Abemaciclib + Chemotherapy for Sarcoma

Not currently recruiting at 35 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must not be taking: CDK 4/6 inhibitors

Disqualifiers: Uncontrolled disease, Active infection, Transplant, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 11 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding abemaciclib, a cancer treatment drug, to chemotherapy with irinotecan and temozolomide can help treat Ewing's sarcoma, a type of cancer that has returned or hasn't responded to previous treatments. Participants will receive either chemotherapy alone or chemotherapy plus abemaciclib. This study is part of a larger effort to develop new cancer treatments for children and young adults. Individuals with Ewing's sarcoma that hasn't responded to treatment and who can handle everyday activities might be a good fit. As a Phase 2 trial, this research focuses on measuring how well the treatment works in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires participants to stop all previous cancer treatments or investigational agents at least 7 days before starting the trial. The protocol does not specify about other medications, but you should discuss with the trial team to understand if you need to stop any other medications.

Will I have to stop taking my current medications?

The trial requires participants to stop all previous cancer treatments or investigational agents at least 7 days before starting the study. It does not specify about other medications, so you may need to discuss your current medications with the trial team.

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

Studies have shown that using irinotecan and temozolomide together is generally safe for patients. These drugs, already used to treat some types of cancer, have a known safety record. Common side effects include nausea, vomiting, and diarrhea, but these are usually manageable.

Research is still investigating the addition of abemaciclib to this treatment. Early results suggest that abemaciclib might cause side effects like tiredness and diarrhea. However, no serious or unexpected safety problems have emerged so far. As this trial is in an early stage, researchers continue to carefully monitor the safety of this new combination for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine abemaciclib with irinotecan and temozolomide, offering a fresh approach for tackling sarcoma. Unlike standard chemotherapy options that mainly focus on killing rapidly dividing cells, abemaciclib is a CDK4/6 inhibitor, which targets specific proteins involved in cell division, potentially slowing down tumor growth in a more targeted manner. By combining this with the known cancer-fighting abilities of irinotecan and temozolomide, there's hope for enhanced effectiveness and improved outcomes for patients who might not respond as well to existing treatments.

What evidence suggests that this trial's treatments could be effective for Ewing's sarcoma?

Research has shown that combining irinotecan and temozolomide, one of the treatment arms in this trial, may benefit patients with relapsed Ewing's sarcoma. Studies have found that this treatment can shrink or control tumors. On average, patients live between 3.8 to 8.3 months without disease progression. Another treatment arm in this trial adds abemaciclib to irinotecan and temozolomide, which might enhance these results. Early findings suggest that abemaciclib could help stop tumor growth when used with irinotecan and temozolomide. While more research is needed, this combination is under study for its potential to improve outcomes in Ewing’s sarcoma. ^{1 2 3 4 5}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for individuals with Ewing's Sarcoma that has returned or didn't respond to treatment. They must have a measurable tumor, weigh at least 10 kg, and have adequate organ function. Participants need to be off previous cancer treatments for at least 7 days and recovered from their effects. Pregnant or breastfeeding women can't join, nor can those who've had certain surgeries recently or are dealing with severe infections like HIV.

Inclusion Criteria

My steroid dose has been stable or decreasing for the last week.

My doctor expects me to live at least 8 more weeks and I can complete a treatment cycle.

Adequate hematologic and organ function ≤14 days prior to Day 1 of Cycle 1: Absolute neutrophil count ≥1000/µL, Platelets ≥75,000/mm³, Hemoglobin ≥8 g/dL, Total bilirubin ≤1.5 × ULN, AST and ALT ≤3 × ULN, Creatinine clearance or calculated GFR ≥60 mL/min/m² or serum creatinine based on age/gender, Female participants of childbearing potential must have a negative urine or serum pregnancy test, Body weight ≥10 kg

Exclusion Criteria

Have a known intolerability or hypersensitivity to any of the study treatments or dacarbazine

I am not pregnant or breastfeeding.

My condition worsened despite previous treatments with irinotecan or temozolomide.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib in combination with irinotecan and temozolomide for Ewing's sarcoma

11 months

Day 1 of Cycles 1 through 3 (21 day cycles)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Irinotecan
• Temozolomide

Trial Overview The study tests the effectiveness of adding abemaciclib to chemotherapy drugs irinotecan and temozolomide in treating Ewing's Sarcoma. It's part of a larger effort called CAMPFIRE designed to accelerate new cancer treatments for young people.

How Is the Trial Designed?

Group I: Irinotecan +Temozolomide Experimental Treatment 2 Interventions

Irinotecan given IV and temozolomide orally.

Group II: Abemaciclib + Irinotecan +Temozolomide Experimental Treatment 3 Interventions

Abemaciclib given orally in combination with irinotecan given IV and temozolomide given orally.

Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Camptosar for:

• Colorectal cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead 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

Irinotecan, a derivative of camptothecin, has shown significant activity against recurrent malignant glioma in clinical trials, confirming its potential as a treatment option for this aggressive brain tumor.

Combining irinotecan with alkylating agents like BCNU or temozolomide enhances its antitumor effects, leading to ongoing Phase II trials to evaluate these combinations in adults with malignant glioma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Friedman, HS., Keir, ST., Houghton, PJ.[2018]

Temozolomide is a promising drug for combination therapies due to its ability to cross the blood-brain barrier, good safety profile, and effectiveness against solid tumors like malignant glioma, especially when combined with carmustine or irinotecan.

Studies indicate that administering carmustine before temozolomide results in lower toxicity and a higher maximum tolerated dose, while the combination of temozolomide followed by irinotecan shows greater effectiveness than either drug alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in combination with other cytotoxic agents. Prados, M.[2019]

In a phase 1 clinical trial involving 55 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of irinotecan (CPT-11) was found to be 120 mg/m² when combined with temozolomide (TMZ) and O(6)-benzylguanine (O(6)-BG) in patients using enzyme-inducing antiepileptic drugs (EIAEDs).

The study identified significant hematologic toxicities, such as grade 4 neutropenia and thrombocytopenia, as dose-limiting factors, highlighting the need for careful monitoring in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Quinn, JA., Jiang, SX., Reardon, DA., et al.[2021]

Irinotecan (CPT-11) demonstrated activity in treating recurrent malignant gliomas, with 15% of patients showing a confirmed partial response and 55% achieving stable disease for over 12 weeks, based on a study of 60 patients.

The treatment was associated with limited toxicity, primarily mild side effects like neutropenia and nausea, but the low plasma concentrations of the drug suggest that concurrent use of anticonvulsants and dexamethasone may reduce its effectiveness by enhancing drug clearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan therapy in adults with recurrent or progressive malignant glioma. Friedman, HS., Petros, WP., Friedman, AH., et al.[2022]

Chemotherapy has become a crucial treatment for sarcomas, significantly improving patient survivorship, with various agents like doxorubicin and cyclophosphamide used in combination to target these tumors.

The effectiveness of chemotherapy is closely linked to the degree of tumor necrosis achieved, but patients often experience a range of side effects, from mild to severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarcoma chemotherapy. Walczak, BE., Irwin, RB.[2013]

In a study involving 107 patients with recurrent malignant glioma, the maximum tolerated dose (MTD) of irinotecan (CPT-11) was found to be 325 mg/m² for those taking enzyme-inducing anticonvulsants and 125 mg/m² for those not taking them, indicating significant variability in tolerance based on concurrent medications.

The combination of CPT-11 and temozolomide (TMZ) resulted in a 14% radiographic response rate, with patients showing a median time to disease progression of 54.9 weeks, suggesting that this treatment regimen may be effective for recurrent glioblastoma multiforme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. Reardon, DA., Quinn, JA., Rich, JN., et al.[2022]

This phase I study involving 49 patients aimed to identify the maximum tolerated doses and dose-limiting toxicities of irinotecan and temozolomide, revealing significant gastrointestinal toxicities such as diarrhea and neutropenia at certain dose levels.

Two partial responses were observed in patients with glioblastoma and head and neck cancer, indicating some efficacy of the drug combination, although the recommended doses for phase II trials are still being determined due to ongoing patient accrual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. Jones, SF., Gian, VG., Greco, FA., et al.[2018]

The combination of temozolomide and irinotecan (CPT-11) was effective in inducing complete responses in various tumors, including four neuroblastomas, two rhabdomyosarcomas, and one glioblastoma, demonstrating greater efficacy than either drug alone.

Interestingly, the synergistic effect of the two drugs was independent of tumor characteristics like MGMT or mismatch repair phenotype, and coadministration of CPT-11 reduced the toxicity of temozolomide, suggesting a safer treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. Houghton, PJ., Stewart, CF., Cheshire, PJ., et al.[2022]

A combination of temozolomide and irinotecan was found to be tolerable and active in treating advanced Ewing sarcoma, with 1 complete response and 3 partial responses observed among 14 evaluable patients.

The treatment regimen was manageable, with minimal myelosuppression and only 11% of courses experiencing grade 3-4 diarrhea, suggesting that home administration of irinotecan is safe and feasible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Wagner, LM., McAllister, N., Goldsby, RE., et al.[2018]

Irinotecan and temozolomide (IT) chemotherapy is effective for treating relapsed Ewing sarcoma, showing similar objective response rates (28% in both pediatric and adult patients) and manageable toxicity levels across age groups.

However, pediatric patients experienced significantly longer progression-free survival (7.4 months) compared to adults (2.2 months), suggesting that age may influence treatment outcomes and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma. Salah, S., To, YH., Khozouz, O., et al.[2021]

Doxorubicin and ifosfamide are the primary chemotherapy drugs used for treating sarcomas, while dacarbazine has limited effectiveness, highlighting the need for improved drug combinations.

New chemotherapy agents like gemcitabine and ET-743 have shown promise in certain sarcoma sub-types, and targeted therapies along with antiangiogenic treatments are beginning to demonstrate positive results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of sarcomas: optimization of existing drugs and new molecules]. Fayette, J., Blay, JY.[2006]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05440786?term=AREA%5BExpandedAccessNCTId%5DNCT03763604&rank=3

NCT05440786 | CAMPFIRE: A Study of Abemaciclib ... The purpose of this study is to measure the benefit of adding abemaciclib to chemotherapy (irinotecan and temozolamide) for Ewing's sarcoma that has come ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12420305/

Case Report: Relapsed alveolar rhabdomyosarcoma treated ... ... abemaciclib in combination with temozolomide and irinotecan may abrogate tumor growth and improve outcomes. However, this evaluation is ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS11580

A randomized, open-label, phase 2 study evaluating ... This study, NCT05440786, will evaluate the potential benefit of adding abemaciclib to irinotecan plus temozolomide for the treatment of relapsed/refractory ES.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-of-abemaciclib-irinotecan-and-temozolomide-for-patients-with-relapsed-or-refractory-ewings-sarcoma/

Study of Abemaciclib, Irinotecan, and Temozolomide for ... Upon completion, the data collected will be analyzed to determine the effectiveness of the treatment combination in managing Ewing's sarcoma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.