Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both).
• History of solid organ transplantation.
• Psychiatric disorder or social or geographic situation that would preclude study participation.
• Known unsuitability for treatment with carboplatin including renal disease where there is impaired glomerular filtration rate (GFR).

Sponsors & Collaborators

• Noxopharm Limited: lead

Study Sites (4)

Academician Z.Tskhakaia West Georgia National Center of Interventional Medicine" LTD/ Oncology Unit- JSC "EVEX Medical Corporation" group member

Kutaisi, 4600, Georgia

Location

Tbilisi State Medical University's First University Clinic, Department Of Oncology

Tbilisi, 0141, Georgia

Location

LTD, Medulla Chemotherapy and Immunotherapy Clinic

Tbilisi, 0186, Georgia

Location

JSC, Neo Medi

Tbilisi, 0313, Georgia

Location

MeSH Terms

Conditions

Neoplasms

Interventions

phenoxodiol; Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Limitations and Caveats

Due to Phase 1 nature of the study, the subject sample size was small.

Results Point of Contact

• Title: Clinical Manager
• Organization: Noxopharm Limited

marinella.messina@noxopharm.com

+61 499005049

Study Officials

• Graham Kelly

  Noxopharm Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 21, 2016
• Study Start: March 3, 2017
• Primary Completion: December 31, 2018
• Study Completion: January 10, 2019
• Last Updated: June 2, 2021
• Results First Posted: June 2, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 12-18 months after study completion

Locations

GE (4)