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Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S

Primary Purpose

Astrocytoma, Brain Cancer, Brain Metastases

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
QBS10072S
Sponsored by
Quadriga Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Astrocytoma focused on measuring Phase 1, Dose escalation, Metastatic, Brain metastasis, Brain metastases, GBM, Astrocytoma, Brain tumor, Cancer, Oncology, Glioblastoma, Glioblastoma multiforme, Brain, Neurology, Neuroscience, Headaches, Vomiting, Seizures, Drowsiness, Chemotherapy, Surgery, Radiation, Neuro-oncology, Blurred vision, Loss of appetite, Speech difficulty, Changes in ability to think and learn, Changes in mood and personality, Persistent headaches, Neuropathologist, Magnetic resonance spectroscopy (MRS), Positron emission tomography (PET scan), Intraoperative MRI, Tumor removal, Craniotomy, Standard external beam radiation therapy, Radiosurgery, Temozolomide, Bevacizumab, Avastin, Neurological exam, TMZ

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female participants aged ≥18 years at the time of informed consent.
  2. Adequate Bone Marrow Function
  3. Adequate renal function
  4. Adequate Liver Function
  5. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk by Investigator judgment.
  6. A histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients intolerant to standard treatment or, resistant to standard therapy* (per NCCN guidelines) or for which no curative therapy is available for the following tumor types:

    - Bladder, Brain, Breast, Cervical, Cholangiocarcinoma, Colorectal, Esophageal, Gastric, Head and Neck, Kidney, Liver, Lung, Melanoma, Ovarian, Pancreatic, Pleural mesothelioma, Prostate, Sarcoma, Tongue cancer, Thymic carcinomas, Urinary tract

  7. At least one measurable lesion (as defined by RECIST version 1.1) that has not been previously irradiated.
  8. An ECOG PS 0 to 2.

Exclusion Criteria:

  1. Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
  2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
  3. Patients with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
  4. Major surgery within 4 weeks prior to study entry.
  5. Radiation therapy within 4 weeks prior to receiving the first QBS10072S dose (bone lesions requiring radiation may be treated with limited radiation therapy during this period).
  6. Systemic anticancer therapy within 4 weeks prior to study entry
  7. Bleeding esophageal or gastric varices <2 months prior to the date of informed consent.
  8. Unmanageable ascites.
  9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results
  10. On therapeutic anticoagulation, except low molecular weight heparin, vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor.
  11. Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsade de Pointes, clinically significant arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock, bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinical significant episode of thromboembolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation).
  12. Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy) or requiring more than two medications for adequate control.

Sites / Locations

  • St George Private Hospital
  • Sydney Southwest Private Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose escalation of QBS10072S

Arm Description

Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.

Outcomes

Primary Outcome Measures

Determination of maximum tolerated dose (MTD)
MTD will be determined by presence of AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.

Secondary Outcome Measures

Safety and tolerability assessed by adverse events and serious adverse events
Safety and tolerability will be determined by adverse events as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Peak Plasma Concentration (Cmax)
Determine the maximum plasma concentration of QBS10072S.
Area under the plasma concentration versus time curve (AUC) of QBS10072S
Determine the plasma concentration of QBS10072S over time.
Half-life of QBS10072S in plasma (t1/2)
Determine the half life of QBS10072S in plasma; the half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.
Time to maximum concentration of QBS10072S in plasma (Tmax)
Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.

Full Information

First Posted
June 2, 2020
Last Updated
January 16, 2023
Sponsor
Quadriga Biosciences, Inc.
Collaborators
Novotech (Australia) Pty Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04430842
Brief Title
Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S
Official Title
A Phase 1, Open Label, Multi-Center, Single and Multiple Dose, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S in Previously Treated Patients With Advanced or Metastatic Cancers With High LAT1 Signatures, and in Patients With Relapsed or Refractory Grade 4 Astrocytoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
July 20, 2020 (Actual)
Primary Completion Date
September 21, 2022 (Actual)
Study Completion Date
December 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Quadriga Biosciences, Inc.
Collaborators
Novotech (Australia) Pty Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a multi-center, open-label, dose escalation study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of QBS10072S in patients with advanced or metastatic cancers with high LAT1 expression. The MTD of QBS10072S will be confirmed in patients with relapsed or refractory grade 4 astrocytoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Astrocytoma, Brain Cancer, Brain Metastases, Bladder Cancer, Breast Cancer, Cervical Cancer, Cholangiocarcinoma, Colorectal Cancer, Esophagus Cancer, Gastric Cancer, Head and Neck Cancer, Kidney Cancer, Liver Cancer, Lung Cancer, Melanoma, Ovarian Cancer, Pancreatic Cancer, Pleural Mesothelioma, Prostate Cancer, Sarcoma, Tongue Cancer, Thymic Carcinoma, Urinary Tract Cancer
Keywords
Phase 1, Dose escalation, Metastatic, Brain metastasis, Brain metastases, GBM, Astrocytoma, Brain tumor, Cancer, Oncology, Glioblastoma, Glioblastoma multiforme, Brain, Neurology, Neuroscience, Headaches, Vomiting, Seizures, Drowsiness, Chemotherapy, Surgery, Radiation, Neuro-oncology, Blurred vision, Loss of appetite, Speech difficulty, Changes in ability to think and learn, Changes in mood and personality, Persistent headaches, Neuropathologist, Magnetic resonance spectroscopy (MRS), Positron emission tomography (PET scan), Intraoperative MRI, Tumor removal, Craniotomy, Standard external beam radiation therapy, Radiosurgery, Temozolomide, Bevacizumab, Avastin, Neurological exam, TMZ

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
The dose escalation scheme for this trial employs an mTPI-2 design.
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose escalation of QBS10072S
Arm Type
Experimental
Arm Description
Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.
Intervention Type
Drug
Intervention Name(s)
QBS10072S
Intervention Description
QBS10072S targets cancers with high LAT1 expression.
Primary Outcome Measure Information:
Title
Determination of maximum tolerated dose (MTD)
Description
MTD will be determined by presence of AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Safety and tolerability assessed by adverse events and serious adverse events
Description
Safety and tolerability will be determined by adverse events as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
Time Frame
28 days
Title
Peak Plasma Concentration (Cmax)
Description
Determine the maximum plasma concentration of QBS10072S.
Time Frame
28 days
Title
Area under the plasma concentration versus time curve (AUC) of QBS10072S
Description
Determine the plasma concentration of QBS10072S over time.
Time Frame
28 days
Title
Half-life of QBS10072S in plasma (t1/2)
Description
Determine the half life of QBS10072S in plasma; the half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.
Time Frame
28 days
Title
Time to maximum concentration of QBS10072S in plasma (Tmax)
Description
Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female participants aged ≥18 years at the time of informed consent. Adequate Bone Marrow Function Adequate renal function Adequate Liver Function Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk by Investigator judgment. A histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients intolerant to standard treatment or, resistant to standard therapy* (per NCCN guidelines) or for which no curative therapy is available for the following tumor types: - Bladder, Brain, Breast, Cervical, Cholangiocarcinoma, Colorectal, Esophageal, Gastric, Head and Neck, Kidney, Liver, Lung, Melanoma, Ovarian, Pancreatic, Pleural mesothelioma, Prostate, Sarcoma, Tongue cancer, Thymic carcinomas, Urinary tract At least one measurable lesion (as defined by RECIST version 1.1) that has not been previously irradiated. An ECOG PS 0 to 2. Exclusion Criteria: Patients with tumor primarily localized to the brainstem or spinal cord. Presence of known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement). Patients with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ. Major surgery within 4 weeks prior to study entry. Radiation therapy within 4 weeks prior to receiving the first QBS10072S dose (bone lesions requiring radiation may be treated with limited radiation therapy during this period). Systemic anticancer therapy within 4 weeks prior to study entry Bleeding esophageal or gastric varices <2 months prior to the date of informed consent. Unmanageable ascites. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results On therapeutic anticoagulation, except low molecular weight heparin, vitamin K antagonists or factor Xa inhibitors may be allowed following discussion with the Sponsor. Any of the following in the previous 6 months: myocardial infarction, congenital long QT syndrome, Torsade de Pointes, clinically significant arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock, bifascicular block, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinical significant episode of thromboembolic disease. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation). Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy) or requiring more than two medications for adequate control.
Facility Information:
Facility Name
St George Private Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Sydney Southwest Private Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia

12. IPD Sharing Statement

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Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S

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