## Protocol Section
### Identification Module
**NCT ID:** NCT06414434

**Brief Title:** BTX-A51 in Patients With Liposarcoma

**Official Title:** A Pilot Study of BTX-A51 in Patients With Metastatic and/or Recurrent Liposarcomas Characterized by MDM2 Amplifications

#### Organization Study ID Info
**ID:** 24-156
#### Organization
**Class:** OTHER
**Full Name:** Dana-Farber Cancer Institute
### Status Module
#### Completion Date
**Date:** 2027-06-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-11

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Edgewood Oncology Inc.

#### Lead Sponsor

**Class:** OTHER

**Name:** Michael Wagner

#### Responsible Party

**Investigator Affiliation:** Dana-Farber Cancer Institute

**Investigator Full Name:** Michael Wagner

**Investigator Title:** Sponsor Investigator

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study is testing if the recommended dose of BTX-A51 is safe and tolerable in participants with liposarcoma.

The name of the study drug used in this research study is:

-BTX-A51 (a type of kinase inhibitor)

**Detailed Description:** This is a single arm, pilot study assessing the safety and preliminary exploration of BTX-A51 in participants with metastatic and/or recurrent liposarcomas characterized by Murine Double Minute Clone 2 (MDM2) amplifications. BTX-A51 works in a different way from currently approved therapies used to treat liposarcoma by blocking proteins called CK1α and CDK9.

The U.S. Food and Drug Administration (FDA) has not approved BTX-A51 as a treatment for Liposarcoma.

The research study procedures include screening for eligibility, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission Tomography (PET) scans, blood tests, and tumor biopsies.

Participants will receive study treatment for as long as there are no serious side effects, and disease does not get worse. Participants will be followed for 1 year after the last dose of BTX-A51.

It is expected that about 12 people will take part in this research study.

Edgewood Oncology is supporting this research study by providing the study drug.

### Conditions Module

**Conditions:**

- Liposarcoma

- Recurrent Liposarcoma

- Metastatic Liposarcoma

- Unresectable Liposarcoma

- MDM2 Gene Amplification

**Keywords:**

- Liposarcoma

- Recurrent Liposarcoma

- Metastatic Liposarcoma

- Unresectable Liposarcoma

- MDM2 Gene Amplification

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 12

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will be enrolled and will complete study procedures as follows:

* Baseline visit with tumor biopsy.
* Tumor biopsy at the end of Cycle 1.
* Radiologic imaging every 2 cycles.
* Cycle 1 through End of Treatment:

  --Day 1 of 28 day cycle: Predetermined dose of BTX-A51 3x weekly.
* End of Treatment visit with radiologic imaging.
* Follow-up: every 3 months for 1 year.

**Intervention Names:**

- Drug: BTX-A51

**Label:** BTX-A51

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- BTX-A51

**Description:** Multi-kinase inhibitor, 1.0 mg, 2.0 mg, and 7.0 mg immediate-release capsules, taken orally per protocol.

**Name:** BTX-A51

**Other Names:**

- C32H41ClN6O6S2

- (1r,4r)-N 1-(5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-l H pyrazol-3-yl)pyrimidin-2-yl)cyclohexane-l ,4-diamine bis(4-methylbenzenesulfonate),

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Safety and tolerability will be monitored through continuous reporting of treatment-emergent and treatment-related adverse events, laboratory abnormalities, and incidence of subjects experiencing dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event. Toxicities are to be assessed according to the CTCAEv5.

**Measure:** Number of participants with adverse events, with laboratory abnormalities, with dose modifications, delays, interruptions, or premature discontinuation of BTX-A51 due to an adverse event

**Time Frame:** All AEs will be recorded from the time the subject signs informed consent until 30 days after the last dose of study BTX-A51.

#### Secondary Outcomes

**Description:** The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECISTv1.1 criteria.

**Measure:** Overall Response Rate (ORR)

**Time Frame:** ORR expected to be observed up to 3 years

**Description:** 1-year PFS is a probability estimated using progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.

**Measure:** 1-year Progression-Free Survival (PFS) Rate

**Time Frame:** 1 year

**Description:** 1-year OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.

**Measure:** 1-year Overall Survival (OS)

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Study participants must have histologically-confirmed metastatic and/or recurrent liposarcoma (limited to the subtypes of well-differentiated and/or dedifferentiated liposarcoma, which are associated with MDM2 amplifications).
* ECOG performance status ≤2
* Adequate organ and marrow function as defined by the following metrics resulted within 7 days of study enrollment:

  * WBC \>3000/mm3
  * Platelets \>75,000μl
  * ANC \>1500μl
  * Hgb \>9g/dl
  * Creatinine \<1.5 x ULN or measured CrCl of \>60ml/m2/1.73 m2
  * Total bilirubin \<2 x ULN
  * AST/ALT \<3 x ULN
* Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as

  ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
* Patients must have recovered from toxicity related to prior therapy to grade \<=1 (defined by CTCAE v5.0) (except alopecia and neuropathy, or immunotherapy related hypothyroidism)
* As the effect of this study drug on the developing human fetus is not known, women of child-bearing potential and men must agree to use at least 2 methods of contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion.
* Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment.
* Ability to understand and the willingness to sign a written informed consent document.
* Age ≥18 years
* Patients must have completed all prior anti-cancer treatment for liposarcoma, including radiation, ≥ 14 days prior to registration.

Exclusion Criteria:

* Patient with current evidence of active and uncontrolled infection, NYHA Class III-IV CHF, documented Child's class B-C cirrhosis, or uncontrolled medical disease which in the opinion of the investigator or the sponsor could compromise safety and/or assessment of efficacy.
* Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative PCR result before enrollment; those who are PCR positive will be excluded.
* Major surgical procedure or open surgical biopsy within 28 days of first dose of study drug
* Active central nervous system (CNS) disease involvement, or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity. Subject with known CNS metastases that are treated and stable (without evidence of CNS toxicity) and are not requiring systemic steroids are allowed to be enrolled.
* Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Myocardial infarction within 12 months of screening
* Use of any other concurrent investigational agents or anticancer agents, excluding hormonal therapy for breast or prostate cancer
* Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BTX- A51, breastfeeding should be discontinued if the mother is treated with BTX-A51.
* Inability to swallow pills or inadequate GI absorption in the opinion of the treating investigator.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** MICHAEL_WAGNER@DFCI.HARVARD.EDU

**Name:** Michael Wagner, MD

**Phone:** 617-632-5204

**Role:** CONTACT

**Contact 2:**

**Email:** MICHAEL_WAGNER@DFCI.HARVARD.EDU

**Name:** Michael Wagner, MD

**Phone:** 617-632-3352

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** michael_wagner@dfci.harvard.edu

- **Name:** Michael Wagner, MD

- **Phone:** 617-632-3352

- **Role:** CONTACT

***Contact 2:***

- **Name:** Michael Wagner, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Brigham and Women's Hospital

**State:** Massachusetts

**Zip:** 02215

**Location 2:**

**City:** Boston

**Contacts:**

***Contact 1:***

- **Email:** michael_wagner@dfci.harvard.edu

- **Name:** Michael Wagner, MD

- **Phone:** 617-632-3352

- **Role:** CONTACT

***Contact 2:***

- **Name:** Michael Wagner, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Dana-Farber Cancer Institute

**State:** Massachusetts

**Zip:** 02215

#### Overall Officials

**Official 1:**

**Affiliation:** Dana-Farber Cancer Institute

**Name:** Michael Wagner, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

**Description:** The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

**Info Types:**

- STUDY_PROTOCOL

- SAP

**IPD Sharing:** YES

**Time Frame:** Data can be shared no earlier than 1 year following the date of publication

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000018205

- Term: Neoplasms, Adipose Tissue

- ID: D000018204

- Term: Neoplasms, Connective and Soft Tissue

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000012509

- Term: Sarcoma

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11080

- Name: Liposarcoma

- Relevance: HIGH

- As Found: Liposarcoma

- ID: M14850

- Name: Recurrence

- Relevance: HIGH

- As Found: Recurrent

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M20351

- Name: Neoplasms, Adipose Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M20350

- Name: Neoplasms, Connective and Soft Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M15327

- Name: Sarcoma

- Relevance: LOW

- As Found: Unknown

- ID: T3479

- Name: Liposarcoma

- Relevance: HIGH

- As Found: Liposarcoma

- ID: T5284

- Name: Soft Tissue Sarcoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008080

- Term: Liposarcoma

- ID: D000012008

- Term: Recurrence

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaCoAg

- Name: Vasoconstrictor Agents

- Abbrev: Resp

- Name: Respiratory System Agents

### Intervention Browse Module - Browse Leaves

- ID: M21257

- Name: Botulinum Toxins, Type A

- Relevance: LOW

- As Found: Unknown

- ID: M250193

- Name: abobotulinumtoxinA

- Relevance: LOW

- As Found: Unknown

- ID: M7992

- Name: Epinephrine

- Relevance: LOW

- As Found: Unknown

- ID: M198097

- Name: Pyrazole

- Relevance: LOW

- As Found: Unknown

- ID: M30371

- Name: Racepinephrine

- Relevance: LOW

- As Found: Unknown

- ID: M211043

- Name: Epinephryl borate

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
