Study Assessing QBS72S For Treating Brain Metastases of Triple Negative Breast Cancer

• Sponsor: Melanie Hayden Gephart (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05305365
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 39
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This study will evaluate whether the chemotherapy agent QBS10072S,a.k.a. QBS72S, is effective and safe as a treatment for two types of brain metastases from triple negative breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases; Breast Cancer	Drug: QBS72S	Phase 2

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

1. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through progression free survival (PFS) in Cohort 1 (Stages 1+2).

2. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall survival (OS) in Cohort 1 (Stages 1+2).

3. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through durations of response (DoR) in Cohort 1 (Stages 1+2).

4. Evaluate safety of QBS72S treatment in Cohort 1 (Stages 1+2), and Cohort 2.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IIa Study Assessing QBS72S For Treating Brain Metastases of Triple Negative Breast Cancer
• Anticipated Study Start Date: Jul 1, 2022
• Anticipated Primary Completion Date: Apr 1, 2024
• Anticipated Study Completion Date: Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QBS72S 12 mg/m2 IV injection All participants will receive QBS72S IV injections once monthly until disease progression.	Drug: QBS72S; QBS72S 12mg/m2 injection given intravenous once a month.; Other Names: QBS10072S

Outcome Measures

Primary Outcome Measures

1. Overall Response against Intracranial Tumor Lesions [6 months]

   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)

2. RECIST 1.1 response criteria [6 months from the start of treatment]

   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

1. Progression-free Survival (PFS) [2 months]

   Progression-free Survival (PFS) means to remain alive without tumor progression, assessed as a ≥ 25% increase in tumor diameter

2. Overall Survival (OS) [2 months]

   Overall survival (OS) refers to remaining alive at the time of the assessment.

3. Duration of Response (DoR) [6 months]

   Duration of Response (DoR) refers to length of time that a clinical response is maintained in Cohort 1 (Stages 1+2) participants.

4. Related Adverse Events (AEs) [30 days following the last administration of study drug]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute	Palo Alto	California	United States	94305

Sponsors and Collaborators

• Melanie Hayden Gephart

Investigators

• Principal Investigator: Melanie H Gephart, MD, MAS, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melanie Hayden Gephart, Professor of Neurosurgery, Stanford University
• ClinicalTrials.gov Identifier: NCT05305365
• Other Study ID Numbers: IRB-63041; BRN0051
• First Posted: Mar 31, 2022
• Last Update Posted: Jun 30, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Triple Negative Breast Neoplasms

Study Results

No Results Posted as of Jun 30, 2022