Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Liposarcoma

Disease Attributes

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Botulinum Toxins, Type A

abobotulinumtoxinA

Epinephrine

Pyrazole

Racepinephrine

Epinephryl borate

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.

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

BTX-A51

Michael Wagner, MD

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)

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.

BTX-A51 in Patients With Liposarcoma

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

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.

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.

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.

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.

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.

Edgewood Oncology Inc.

Michael Wagner

Sponsor Investigator

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Stomach Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Abdominal Neoplasms

Pelvic Neoplasms

Mesothelioma

Mesothelioma, Malignant

Rhabdomyosarcoma

Desmoplastic Small Round Cell Tumor

Lung Neoplasms

Fallopian Tube Neoplasms

Rectal Neoplasms

Colonic Neoplasms

Neoplasms, Glandular and Epithelial

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Myosarcoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Colonic Diseases

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Malignant Mesothelioma

Antineoplastic Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Cisplatin

Daunorubicin

Sodium thiosulfate

Antidotes

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Protective Agents

Antioxidants

Antitubercular Agents

Chelating Agents

Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate IV over 12 hours. Patients also undergo CT scan, MRI or PET/CT scan and blood sample collection throughout study.

Undergo HIPEC with doxorubicin and cisplatin

Cytoreductive Surgery

Hyperthermic Intraperitoneal Chemotherapy

Sodium Thiosulfate

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Biospecimen Collection

Clinical Trial Referral Office

Patricio C. Gargollo, M.D.

This early phase I trial studies how well heated intra-peritoneal chemotherapy with doxorubicin and cisplatin work for the treatment of abdominal or pelvic tumors that can be removed by surgery (resectable), does not respond to treatment (refractory), or has come back (recurrent). Heated intra-peritoneal chemotherapy is a procedure performed in combination with abdominal surgery for cancer that has spread to the abdomen. It involves the infusion of a heated chemotherapy solution that circulates into the abdominal cavity. Chemotherapy drugs, such as doxorubicin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Heating a chemotherapy solution and infusing it directly into the abdomen may kill more cells.

PRIMARY OBJECTIVES:

I. To assess the feasibility of heated intra-peritoneal chemotherapy (HIPEC) with doxorubicin (DOXO) and cisplatin (CDDP) after surgical resection of pediatric pelvic and abdominal tumors.

II. To assess morbidity, hospital length of stay and peri-operative mortality outcomes for pediatric patients with intraperitoneal sarcoma undergoing hyperthermic intraperitoneal chemotherapy.

SECONDARY OBJECTIVE:

I. To assess complications and adverse events of HIPEC. II. Evaluate disease recurrence patterns: locoregional versus distant. III. Evaluate disease progression defined by radio-graphically visible nodules greater than 1.5 cm.

OUTLINE:

Patients undergo cytoreduction. Patients also undergo HIPEC over 60 minutes consisting of doxorubicin and cisplatin. Patients then receive sodium thiosulfate intravenously (IV) over 12 hours.

After completion of the study treatment, patients are followed every 6 months for 5 years.

Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for Abdominal for Pelvic Tumors in Pediatric Patients

A Prospective Study of Heated Intra-Peritoneal Chemotherapy (H.I.P.E.C.) With Doxorubicin and Cisplatin in Pediatric Patients With Pelvic and Abdominal Tumors. The TOAST IT Trial (Trial Of Adjuvant Surgical Treatment With Intraperitoneal Chemotherapy)

To assess the feasibility of heated intra-peritoneal chemotherapy (HIPEC) with doxorubicin (DOXO) and cisplatin (CDDP) after surgical resection of pediatric pelvic and abdominal tumors.

Will be estimated using the Kaplan-Meier method. Patterns of tumor recurrence and survival will be assessed by reviewing routine surveillance imaging. Patient contact may be contacted by telephone.

Patterns of tumor recurrence and survival will be assessed by reviewing routine surveillance imaging. Patient contact may be contacted by telephone.

Will be measured using the Clavien Dindo scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Will be tracked using NCI CTCAE version 5.

The PFS is defined as the time between initiation of protocol treatment and the first occurrence of disease. It will be defined radiologically.

Mayo Clinic

Nervous System Diseases

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Histiocytoma, Malignant Fibrous

Leiomyosarcoma

Nerve Sheath Neoplasms

Neurofibrosarcoma

Histiocytoma

Neoplasms, Nerve Tissue

Nervous System Neoplasms

Peripheral Nervous System Neoplasms

Peripheral Nervous System Diseases

Neuromuscular Diseases

Fibrosarcoma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neurofibromatoses

Neurofibroma

Undifferentiated Pleomorphic Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Neurofibromatosis

Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Alisertib

Laboratory Biomarker Analysis

Mark Dickson

This phase II trial studies how well alisertib works in treating patients with sarcoma that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or has spread to other places in the body (metastatic). Alisertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the response rate (complete response \[CR\] + partial response \[PR\]) assessed for patients within each cohort: liposarcoma (cohort 1); leiomyosarcoma (non-uterine) (cohort 2); undifferentiated sarcoma (including pleomorphic undifferentiated sarcoma, formerly known as malignant fibrous histiocytoma, and myxofibrosarcoma) (cohort 3); malignant peripheral nerve sheath tumor (cohort 4); and other sarcomas (cohort 5).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients treated with MLN8237 (alisertib) in each cohort.

II. To assess the adverse events associated with patients treated with MLN8237 in each cohort.

TERTIARY OBJECTIVES:

I. To correlate potential clinical benefit with markers of aurora kinase inhibition in pre- and post-treatment tumor biopsies.

II. To correlate clinical outcome with change in fluorine F 18 fluorothymidine (FLT)-positron emission tomography (PET) uptake at baseline versus after one week of treatment (ie, week 2 of cycle 1).

OUTLINE:

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 18 months.

Alisertib in Treating Patients With Advanced or Metastatic Sarcoma

Phase II Study of MLN8237 in Advanced/Metastatic Sarcoma

The primary endpoint was estimated by the number of confirmed responses divided by the total number of evaluable patients per cohort. The study used a two stage Simon design to assess the primary endpoint. A confirmed tumor response rate of 5% was considered not promising; an observed confirmed response rate of 25% was considered promising. One confirmed response within the initial 9 patients enrolled within each cohort, expanded enrollment to 24 patients in that cohort. 3 out of 24 patients with confirmed tumor responses was considered evidence that this treatment could be recommended for further testing. This study design yielded 90% power to detect a true confirmed response rate of at least 25% at .10 level of significance if the true rate is at most 5%. There was a 63% chance of stopping early if the true confirmed response rate was 5%.

The distribution will be estimated by the methods of Kaplan and Meier. The estimates of survival at specific time points will be calculated (eg, median, 6 month survival).

The distribution will be estimated by the methods of Kaplan and Meier. The estimates of PFS at specific time points will be calculated (eg, median, 1 year PFS).

Adverse Events: Incidence of adverse events, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events were collected every cycle during treatment and up to one month after treatment. Adverse events were summarized using summary statistics and frequency tables for each separate cohort. Per protocol, analysis was descriptive in nature. In this section, the number of patients that reported a grade 4 or higher event are summarized. A complete listing of Adverse Events is provided in the Adverse Events section below.

National Cancer Institute (NCI)

Liposarcoma patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohort 1

Leiomyosarcoma patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohort 2

Undifferentiated Sarcoma patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohort 3

Malignant Peripheral Nerve Sheath Tumor patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohort4

Other Sarcoma patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohort 5

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Mark Andrew Dickson M.D.

Cohort 4

The Primary Endpoint for This Trial Was the Percent of Confirmed Tumor Responses. Confirmed Tumor Response to Treatment Was Defined as a Complete or Partial Response(Per RECIST 1.1) on Two Consecutive Evaluations at Least 6 Weeks Apart.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BTX-A51 in Patients With Liposarcoma	NCT06414434	Liposarcoma Recurrent Lipos... Metastatic Lipo... Unresectable Li... MDM2 Gene Ampli...	BTX-A51	18 Years -	Dana-Farber Cancer Institute
Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for Abdominal for Pelvic Tumors in Pediatric Patients	NCT04213794	Malignant Abdom... Malignant Pelvi... Recurrent Colon... Recurrent Desmo... Recurrent Fallo... Recurrent Gastr... Recurrent Lipos... Recurrent Malig... Recurrent Ovari... Recurrent Prima... Recurrent Recta... Recurrent Rhabd... Recurrent Sarco... Refractory Colo... Refractory Desm... Refractory Fall... Refractory Gast... Refractory Lipo... Refractory Mali... Refractory Ovar... Refractory Prim... Refractory Rect... Refractory Rhab... Refractory Sarc... Resectable Lipo... Resectable Mali... Resectable Sarc...	Cisplatin Cytoreductive S... Doxorubicin Hyperthermic In... Sodium Thiosulf... Computed Tomogr... Magnetic Resona... Positron Emissi... Biospecimen Col...	1 Year - 25 Years	Mayo Clinic
Alisertib in Treating Patients With Advanced or Metastatic Sarcoma	NCT01653028	Myxofibrosarcom... Recurrent Adult... Recurrent Leiom... Recurrent Lipos... Recurrent Malig... Recurrent Undif... Stage III Soft ... Stage IV Soft T...	Alisertib Laboratory Biom...	18 Years -	National Cancer Institute (NCI)
Heated Intra-peritoneal Chemotherapy With Doxorubicin and Cisplatin for Abdominal for Pelvic Tumors in Pediatric Patients	NCT04213794	Malignant Abdom... Malignant Pelvi... Recurrent Colon... Recurrent Desmo... Recurrent Fallo... Recurrent Gastr... Recurrent Lipos... Recurrent Malig... Recurrent Ovari... Recurrent Prima... Recurrent Recta... Recurrent Rhabd... Recurrent Sarco... Refractory Colo... Refractory Desm... Refractory Fall... Refractory Gast... Refractory Lipo... Refractory Mali... Refractory Ovar... Refractory Prim... Refractory Rect... Refractory Rhab... Refractory Sarc... Resectable Lipo... Resectable Mali... Resectable Sarc...	Cisplatin Cytoreductive S... Doxorubicin Hyperthermic In... Sodium Thiosulf... Computed Tomogr... Magnetic Resona... Positron Emissi... Biospecimen Col...	1 Year - 25 Years	Mayo Clinic

Spots Global Cancer Trial Database for recurrent liposarcoma