45 Participants Needed

Abemaciclib + Chemotherapy for Sarcoma

Recruiting at 30 trial locations
Tm
Overseen ByThere may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding a new drug called abemaciclib to standard cancer treatments can help children and young adults with Ewing's sarcoma that has come back or did not respond to previous treatments. Abemaciclib works by blocking proteins that help cancer cells grow, which may slow down or stop the tumor. Participation could last several months or more, depending on individual responses.

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.

What data supports the idea that Abemaciclib + Chemotherapy for Sarcoma is an effective drug?

The available research shows that the combination of temozolomide and irinotecan, which are part of the chemotherapy regimen, has been effective in treating certain types of tumors. For example, in studies involving different types of cancer, this combination led to complete responses in several cases, meaning the tumors were no longer detectable. This suggests that the combination can be more effective than using either drug alone. Although the studies primarily focus on other cancers like glioma, the positive results indicate potential effectiveness for sarcoma as well.12345

What data supports the effectiveness of the drug combination of Abemaciclib, Irinotecan, and Temozolomide for treating sarcoma?

Research shows that the combination of Temozolomide and Irinotecan has been effective in treating various tumors, including neuroblastomas and glioblastomas, with better results than using either drug alone. This suggests potential effectiveness for other cancers, like sarcoma, when used in combination.12345

What safety data is available for the combination of Abemaciclib, Irinotecan, and Temozolomide in treating sarcoma?

The safety data for the combination of Irinotecan (CPT-11, Camptosar) and Temozolomide (Temodar) has been evaluated in several studies. In a Phase I trial, dose-limiting toxicities such as diarrhea, neutropenia, and thrombocytopenia were observed at certain doses. Another study reported dose-limiting grade 3 diarrhea, nausea, and vomiting, making some dosing regimens intolerable. The maximum tolerated dose and dose-limiting toxicity were also assessed in patients with recurrent malignant glioma. These studies indicate significant gastrointestinal toxicities and the need for careful dose management. However, specific safety data for the combination with Abemaciclib is not detailed in the provided research.34567

Is the combination of Abemaciclib, Irinotecan, and Temozolomide safe for humans?

The combination of Irinotecan and Temozolomide has been studied in humans, and some patients experienced side effects like diarrhea, low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia). These side effects were dose-limiting, meaning they were severe enough to prevent increasing the dose further.34567

Is the drug combination of Irinotecan and Temozolomide promising for treating sarcoma?

Yes, the combination of Irinotecan and Temozolomide is promising for treating sarcoma, especially Ewing sarcoma. Studies show that this drug combination works well together and has been effective in patients, particularly in children with relapsed solid tumors. It has also been used widely in treating relapsed Ewing sarcoma.2891011

What makes the drug combination of Abemaciclib, Irinotecan, and Temozolomide unique for treating sarcoma?

This drug combination is unique because it uses Abemaciclib, a targeted therapy, alongside Irinotecan and Temozolomide, which have shown synergy (working better together) in treating relapsed Ewing sarcoma, a type of cancer. Temozolomide can cross the blood-brain barrier and has a good safety profile, making it effective in combination therapies.2891011

Research Team

C1

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

Eligibility Criteria

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
See 9 more

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.
See 6 more

Timeline

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

Treatment Details

Interventions

  • Abemaciclib
  • Irinotecan
  • Temozolomide
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Irinotecan +TemozolomideExperimental Treatment2 Interventions
Irinotecan given IV and temozolomide orally.
Group II: Abemaciclib + Irinotecan +TemozolomideExperimental Treatment3 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials
2,708
Recruited
3,720,000+
Dr. Daniel Skovronsky profile image

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks profile image

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

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.
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]
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.
Temozolomide in combination with other cytotoxic agents.Prados, M.[2019]
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.
The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors.Friedman, HS., Keir, ST., Houghton, PJ.[2018]

References

Antitumor activity of temozolomide combined with irinotecan is partly independent of O6-methylguanine-DNA methyltransferase and mismatch repair phenotypes in xenograft models. [2022]
Temozolomide in combination with other cytotoxic agents. [2019]
The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. [2018]
Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. [2021]
Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. [2018]
Irinotecan therapy in adults with recurrent or progressive malignant glioma. [2022]
Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma. [2022]
Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. [2018]
Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma. [2021]
[Chemotherapy of sarcomas: optimization of existing drugs and new molecules]. [2006]
11.United Statespubmed.ncbi.nlm.nih.gov
Sarcoma chemotherapy. [2013]