Pre-Surgery Abemaciclib + Radiation for Retroperitoneal Sarcoma

Overseen By David Siu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must not be taking: CYP3A interactors

Disqualifiers: CNS metastases, Metastatic disease, Thromboembolic events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining the drug abemaciclib with radiation therapy before surgery for high-risk retroperitoneal sarcoma, a cancer in the abdominal area. Abemaciclib may inhibit cancer cell growth, while radiation therapy uses high-energy x-rays to destroy tumor cells. Together, they might shrink tumors before surgery. Individuals diagnosed with adipocytic sarcoma in the abdominal area, planning for radiation and surgery, and whose tumors are deemed surgically removable, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking medications that interact with abemaciclib, especially those affecting CYP3A, you may need to discontinue or substitute them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that abemaciclib, the main focus of this study, has produced promising results in treating certain types of sarcomas. One study found that 74% of patients with dedifferentiated liposarcoma did not experience cancer progression 12 weeks after starting treatment with abemaciclib. This suggests the drug can be effective and is generally well-tolerated by many patients.

Radiation therapy, used alongside abemaciclib in this trial, is a common treatment for various cancers, including sarcomas. Research has shown that pre-surgery radiation can help control cancer growth and improve patient outcomes.

As this trial is in its early stages, it primarily focuses on determining the safest dose and monitoring side effects. While there is limited information about long-term safety and effectiveness, the early results are encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for retroperitoneal sarcoma, which often involve surgery and radiation, abemaciclib introduces a novel approach by using a targeted therapy that inhibits CDK4 and CDK6. These proteins are crucial for tumor cell division, so blocking them can slow down or even stop the growth of cancer cells. Researchers are excited about abemaciclib because it could enhance the effectiveness of radiation therapy, potentially shrinking tumors more effectively before surgery and improving surgical outcomes. This combination might offer a more powerful and precise treatment option for patients with retroperitoneal sarcoma.

What evidence suggests that this trial's treatments could be effective for high-risk adipocytic retroperitoneal sarcoma?

This trial will evaluate the combination of abemaciclib and radiation therapy before surgery for patients with retroperitoneal sarcoma. Studies have shown that abemaciclib, a drug that inhibits enzymes necessary for cancer cell growth, can shrink tumors in certain cancers, such as breast cancer. Specifically, research on patients with liposarcoma, a type of cancer, indicated that some experienced stable disease, meaning it did not worsen. Radiation therapy, which uses high-energy x-rays, is known to help control tumors in specific areas, especially when applied before surgery. Combining abemaciclib with radiation might enhance the tumor-shrinking effect, potentially making surgery more effective for patients with retroperitoneal sarcoma. Early findings suggest this combination could be promising, although further research is needed to confirm its full potential. ^{1 4 5 6 7}

Who Is on the Research Team?

Jeremy Sharib, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults with newly diagnosed or recurrent high-risk adipocytic retroperitoneal sarcoma that can be removed by surgery. Participants must have good liver and kidney function, stable blood counts, no recent major surgeries or serious infections, and not be pregnant or breastfeeding. They should agree to use effective contraception and have a life expectancy of more than 3 months.

Inclusion Criteria

Life expectancy of > 3 months, as determined by the investigator

My kidney function test for protein is normal and I haven't had blood transfusions or certain injections in the last 2 weeks.

My doctors believe my tumor can be removed with surgery.

Exclusion Criteria

My cancer has spread to my brain.

Pregnant or lactating females

I am not taking any medications that can't be stopped or changed and that would interact with abemaciclib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive abemaciclib orally twice daily for up to 3 cycles and undergo radiation therapy over 28 fractions starting on cycle 1 day 15

12 weeks

Multiple visits (in-person) for radiation therapy

Surgery

Participants may undergo surgery after completion of radiation therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Radiation Therapy
• Therapeutic Surgical Procedure

Trial Overview The trial is testing the safety and effectiveness of abemaciclib combined with radiation therapy before surgery in patients with high-risk sarcoma. Abemaciclib is designed to stop tumor growth by blocking certain enzymes needed for cell growth, while radiation aims to kill tumor cells.

How Is the Trial Designed?

Group I: Treatment (abemaciclib, radiation therapy, surgery) Experimental Treatment 5 Interventions

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.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a study of 9068 patients with retroperitoneal sarcoma, both preoperative and postoperative radiotherapy were associated with significantly improved overall survival compared to surgery alone, with median survival times of 110 months and 89 months respectively.

This research is the largest of its kind to date, indicating that radiotherapy can be an effective adjunct to surgical treatment for retroperitoneal sarcoma, supporting its increasing use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: a case-control, propensity score-matched analysis of a nationwide clinical oncology database. Nussbaum, DP., Rushing, CN., Lane, WO., et al.[2022]

Neoadjuvant radiation therapy using a simultaneous integrated boost (SIB) significantly improved abdominopelvic control (96% vs 70%) and recurrence-free survival (60.2% vs 36.3%) in patients with retroperitoneal sarcoma compared to standard techniques, based on a study of 103 patients over a median follow-up of 57 months.

SIB treatment did not increase toxicity and was associated with a lower rate of grade 3 acute toxicity (3% vs 22%), suggesting it is a safer option while providing better disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Simultaneous Integrated Boost Radiation Therapy Improves Clinical Outcomes for Retroperitoneal Sarcoma. Liveringhouse, CL., Palm, RF., Bryant, JM., et al.[2023]

RapidArc radiotherapy for retroperitoneal sarcomas demonstrated effective dosimetric results, with acceptable dose distributions to critical organs in both preoperative and postoperative settings, involving a total of 10 patients.

No severe acute toxicity was observed in the initial treatments, indicating good to excellent tolerability of the RapidArc technique for patients undergoing this type of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of volumetric modulated arc therapy for the treatment of retroperitoneal sarcomas. Llacer-Moscardo, C., Quenet, F., Azria, D., et al.[2021]

In a study of 2,264 patients with nonmetastatic retroperitoneal sarcomas, perioperative radiation therapy was found to significantly reduce mortality, with a hazard ratio of 0.72, indicating a 28% lower risk of death compared to those who did not receive radiation.

Preoperative radiation therapy was associated with a lower rate of positive surgical margins, suggesting it may improve the chances of complete tumor removal, particularly in high-grade tumors and those smaller than 15 cm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Retroperitoneal Sarcomas: Influences of Histology, Grade, and Size. Leiting, JL., Bergquist, JR., Hernandez, MC., et al.[2020]

Extended surgery is the primary treatment for retroperitoneal sarcoma, but there is still uncertainty about the effectiveness of neoadjuvant and adjuvant therapies based on tumor grade and type.

Recent evidence suggests that targeted chemotherapy approaches may be promising, highlighting the importance of centralizing retroperitoneal sarcoma services to support larger international trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma. Almond, LM., Gronchi, A., Strauss, D., et al.[2022]

Intensity modulated radiation therapy (IMRT) significantly improved tumor coverage for retroperitoneal sarcomas, increasing the percentage of the tumor receiving the prescribed dose from 95.3% with 3D-conformal treatment to 98.6% with IMRT.

IMRT also reduced the mean dose to surrounding organs at risk, such as the small bowel, from 36 Gy to 27 Gy, while maintaining effective treatment, suggesting it is a safer and more effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for retroperitoneal sarcoma: a case for dose escalation and organ at risk toxicity reduction. Koshy, M., Landry, JC., Lawson, JD., et al.[2021]

In a study of 2,920 patients with retroperitoneal sarcomas, the overall 5- and 10-year survival rates were found to be 58.4% and 45.3%, respectively, highlighting the serious nature of these tumors.

Patients who underwent surgical resection had a significantly longer survival, living 2.5 times longer, and those who received radiation therapy also experienced improved survival, living 1.3 times longer compared to those who did not receive radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of improved survival for patients with retroperitoneal sarcoma. Giuliano, K., Nagarajan, N., Canner, JK., et al.[2022]

In a study of 1,443 patients with retroperitoneal sarcoma who received both radiation therapy and surgery, the addition of radiation did not improve overall survival, indicating that it may not be beneficial for all patients.

Machine learning analysis identified key prognostic factors such as age, cancer stage, and tumor histology, allowing for the stratification of patients into groups with distinct survival outcomes, suggesting that younger patients with less advanced disease may benefit more from radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors in patients receiving surgery and radiation therapy for retroperitoneal sarcoma: A machine-learning analysis. Zeh, RD., Konieczkowski, D., Shen, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06025747

NCT06025747 | Evaluation of Abemaciclib and Radiation ... Giving abemaciclib together with radiation therapy before surgery may shrink tumors in patients with high-risk adipocytic retroperitoneal sarcoma. Detailed ...

2. targetedonc.com targetedonc.com/view/abemaciclib-demonstrates-promising-clinical-activity-in-dedifferentiated-liposarcoma

Abemaciclib Demonstrates Promising Clinical Activity in ... Abemaciclib is approved by the FDA for the treatment of patients with HR-positive, HER2-negative metastatic breast cancer, and has demonstrated tumor shrinkage ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8820917/

Clinical Utility of CDK4/6 Inhibitors in Sarcoma - PubMed Central Partial response was achieved in three patients (4%), whereas 36 patients achieved stabilized disease (49%). Median PFS ranged from 2.1 to 4.8 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS11587

SARC041: A phase 3 randomized double-blind study of ... We hypothesize that treatment with abemaciclib will improve PFS compared to placebo in patients with recurrent or metastatic DDLS.

5. withpower.com withpower.com/trial/phase-3-liposarcoma-8-2021-3083f

Abemaciclib for Liposarcoma · Info for Participants In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 ...

6. withpower.com withpower.com/trial/phase-1-sarcoma-2024-f648e

Pre-Surgery Abemaciclib + Radiation for Retroperitoneal ... 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 ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.TPS11583

Phase I/II study to evaluate the feasibility and efficacy of ... Sequential administration of abemaciclib followed by gemcitabine enhances apoptosis, impairs DNA repair mechanisms, and induces sustained cell cycle arrest.