Evaluation of Abemaciclib and Radiation Therapy Before Surgery for the Treatment of High-Risk Adipocytic Retroperitoneal Sarcoma

NCT06025747 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1123382NCI-2023-05595FHIRB0020212
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of abemaciclib and how well it works with radiation therapy before surgery in treating patients with high-risk adipocytic retroperitoneal sarcoma. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving abemaciclib together with radiation therapy before surgery may shrink tumors in patients with high-risk adipocytic retroperitoneal sarcoma.

Conditions

Retroperitoneal Sarcoma

Outcome Measures

Primary Outcomes (1)

• Recommended phase 2 dose of abemaciclib in combination with radiation

  Up to 28 days

Secondary Outcomes (4)

• Rate of pathologic response

  Up to 2 years

• Rate of surgical excision with negative margins

  Up to 2 years

• Incidence of adverse events

  Up to 30 days post treatment

• Rate of discontinuation of abemaciclib monotherapy

  Within the first 15 days (+7 days) of Cycle 1 Day 1 (Cycle is 28 days)

Study Arms (1)

Treatment (abemaciclib, radiation therapy, surgery)

EXPERIMENTAL

Prior to surgery, patients receive abemaciclib orally PO BID on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy over 28 fractions starting on cycle 1 day 15 in the absence of disease progression or unacceptable toxicity. After completion of radiation therapy, patients may undergo surgery. Patients also undergo CT or MRI during screening and on study.

Drug: Abemaciclib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Radiation: Radiation Therapy; Procedure: Therapeutic Surgical Procedure

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (abemaciclib, radiation therapy, surgery)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (abemaciclib, radiation therapy, surgery)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (abemaciclib, radiation therapy, surgery)

Therapeutic Surgical Procedure PROCEDURE

Undergo surgery

Treatment (abemaciclib, radiation therapy, surgery)

Abemaciclib DRUG

Given PO

Also known as: LY-2835219, LY2835219, Verzenio

Treatment (abemaciclib, radiation therapy, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects, \>= 18 years old, must have newly diagnosed or locally recurrent MDM2 or CDK4-amplified adipocytic sarcoma as determined by fluorescence in situ hybridization (FISH), or other clinically appropriate methodology in the opinion of the reviewing pathologist. Histologic or imaging evidence of the presence of a dedifferentiated component must be present
• Subjects must have one or more measurable target lesions by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), assessed via CT scan or MRI
• At the time of study enrollment, subjects must have a tumor burden that is judged to be surgically resectable
• Have plans to undergo neoadjuvant radiation therapy followed by surgical resection. Review and approval of final treatment plans for subjects receiving radiotherapy locally/at an outside institution must be reviewed and approved by a radiation oncologist investigator prior to initiation of radiotherapy
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (\>= 1.5 GI/L) without granulocyte colony-stimulating factor support in the last 14 days (subjects may not have received blood product transfusion or granulocyte colony-stimulating factor \[G-CSF\] within 14 days prior to screening)
• White blood cell count \>= 2500/mm\^3 (\>= 2.5 GI/L) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Platelets \>= 100,000/mm\^3 (\>= 100 GI/L) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Hemoglobin \>= 8 g/dL (\>= 80 g/L) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (subjects with Gilbert's disease =\< 2 x ULN and direct bilirubin within normal limits are permitted) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Serum albumin \>= 2.8 g/dl (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Serum creatinine =\< 2.0 x ULN or calculated creatinine clearance \>= 30 mL/min (\>= 0.5 mL/sec) using the Cockcroft-Gault equation (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Urine protein/creatinine ratio (UPCR) =\< 1 mg/mg (=\< 113.2 mg/mmol) (subjects may not have received blood product transfusion or G-CSF within 14 days prior to screening)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Male or non-pregnant and non-breast feeding female:

You may not qualify if:

• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) for the investigational diagnosis
• Receipt of any prior radiation therapy for any reason to the affected area
• Known central nervous system (CNS) metastases
• Evidence of distant metastatic disease at time of treatment initiation
• History of thromboembolic event within 1 year of treatment initiation. Thromboembolic events include, but are not limited to, deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis
• History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
• History of any major surgery within 14 days prior to enrollment
• Receipt of ongoing anti-coagulation for treatment or prophylaxis of thromboembolic event in the setting of prior thromboembolic event
• History of interstitial lung disease
• Subjects with serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \< 30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
• Pregnant or lactating females
• Inability to swallow tablets
• Previously identified allergy or hypersensitivity to components of the study treatment formulations
• Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized tumors deemed cured and not treated with systemic therapy
• Concurrent use of medications (especially those interacting with CYP3A) that potentially interact unsafely with abemaciclib which cannot be discontinued or substituted

Sponsors & Collaborators

• University of Washington: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

abemaciclib; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Therapeutics; Physical Phenomena

Study Officials

• Jeremy Sharib, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Siu

CONTACT

206-606-2465; dsiu@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: September 6, 2023
• Study Start: March 19, 2025
• Primary Completion (Estimated): March 3, 2027
• Study Completion (Estimated): March 3, 2029
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)