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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment involving radiation therapy for retroperitoneal sarcoma?

Research shows that using radiation therapy before surgery for retroperitoneal sarcoma can lower the chance of the cancer coming back and improve survival rates, especially for certain types of tumors. This approach helps target the tumor more precisely while protecting nearby organs. ^{1 2 3 4 5}

Is the combination of Abemaciclib and radiation therapy generally safe for humans?

The research articles provided do not contain specific safety data for the combination of Abemaciclib and radiation therapy. However, they discuss the use of radiation therapy in retroperitoneal sarcoma, focusing on minimizing harm to nearby organs and improving treatment outcomes. ^{1 2 4 6 7}

How is the drug Abemaciclib unique in treating retroperitoneal sarcoma?

Abemaciclib is unique in treating retroperitoneal sarcoma because it is a targeted therapy that inhibits specific proteins (CDK4 and CDK6) involved in cell division, potentially enhancing the effects of radiation therapy by making cancer cells more sensitive to it. This combination approach is novel compared to traditional treatments that primarily focus on surgery and radiation alone. ^{1 4 5 6 8}

Research Team

Elizabeth Loggers, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Radiation Therapy for Retroperitoneal Sarcomas: Influences of Histology, Grade, and Size. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Simultaneous Integrated Boost Radiation Therapy Improves Clinical Outcomes for Retroperitoneal Sarcoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Prognostic factors in patients receiving surgery and radiation therapy for retroperitoneal sarcoma: A machine-learning analysis. [2023]

4. Egypt pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy for retroperitoneal sarcoma: a case for dose escalation and organ at risk toxicity reduction. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant and adjuvant strategies in retroperitoneal sarcoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Feasibility study of volumetric modulated arc therapy for the treatment of retroperitoneal sarcomas. [2021]

7. England 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Predictors of improved survival for patients with retroperitoneal sarcoma. [2022]