LY2880070 + Gemcitabine for Ewing Sarcoma

Overseen By Viswatej Avutu, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Anticonvulsants

Disqualifiers: Uncontrolled infection, CNS metastases, 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: Unknown

Duration: 6 months

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a new drug, LY2880070, combined with the chemotherapy drug gemcitabine, can effectively treat Ewing sarcoma or Ewing-like sarcoma. These cancers are tough to treat, and the combination aims to stop cancer cells from growing and dividing more effectively than current treatments. Gemcitabine is an active drug in advanced breast cancer both as a single agent and in combination with other chemotherapeutic agents.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you must have a stable dose of anticonvulsants for CNS disease for at least 4 weeks before enrolling. Additionally, there are specific time requirements for stopping prior cancer therapies: 21 days for cytotoxic chemotherapy, 14 days for radiation, and 21 days for antibody therapy.

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 time requirements for stopping certain cancer treatments before joining the trial, such as a 21-day period after the last dose of chemotherapy.

What data supports the idea that LY2880070 + Gemcitabine for Ewing Sarcoma is an effective drug?

The available research does not provide specific data on the effectiveness of LY2880070 + Gemcitabine for Ewing Sarcoma. Instead, it discusses other treatments like Gemcitabine with Docetaxel and various chemotherapy regimens. Without direct evidence from studies on LY2880070 + Gemcitabine, we cannot conclude its effectiveness for Ewing Sarcoma based on the provided information. ^{1 2 3 4 5}

What data supports the effectiveness of the drug LY2880070 + Gemcitabine for Ewing Sarcoma?

The research highlights the use of Gemcitabine in combination with other drugs like Docetaxel for Ewing Sarcoma, showing it is part of intensive chemotherapy regimens. Although LY2880070 is not directly mentioned, Gemcitabine's inclusion in trials suggests it is considered a viable component in treating this type of cancer. ^{1 2 3 4 5}

What safety data exists for LY2880070 and Gemcitabine in treating Ewing Sarcoma?

The provided research does not directly address the safety data for the combination of LY2880070 and Gemcitabine in treating Ewing Sarcoma. However, Gemcitabine has been studied in combination with other drugs like Docetaxel and nab-paclitaxel for Ewing Sarcoma, indicating its use in treatment regimens. The safety and efficacy of these combinations have been evaluated in various trials, but specific safety data for LY2880070 combined with Gemcitabine is not available in the provided studies. ^{1 4 6 7 8}

What safety data exists for LY2880070 + Gemcitabine in humans?

The safety of Gemcitabine, also known as Gemzar, has been evaluated in combination with other drugs like docetaxel and nab-paclitaxel for treating Ewing sarcoma and other cancers. These studies generally focus on the effectiveness and safety of these combinations, indicating that Gemcitabine is commonly used in cancer treatment regimens. ^{1 4 6 7 8}

Is the drug Gemcitabine, LY2880070 a promising treatment for Ewing Sarcoma?

Gemcitabine, often used in combination with other drugs, has shown promise in treating Ewing Sarcoma, especially in cases where the disease has returned. It is part of ongoing research to find effective treatments for this type of cancer. ^{1 3 4 5 7}

What makes the drug LY2880070 + Gemcitabine unique for treating Ewing Sarcoma?

The combination of LY2880070 and Gemcitabine is unique for Ewing Sarcoma as it explores a novel approach by combining a new investigational drug (LY2880070) with Gemcitabine, which is already used in other sarcoma treatments. This combination may offer a different mechanism of action or improved effectiveness compared to traditional chemotherapy regimens. ^{1 3 4 5 7}

Research Team

Emily Slotkin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals of any age who weigh at least 40 kg and can swallow capsules. They must have Ewing sarcoma or similar, with measurable disease confirmed by specific molecular features. Participants need to be relatively healthy (Karnofsky ≥70% or Lansky ≥70), have adequate organ function, and no more than four prior cancer treatments. Pregnant individuals, those with certain heart conditions, uncontrolled infections, or hypersensitivity to gemcitabine are excluded.

Inclusion Criteria

I've had no more than 4 cancer treatments and have waited the required time after my last treatment.

Organ Function Requirements: Adequate bone marrow function defined as: Absolute neutrophil count (ANC) ≥ 1500/mm3. Platelet count ≥ 100,000/mm3. Hemoglobin ≥ 8 g/dl. Adequate renal function defined as estimated glomerular filtration (eGFR) rate ≥ 60 mL/min/1.73m2: as estimated by CKD-EPI equation for patients ≥ 18 years of age OR As estimated by cystatin C for patients < 18 years of age. Adequate liver function defined as: Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal for age. AST or ALT ≤ 2.5 x upper limit of normal for patients without liver metastases. AST or ALT ≤ 5 x upper limit of normal for patients with liver metastases. Serum albumin ≥ 2.5 g/dl. Adequate cardiac function defined as: Left ventricular ejection fraction (LVEF) >45% as measured on echocardiogram, cardiac MRI, or MUGA. QTc < 470 ms on screening 12 lead electrocardiogram. Pregnancy/Contraception: Post-menarchal females must have a negative urine or serum pregnancy test at screening and ≤ 24 hours prior to study treatment. Males or females of reproductive potential must be willing to use a barrier method of contraception throughout the course of the study and for 6 months after completing study treatment

My cancer did not respond to standard chemotherapy treatments.

Exclusion Criteria

Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

I have a history of heart issues including Torsades de Pointes, congestive heart failure, or a family history of prolonged QT syndrome.

Patients who are pregnant or breast feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY2880070 combined with the chemotherapy drug gemcitabine

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gemcitabine
• LY2880070

Trial Overview The study tests the effectiveness of LY2880070 combined with chemotherapy drug gemcitabine in treating advanced Ewing sarcoma and related diseases. It aims to determine if this combination therapy can provide a new treatment option for patients who have not responded well to standard therapies.

Participant Groups

Group I: Ewing sarcoma Experimental Treatment 2 Interventions

Participants have a diagnosis of Ewing sarcoma as molecularly defined by an EWSR1 fusion with an ETS-transcription factor family member including FLI1, ERG, ETV1, ETV4, and FEV

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

In a study of 43 patients with newly diagnosed high-risk Ewing sarcoma, the combination of Gemcitabine and Docetaxel (G/D) showed a 70.6% objective response rate during the initial treatment phase, indicating its potential efficacy in this patient group.

The 5-year overall survival rate was significantly higher for patients under 18 years old (74.0%) compared to those over 18 (31.0%), suggesting that age at diagnosis is a critical prognostic factor in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS). Mora, J., Castañeda, A., Perez-Jaume, S., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a study of 235 adolescent-adult patients with nonmetastatic Ewing sarcoma treated with the EFT-2001 chemotherapy regimen, the estimated 3-year event-free survival (EFS) was 67.3% and overall survival (OS) was 91.1%, indicating effective treatment outcomes.

The treatment was associated with manageable toxicities, with significant grade 3-4 side effects including febrile neutropenia (50.6%) and anemia (55.3%), suggesting that while the regimen is effective, it does carry risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country. Bajpai, J., Panda, GS., Chandrasekharan, A., et al.[2022]

The study evaluated the safety and dosing of the PARP inhibitor niraparib combined with temozolomide or irinotecan in 29 patients with pretreated Ewing sarcoma, identifying a maximum tolerated dose for both combinations.

While the treatment was tolerable, it resulted in a median progression-free survival of 9.0 weeks for the niraparib and temozolomide group and 16.3 weeks for the niraparib and irinotecan group, indicating potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma. Chugh, R., Ballman, KV., Helman, LJ., et al.[2021]

Recent clinical trials have established interval-compressed chemotherapy as the international standard treatment for newly diagnosed localized Ewing sarcoma, improving treatment protocols for patients.

High-dose chemotherapy and IGF-1R inhibition have shown no significant benefit for patients with newly diagnosed metastatic Ewing sarcoma, indicating the need for continued research into more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ewing Sarcoma Drug Therapy: Current Standard of Care and Emerging Agents. Setty, BA., Gikandi, A., DuBois, SG.[2023]

In a study of 10 pediatric patients with relapsed or refractory sarcomas, the combination of gemcitabine and docetaxel showed significant antitumor activity, with 50% of patients achieving a complete or partial response.

The treatment was well-tolerated, with only mild toxicities reported, and allowed for a median duration of response of 10 months, indicating a good quality of life for the patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. Mora, J., Cruz, CO., Parareda, A., et al.[2022]

In a phase II trial involving 11 heavily pretreated patients with relapsed Ewing sarcoma, the combination of gemcitabine and nab-paclitaxel resulted in a confirmed response rate of only 9%, indicating limited efficacy for this treatment in this patient population.

The treatment was associated with significant toxicity, particularly myelosuppression, leading to the removal of 36% of patients due to hematologic issues, despite supportive measures like pegfilgrastim.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation. Oesterheld, JE., Reed, DR., Setty, BA., et al.[2022]

The combination of metformin and imatinib has been shown to enhance the anti-tumor effects against Ewing sarcoma (EwS) by reducing the tumor's hypoxic response, which is a major barrier to metformin's efficacy.

This drug combination not only targets key pathways involved in EwS growth and metastasis but also improves the effectiveness of standard chemotherapy drugs, suggesting it could allow for lower doses of chemotherapy while maintaining survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways. Nan, X., Wang, J., Cheng, H., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS). [2023]

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

Longer versus Shorter Schedules of Vincristine, Irinotecan, and Temozolomide (VIT) for Relapsed or Refractory Ewing Sarcoma: A Randomized Controlled Phase 2 Trial. [2023]

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

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country. [2022]

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

SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Ewing Sarcoma Drug Therapy: Current Standard of Care and Emerging Agents. [2023]

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

Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel. [2022]

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

Phase II trial of gemcitabine and nab-paclitaxel in patients with recurrent Ewing sarcoma: A report from the National Pediatric Cancer Foundation. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways. [2021]