Clinical trial NCT04430842: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Quadriga Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2020-06-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The dose escalation scheme for this trial employs an mTPI-2 design.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Determination of maximum tolerated dose (MTD)
timeFrame: 28 days
Secondary outcomes:
measure: Safety and tolerability assessed by adverse events and serious adverse events
timeFrame: 28 days
measure: Peak Plasma Concentration (Cmax)
timeFrame: 28 days
measure: Area under the plasma concentration versus time curve (AUC) of QBS10072S
timeFrame: 28 days
measure: Half-life of QBS10072S in plasma (t1/2)
timeFrame: 28 days
measure: Time to maximum concentration of QBS10072S in plasma (Tmax)
timeFrame: 28 days
Other outcomes:
Locations:
city: Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Sydney Southwest Private Hospital
state: New South Wales
Study officials:
References: