Onivyde + Talazoparib/Temozolomide for Ewing Sarcoma

Not currently recruiting at 11 trial locations
SF
Overseen BySara Federico, MD
Age: < 65
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: St. Jude Children's Research Hospital
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for children and young adults with solid tumors that have returned or not fully responded to previous treatments. It tests two drug combinations: Onivyde (a chemotherapy drug) with talazoparib (a PARP inhibitor), and Onivyde with temozolomide (an oral chemotherapy drug). The goal is to determine the best dose for each combination and assess their effectiveness against the tumors. This study may suit those with a solid tumor that persists or recurs after initial treatment. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific requirements about the time that must pass after certain treatments before joining the study, such as chemotherapy or radiotherapy. It's best to discuss your current medications with the trial team to get a clear answer.

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

Research shows that using Onivyde and talazoparib together aims to damage the DNA of cancer cells and prevent repair. This method remains experimental for children and young adults with solid tumors, as it is being tested for safety and effectiveness. Onivyde is also being tested with temozolomide, which similarly targets cancer cell DNA.

In earlier studies, Onivyde combined with talazoparib or temozolomide aimed to stop or shrink tumors. The safety of these combinations is still under evaluation, especially in young people. So far, no specific safety issues have emerged, but as this is a Phase 1 and Phase 2 trial, the primary goal is to determine the safest dose levels. This indicates the treatment is in early testing stages, and researchers are closely monitoring participants' responses.

While these drugs are being tested in this trial, Onivyde is already used in other adult treatments, suggesting some known safety information. However, its use in children and young adults is still under careful study. Participants in the trial will be closely monitored to ensure the treatment's safety.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to tackling Ewing sarcoma, a rare and aggressive cancer. Unlike the standard chemotherapy options typically used, Onivyde is a nanoliposomal formulation of irinotecan, which allows for better delivery and absorption by the cancer cells, potentially enhancing effectiveness. Additionally, Talazoparib is a PARP inhibitor that disrupts cancer cell DNA repair mechanisms, a novel approach in this context. Meanwhile, Temozolomide, when combined with Onivyde, could enhance the cancer-killing effect due to its ability to damage cancer cell DNA. These innovative combinations aim to improve outcomes for patients with limited options.

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

Research has shown that combining Onivyde and talazoparib, which participants in this trial may receive in Arm A, might help stop or shrink solid tumors, such as Ewing sarcoma. Onivyde damages the DNA of cancer cells, while talazoparib prevents the repair of this damage, potentially leading to cancer cell death. Another approach in this trial, Arm B, uses Onivyde with temozolomide, both of which damage cancer cell DNA and may shrink tumors. These combinations remain experimental for children and young adults with Ewing sarcoma, but early studies have shown promise in other cases. It is important to note that these treatments are being tested to determine the best doses and assess their effectiveness for Ewing sarcoma.12346

Who Is on the Research Team?

Sara Federico, M.D., receives NCI award ...

Sara M Federico, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged between 1 and 30 with recurrent or refractory solid tumors, including Ewing sarcoma. Participants must have measurable disease, be in a certain health condition (Karnofsky >50% or Lansky >50%), have adequate organ function, not be pregnant or breastfeeding, agree to use contraception, and have recovered from previous treatments.

Inclusion Criteria

My cancer can be measured or seen on tests.
My organs and bone marrow are functioning well.
My cancer came back or didn't respond after my first treatment.
See 11 more

Exclusion Criteria

I am using two forms of birth control.
Pregnant or breastfeeding
I am a woman who cannot become pregnant due to surgery.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive Onivyde plus talazoparib or Onivyde plus temozolomide to determine the recommended phase 2 doses (RP2Ds)

Up to 24 months
Intravenous Onivyde on Days 1 and 8, oral talazoparib or temozolomide on specified days

Phase II Treatment

Participants with Ewing sarcoma receive Onivyde plus talazoparib or Onivyde plus temozolomide to evaluate progression-free survival

Up to 24 months
Intravenous Onivyde on Days 1 and 8, oral talazoparib or temozolomide on specified days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Onivyde
  • Talazoparib
  • Temozolomide
Trial Overview The study tests Onivyde combined with either talazoparib or temozolomide in two separate arms (A & B) to find the highest tolerable doses against solid tumors. It includes expansion arms for different tumor types at these doses. Phase II focuses on Ewing sarcoma patients testing the same combinations.
How Is the Trial Designed?
2Treatment groups
Active Control
Group I: (Arm A) ONI plus TALActive Control2 Interventions
Group II: (Arm B) ONI plus TMZActive Control2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials
451
Recruited
5,326,000+

Pfizer

Industry Sponsor

Trials
4,712
Recruited
50,980,000+
Known For
Vaccine Innovations
Top Products
Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni profile image

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Ipsen

Industry Sponsor

Trials
358
Recruited
74,600+
David Loew profile image

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri profile image

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

The protracted d × 5×2 schedule of vincristine, irinotecan, and temozolomide (VIT) demonstrated a significantly higher objective response rate (54.5%) compared to the shorter d × 5 schedule (20.8%) in patients with relapsed or refractory Ewing sarcoma, based on a study of 46 patients.
Patients on the d × 5 schedule experienced more severe adverse events, indicating that the d × 5×2 schedule not only provided better efficacy but also had a more favorable safety profile.
Longer versus Shorter Schedules of Vincristine, Irinotecan, and Temozolomide (VIT) for Relapsed or Refractory Ewing Sarcoma: A Randomized Controlled Phase 2 Trial.Xu, J., Xie, L., Sun, X., et al.[2023]
The nanoparticle formulation of talazoparib (NanoTLZ) significantly reduced toxicity compared to the oral form of talazoparib when combined with temozolomide (TMZ), allowing for a higher maximum tolerated dose.
Using NanoTLZ with TMZ did not require a dose reduction of TMZ, which was necessary when using oral talazoparib, suggesting that this delivery method may enhance the safety and efficacy of the treatment for Ewing sarcoma.
Nanoformulation of Talazoparib Increases Maximum Tolerated Doses in Combination With Temozolomide for Treatment of Ewing Sarcoma.Baldwin, P., Likhotvorik, R., Baig, N., et al.[2020]
In a phase II trial involving 38 patients with recurrent oligodendroglial tumors, temozolomide (TMZ) demonstrated a high response rate, with 52.6% of patients showing a complete or partial response, indicating its efficacy as a first-line chemotherapy.
TMZ was generally well tolerated, with hematologic side effects being the most common, and only one patient discontinuing treatment due to toxicity, suggesting a favorable safety profile for chemotherapy-naive patients.
Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.van den Bent, MJ., Taphoorn, MJ., Brandes, AA., et al.[2022]

Citations

NCT04901702 | Study of Onivyde With Talazoparib or ...To compare the progression-free survival (PFS) of Onivyde plus talazoparib and Onivyde plus temozolomide in patients with refractory or recurrent Ewing sarcoma.
Onivyde in Combination with Talazoparib or ...Giving Onivyde in combination with talazoparib or temozolomide may stop the growth of or shrink solid tumors or Ewing Sarcoma. Eligibility Criteria ...
ONITT: Study of Onivyde with Talazoparib or ...The treatment in this study is considered experimental because it has not been proven to work in children and young adults with solid tumors or Ewing sarcoma.
Study of Onivyde With Talazoparib or Temozolomide in ...To compare the progression-free survival (PFS) of Onivyde plus talazoparib and Onivyde plus temozolomide in patients with refractory or recurrent Ewing sarcoma.
Cancer and Hematology Center Study of Onivyde With ...This is phase I/II study which will evaluate two treatment regimens; nanoliposomal irinotecan (nal-IRN, Onivyde) plus talazoparib (TAL) and Onivyde (ONI) plus ...
Targeting DNA repair pathway in cancer - PubMed Central - NIHIn this review, we sought to summarize the complex network of DNA repair machinery in cancer cells and discuss the underlying mechanism for the application of ...
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