NCT04430842

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jul 2020

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 2, 2020

Completed
10 days until next milestone

First Posted

Study publicly available on registry

June 12, 2020

Completed
1 month until next milestone

Study Start

First participant enrolled

July 20, 2020

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 21, 2022

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 22, 2022

Completed
Last Updated

January 18, 2023

Status Verified

January 1, 2023

Enrollment Period

2.2 years

First QC Date

June 2, 2020

Last Update Submit

January 16, 2023

Conditions

AstrocytomaBrain CancerBrain MetastasesBladder CancerBreast CancerCervical CancerCholangiocarcinomaColorectal CancerEsophagus CancerGastric CancerHead and Neck CancerKidney CancerLiver CancerLung CancerMelanomaOvarian CancerPancreatic CancerPleural MesotheliomaProstate CancerSarcomaTongue CancerThymic CarcinomaUrinary Tract Cancer

Keywords

Phase 1Dose escalationMetastaticBrain metastasisBrain metastasesGBMAstrocytomaBrain tumorCancerOncologyGlioblastomaGlioblastoma multiformeBrainNeurologyNeuroscienceHeadachesVomitingSeizuresDrowsinessChemotherapySurgeryRadiationNeuro-oncologyBlurred visionLoss of appetiteSpeech difficultyChanges in ability to think and learnChanges in mood and personalityPersistent headachesNeuropathologistMagnetic resonance spectroscopy (MRS)Positron emission tomography (PET scan)Intraoperative MRITumor removalCraniotomyStandard external beam radiation therapyRadiosurgeryTemozolomideBevacizumabAvastinNeurological examTMZ

Outcome Measures

Primary Outcomes (1)

  • 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.

    28 days

Secondary Outcomes (5)

  • Safety and tolerability assessed by adverse events and serious adverse events

    28 days

  • Peak Plasma Concentration (Cmax)

    28 days

  • Area under the plasma concentration versus time curve (AUC) of QBS10072S

    28 days

  • Half-life of QBS10072S in plasma (t1/2)

    28 days

  • Time to maximum concentration of QBS10072S in plasma (Tmax)

    28 days

Study Arms (1)

Dose escalation of QBS10072S

EXPERIMENTAL

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

Drug: QBS10072S

Interventions

QBS10072SDRUG

QBS10072S targets cancers with high LAT1 expression.

Dose escalation of QBS10072S

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

Sydney Southwest Private Hospital

Liverpool, New South Wales, 2170, Australia

Location

MeSH Terms

Conditions

AstrocytomaBrain NeoplasmsUrinary Bladder NeoplasmsBreast NeoplasmsUterine Cervical NeoplasmsCholangiocarcinomaColorectal NeoplasmsEsophageal NeoplasmsStomach NeoplasmsHead and Neck NeoplasmsKidney NeoplasmsLiver NeoplasmsLung NeoplasmsMelanomaOvarian NeoplasmsPancreatic NeoplasmsMesothelioma, MalignantProstatic NeoplasmsSarcomaTongue NeoplasmsThymomaUrologic NeoplasmsNeoplasm MetastasisNeoplasmsGlioblastomaHeadacheVomitingSeizuresSleepinessAnorexiaSpeech Disorders

Condition Hierarchy (Ancestors)

GliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCentral Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesUterine NeoplasmsGenital Neoplasms, FemaleUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleGenital DiseasesAdenocarcinomaCarcinomaIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesEsophageal DiseasesStomach DiseasesKidney DiseasesLiver DiseasesRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesNeuroendocrine TumorsNevi and MelanomasSkin NeoplasmsEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesEndocrine System DiseasesGonadal DisordersPancreatic DiseasesMesotheliomaAdenomaNeoplasms, MesothelialPleural NeoplasmsGenital Neoplasms, MaleGenital Diseases, MaleProstatic DiseasesNeoplasms, Connective and Soft TissueMouth NeoplasmsMouth DiseasesStomatognathic DiseasesTongue DiseasesNeoplasms, Complex and MixedThymus NeoplasmsLymphatic DiseasesHemic and Lymphatic DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsPainNeurologic ManifestationsSigns and SymptomsSigns and Symptoms, DigestiveLanguage DisordersCommunication DisordersNeurobehavioral Manifestations

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: The dose escalation scheme for this trial employs an mTPI-2 design.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2020

First Posted

June 12, 2020

Study Start

July 20, 2020

Primary Completion

September 21, 2022

Study Completion

December 22, 2022

Last Updated

January 18, 2023

Record last verified: 2023-01

Locations

AU(2)