Ramucirumab for Desmoplastic Small Round Cell Tumor

Not currently recruiting at 95 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 1 & 2

Sponsor: Eli Lilly and Company

Disqualifiers: Severe disease, Active infections, Transplant, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for desmoplastic small round cell tumor (DSRCT), a rare cancer affecting children and young adults. The main goal is to determine if adding ramucirumab, a targeted therapy, to the usual chemotherapy drugs, cyclophosphamide and vinorelbine, is safe and effective for tumors that have recurred, not responded to treatment, or worsened despite treatment. The study seeks participants with DSRCT who have undergone at least one prior treatment, have measurable disease, and cannot undergo surgery to remove the tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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 treatment. However, it does not specify if you need to stop other non-cancer medications, so it's best to discuss your current medications with the trial team.

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

Earlier studies have tested ramucirumab for its safety in treating various cancers. Research shows that most people tolerate it well, though some side effects can occur. Common side effects include high blood pressure, diarrhea, and tiredness, while more serious side effects are less frequent.

The other drugs in this trial, cyclophosphamide and vinorelbine, are also generally well-tolerated in cancer treatments. Cyclophosphamide may cause nausea, hair loss, and low blood cell counts. Vinorelbine can lead to tiredness and low blood counts.

This trial focuses on both safety and effectiveness, indicating some existing evidence suggests the treatment might be safe, but more information is needed. Participation in the trial will help gather more data on its safety for treating desmoplastic small round cell tumor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce ramucirumab as a fresh player in the fight against desmoplastic small round cell tumor (DSRCT). Unlike traditional chemotherapy options, ramucirumab is an antibody that targets the blood vessels feeding the tumor, potentially starving it of nutrients needed for growth. This mechanism is different from standard treatments, which usually involve directly attacking cancer cells. The combination of ramucirumab with cyclophosphamide and vinorelbine could offer a more comprehensive approach by both cutting off the tumor's blood supply and attacking the cancer cells directly. This dual-action strategy could lead to better outcomes for patients dealing with this challenging condition.

What evidence suggests that this trial's treatments could be effective for desmoplastic small round cell tumor?

Research has shown that ramucirumab, when combined with chemotherapy, might help treat desmoplastic small round cell tumor (DSRCT). In this trial, one group of participants will receive ramucirumab, cyclophosphamide, and vinorelbine. A study with DSRCT patients found that 16 out of 22 patients had stable disease after 12 weeks, with an average survival of about 15.7 months. This suggests that ramucirumab could help control tumor growth. Another group in this trial will receive cyclophosphamide and vinorelbine without ramucirumab. While these findings are promising, more research is needed to fully understand its benefits. ^{1 4 5 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM 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 children and young adults with relapsed, recurrent, or refractory Desmoplastic Small Round Cell Tumor (DSRCT). Participants must have tried at least one systemic treatment before, not be eligible for surgery, and have adequate organ function. They should not have severe infections, recent significant bleeding events or thrombosis, uncontrolled hypertension, certain heart conditions or a history of severe liver disease.

Inclusion Criteria

I cannot have surgery for my condition right now.

My DSRCT cancer has come back or hasn't responded to treatment.

I have had at least one treatment for my condition before, including chemotherapy.

Exclusion Criteria

Participants with severe and/or uncontrolled concurrent medical disease or psychiatric illness/social situation that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.

I have a history of serious heart, blood vessel problems, or severe reactions to medications.

I have not had significant bleeding or bleeding disorders in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ramucirumab in combination with other chemotherapy drugs, including cyclophosphamide and vinorelbine, for up to 10 cycles of 28 days each

10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if beneficial

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Ramucirumab
• Vinorelbine

Trial Overview

The study tests the safety and effectiveness of Ramucirumab combined with chemotherapy drugs Cyclophosphamide and Vinorelbine in treating DSRCT. It's part of a larger protocol aiming to speed up new cancer treatments for young patients. The commitment could exceed 12 months based on individual response to treatment.

How Is the Trial Designed?

Group I: Ramucirumab + Cyclophosphamide + Vinorelbine Experimental Treatment 3 Interventions

Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Ramucirumab administered intravenously at a dose of 12 milligrams per kilogram (mg/kg) as a one-hour infusion on days 1 and 15. * Cyclophosphamide administered orally at 25 milligrams per meter square (mg/m2) daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.

Group II: Cyclophosphamide + Vinorelbine Active Control 2 Interventions

Participants received the following treatments in a 28-day cycle, continuing until disease progression or a criterion for discontinuation was met. * Cyclophosphamide administered orally at 25 mg/m² daily from days 1 to 28. * Vinorelbine administered intravenously at 25 mg/m² on days 1, 8, and 15.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

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

Vinorelbine (VRL) as second-line chemotherapy for hormone-refractory prostate cancer (HRPC) showed moderate efficacy, with 17.9% of patients experiencing significant declines in prostate-specific antigen levels, indicating a response to treatment.

Patients receiving VRL in combination with estramustine had a median overall survival of 8.5 months, compared to 4.1 months for those on VRL alone, suggesting that the combination therapy may enhance survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to vinorelbine with or without estramustine as second-line chemotherapy in patients with hormone-refractory prostate cancer. Nakabayashi, M., Ling, J., Xie, W., et al.[2018]

Vinorelbine, an oral and intravenous chemotherapy drug, was found to have a maximum tolerated dose of 30 mg/m² in children without bone marrow involvement, with myelosuppression (reduced blood cell production) being the main side effect.

The study revealed that children metabolize vinorelbine differently than adults, showing higher plasma clearance and lower overall drug exposure, which may influence dosing strategies for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group. Johansen, M., Kuttesch, J., Bleyer, WA., et al.[2018]

Vinorelbine tartrate is an effective treatment for non-small cell lung cancer (NSCLC) and has a low reported prevalence of respiratory adverse effects, typically under 5%.

However, there is a potential risk of increased pulmonary toxicity in patients with diffuse pulmonary NSCLC, as demonstrated by a case of acute respiratory failure following vinorelbine infusion in a patient with a hypercoagulable state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory failure following vinorelbine tartrate infusion in a patient with non-small cell lung cancer. Kouroukis, C., Hings, I.[2019]

Vinorelbine tartrate is an FDA-approved treatment for advanced, unresectable non-small cell lung cancer, known for its favorable safety profile and the ability to be administered weekly in an outpatient setting.

While approximately 40% of patients experience severe granulocytopenia, this side effect is quickly reversible, and only about 8% of patients need hospitalization for related complications, indicating that it can be managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate: a promising new chemotherapeutic agent. Baldwin, PD.[2018]

Citations

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In the largest study with DSRCT patients (n = 22) 16 patients had stable disease at 12 weeks of follow up with a median survival of 15.7 months, ...

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This study is being conducted to test the safety and efficacy of ramucirumab in combination with other chemotherapy in the treatment of relapsed, recurrent, ...

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This study is being conducted to test the safety and efficacy of ramucirumab in combination with other chemotherapy in the treatment of relapsed, recurrent, or ...

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Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal ...

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ramucirumab WR

Despite multimodal treatment, including aggressive surgical excision, chemotherapy, and radiotherapy,. DSRCT has only a 15% overall survival ...