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Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer

Primary Purpose

Brain Metastases, Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
QBS72S
Sponsored by
Melanie Hayden Gephart
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases

Eligibility Criteria

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

Inclusion Criteria:

  • The participant must have a histologically confirmed TNBC primary tumor, either confirmed via primary specimen or via metastasis site, having developed brain metastases (parenchymal or LM) after a prior cytotoxic chemotherapy regimen. TNBC is defined as breast cancer that is estrogen receptor (ER)-negative (< 5% expression); progesterone receptor (PR)-negative (< 5% expression); and human epidermal growth factor receptor 2 (HER2)-negative (negative FISH result or a HER2 receptor IHC result of 0 or 1+).There is no restriction on prior cycles of systemic therapy for metastatic breast cancer.
  • One of the following:

    1. A participant with brain parenchymal tumors must have at least one untreated tumor > 3 mm2 that can be seen on 2 or more separate acquired sequences.
    2. A participant with LM disease must have a positive cytology or MRI evidence of LMD. The presence of parenchymal brain metastases does not exclude these participants from Cohort 2.
  • The participant must be 18 years old or older.
  • The participant must have a Karnofsky Performance Status (KPS) of 60 or above.
  • The participant must receive an MRI with contrast that supports the presence of parenchymal brain metastases or leptomeningeal disease.
  • The participant must be on stable doses of corticosteroids and anticonvulsants for greater than or equal to 5 days prior to obtaining the baseline Gd-MRI of the brain.
  • The participant must have completed treatment greater than or equal to:

    1. 14 days for small molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors
    2. 21 days for checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab, and bevacizumab, and cytotoxic chemotherapy
    3. 28 days for investigational drugs and radiotherapy; or
    4. 1 dosing cycle for other interventions, prior to first dose of QBS72S All clinically significant toxicities excluding alopecia must have resolved to less than or equal to CTCAE v5.0 Grade 1. Participation in long term follow up is allowed if no procedures will be performed which may interfere with the interpretation of study results.
  • The participant must have adequate bone marrow function, including:

    1. ANC ≥ 1,500/mm3 or ≥ 1.5 x 109/L
    2. Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L
    3. Hemoglobin ≥ 9 g/dL
  • The participant must have adequate renal function, including serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately.
  • The participant must have adequate liver function, including:

    1. Total serum bilirubin ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a total bilirubin < 3.0 mg/dl
    2. Aspartate and Alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor
  • Any participant physiologically capable of becoming pregnant or getting a partner pregnant must agree to use highly effective contraception during study treatment and for 7 months after study discontinuation.
  • Participants or their designated advocates must be willing to and capable of providing informed consent and willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion Criteria:

  • Participants currently using any anticancer therapy (including radiotherapy) or using any investigational agent(s), except those explicitly documented allowable by the PI.
  • Participants 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.
  • Participants taking a dexamethasone dose greater than 8 mg per day as a stable or decreasing dose. No escalation of dexamethasone dosing is allowed in the past 14 days prior to screening.
  • Participants who received major surgery or brain surgery within 28 days or fewer. Minor procedures such as tumor biopsy are allowed with written approval of the PI.
  • Participants with tumors within the brainstem or spinal cord parenchyma. LMD is not an exclusion criterion.
  • Participants with intolerance to or who have had a severe (Grade 3) allergic or anaphylactic reaction to any of the substances included in the investigational product: sulfobutylether-β-cyclodextrin, melphalan, bendamustine, chlorambucil or any nitrogen mustard chemotherapeutics.
  • Participants who currently use or have an anticipated need for a contraindicated medication including live vaccines, natalizumab, nivolumab, ocrelizumab, palifermin, pimecrolimus, tacrolimus, tofacitinib, and EIAEDs, including phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, and oxcarbazepine. The washout period for any live vaccine is 30 days prior to enrollment. There is no restriction for seasonal flu vaccines that do not contain live virus, nor any approved COVID vaccine.
  • Participants who are pregnant or breastfeeding.
  • Participants who have active medical or psychiatric conditions which, in the opinion of the Principal Investigator or a Sub-Investigator, would compromise or interfere with their ability to participate in the study

Sites / Locations

  • Stanford Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

QBS72S 12 mg/m2 IV injection

Arm Description

All participants will receive QBS72S IV injections once monthly until disease progression.

Outcomes

Primary Outcome Measures

Overall Response against Intracranial Tumor Lesions
The overall response against the target intracranial tumor lesions in Cohort 1 (Stages 1+2) participants was assessed by according to the modified Response Assessment in Neuro-oncology for Brain Metastases (mRANO-BM)
RECIST 1.1 response criteria
Clinical response means either a complete response (CR) or a partial response (PR). CR is defined as disappearance of tumor lesions, and PR is defined as ≥ 30% reduction in diameter of tumor lesions.

Secondary Outcome Measures

Progression-free Survival (PFS)
Progression-free Survival (PFS) means to remain alive without tumor progression, assessed as a ≥ 25% increase in tumor diameter
Overall Survival (OS)
Overall survival (OS) refers to remaining alive at the time of the assessment.
Duration of Response (DoR)
Duration of Response (DoR) refers to length of time that a clinical response is maintained in Cohort 1 (Stages 1+2) participants.
Related Adverse Events (AEs)

Full Information

First Posted
March 22, 2022
Last Updated
January 27, 2023
Sponsor
Melanie Hayden Gephart
Collaborators
Quadriga Biosciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05305365
Brief Title
Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer
Official Title
A Phase IIa Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 16, 2022 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Melanie Hayden Gephart
Collaborators
Quadriga Biosciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is to evaluate the efficacy and safety of QBS72S in participants with advanced, relapsed, metastatic breast cancer with CNS involvement.
Detailed Description
Primary Objective 1. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall response rate (ORR) in Cohort 1 (Stages 1+2). Secondary Objectives Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through progression free survival (PFS) in Cohort 1 (Stages 1+2). Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall survival (OS) in Cohort 1 (Stages 1+2). Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through durations of response (DoR) in Cohort 1 (Stages 1+2). Evaluate safety of QBS72S treatment in Cohort 1 (Stages 1+2), and Cohort 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases, Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
QBS72S 12 mg/m2 IV injection
Arm Type
Experimental
Arm Description
All participants will receive QBS72S IV injections once monthly until disease progression.
Intervention Type
Drug
Intervention Name(s)
QBS72S
Other Intervention Name(s)
QBS10072S
Intervention Description
QBS72S 12mg/m2 injection given intravenous once a month.
Primary Outcome Measure Information:
Title
Overall Response against Intracranial Tumor Lesions
Description
The overall response against the target intracranial tumor lesions in Cohort 1 (Stages 1+2) participants was assessed by according to the modified Response Assessment in Neuro-oncology for Brain Metastases (mRANO-BM)
Time Frame
6 months
Title
RECIST 1.1 response criteria
Description
Clinical response means either a complete response (CR) or a partial response (PR). CR is defined as disappearance of tumor lesions, and PR is defined as ≥ 30% reduction in diameter of tumor lesions.
Time Frame
6 months from the start of treatment
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Progression-free Survival (PFS) means to remain alive without tumor progression, assessed as a ≥ 25% increase in tumor diameter
Time Frame
2 months
Title
Overall Survival (OS)
Description
Overall survival (OS) refers to remaining alive at the time of the assessment.
Time Frame
2 months
Title
Duration of Response (DoR)
Description
Duration of Response (DoR) refers to length of time that a clinical response is maintained in Cohort 1 (Stages 1+2) participants.
Time Frame
6 months
Title
Related Adverse Events (AEs)
Time Frame
30 days following the last administration of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The participant must have a histologically-confirmed breast cancer primary tumor, either confirmed via primary specimen or via metastasis site, having developed brain metastases (parenchymal or LM) after a prior cytotoxic chemotherapy regimen. There is no restriction on prior cycles of systemic therapy for metastatic breast cancer One of the following: A participant with brain parenchymal tumors must have at least one untreated tumor > 3 mm2 that can be seen on 2 or more separate acquired sequences. A participant with LM disease must have a positive cytology or MRI evidence of LMD. The presence of parenchymal brain metastases does not exclude these participants from Cohort 2. The participant must be 18 years old or older. The participant must have a Karnofsky Performance Status (KPS) of 60 or above. The participant must receive an MRI with contrast that supports the presence of parenchymal brain metastases or leptomeningeal disease. The participant must be on stable doses of corticosteroids and anticonvulsants for greater than or equal to 5 days prior to obtaining the baseline Gd-MRI of the brain. The participant must have completed treatment greater than or equal to: 14 days for small molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors 21 days for checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab, and bevacizumab, and cytotoxic chemotherapy 28 days for investigational drugs and radiotherapy; or 1 dosing cycle for other interventions, prior to first dose of QBS72S All clinically significant toxicities excluding alopecia must have resolved to less than or equal to CTCAE v5.0 Grade 1. Participation in long term follow up is allowed if no procedures will be performed which may interfere with the interpretation of study results. The participant must have adequate bone marrow function, including: ANC ≥ 1,500/mm3 or ≥ 1.5 x 109/L Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL The participant must have adequate renal function, including serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately. The participant must have adequate liver function, including: Total serum bilirubin ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a total bilirubin < 3.0 mg/dl Aspartate and Alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor Any participant physiologically capable of becoming pregnant or getting a partner pregnant must agree to use highly effective contraception during study treatment and for 7 months after study discontinuation. Participants or their designated advocates must be willing to and capable of providing informed consent and willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Exclusion Criteria: Participants currently using any anticancer therapy (including radiotherapy) or using any investigational agent(s), except those explicitly documented allowable by the PI. Participants 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. Participants taking a dexamethasone dose greater than 8 mg per day as a stable or decreasing dose. No escalation of dexamethasone dosing is allowed in the past 14 days prior to screening. Participants who received major surgery or brain surgery within 28 days or fewer. Minor procedures such as tumor biopsy are allowed with written approval of the PI. Participants with intolerance to or who have had a severe (Grade 3) allergic or anaphylactic reaction to any of the substances included in the investigational product: sulfobutylether-β-cyclodextrin, melphalan, bendamustine, chlorambucil or any nitrogen mustard chemotherapeutics. Participants who currently use or have an anticipated need for a contraindicated medication including live vaccines, natalizumab, nivolumab, ocrelizumab, palifermin, pimecrolimus, tacrolimus, tofacitinib, and EIAEDs, including phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, and oxcarbazepine. The washout period for any live vaccine is 30 days prior to enrollment. There is no restriction for seasonal flu vaccines that do not contain live virus, nor any approved COVID vaccine. Participants who are pregnant or breastfeeding. Participants who have active medical or psychiatric conditions which, in the opinion of the Principal Investigator or a Sub-Investigator, would compromise or interfere with their ability to participate in the study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Monica Granucci
Phone
650-388-8906
Email
migranucci@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melanie H Gephart, MD, MAS
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Cancer Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monica Granucci
Phone
650-388-8906
Email
migranucci@stanford.edu
First Name & Middle Initial & Last Name & Degree
Melanie H Gephart, MD, MAS
First Name & Middle Initial & Last Name & Degree
Michael Iv, MD
First Name & Middle Initial & Last Name & Degree
Seema Nagpal, MD
First Name & Middle Initial & Last Name & Degree
Michael Lim, MD
First Name & Middle Initial & Last Name & Degree
Gordon Li, MD
First Name & Middle Initial & Last Name & Degree
Steven Chang, MD
First Name & Middle Initial & Last Name & Degree
Lawrence Shuer, MD
First Name & Middle Initial & Last Name & Degree
Lawrence Recht, MD
First Name & Middle Initial & Last Name & Degree
Reena Thomas, MD
First Name & Middle Initial & Last Name & Degree
Chirag Patel, MD
First Name & Middle Initial & Last Name & Degree
Melinda Telli, MD
First Name & Middle Initial & Last Name & Degree
Michelle Melisko, MD

12. IPD Sharing Statement

Learn more about this trial

Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer

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