Multiple Drug Therapies for Cancer in Children and Young Adults

(CAMPFIRE Trial)

Recruiting at 73 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: < 65

Sex: Any

Trial Phase: Phase 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)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 21-28 days per cycle

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks the best drug combinations for treating various childhood and young adult cancers. It tests drugs like Abemaciclib, a targeted cancer therapy, and Cyclophosphamide, a chemotherapy drug, across multiple study groups. Each group targets specific cancers, such as Ewing's sarcoma and synovial sarcoma. Participants who might be suitable have measurable cancer and have stopped other treatments for at least seven days. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer 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 trial. It does not specify about other medications, so you may need to discuss this with the trial team.

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

Research shows that the safety of treatments in this trial depends on the drug combinations used.

For the combination of Ramucirumab, Cyclophosphamide, and Vinorelbine, studies have found that Ramucirumab is usually well-tolerated in young patients when combined with other chemotherapy drugs. Side effects can occur, but they are often manageable.

In the combination of Ramucirumab, Gemcitabine, and Docetaxel, research indicates that these drugs can be safely used together. However, patients might experience side effects like tiredness and low blood counts, which are common with chemotherapy.

For the combination of Abemaciclib, Irinotecan, and Temozolomide, evidence from previous patients shows that these drugs can be used together safely. Abemaciclib has been tested in other cancers and is generally well-tolerated. Side effects might include diarrhea and nausea, which are typical for these treatments.

These treatments undergo testing to ensure maximum safety, but some side effects are expected with any cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they explore combinations of drugs that target specific features of different sarcomas. Unlike standard chemotherapy, which is often a one-size-fits-all approach, these investigational treatments use targeted therapies like Ramucirumab, which blocks blood vessel growth in tumors, and Abemaciclib, which interferes with cancer cell division. These combinations with drugs like Cyclophosphamide and Vinorelbine for desmoplastic small round cell tumors (DSRCT), and Gemcitabine and Docetaxel for synovial sarcoma (SS), are designed to improve efficacy and reduce side effects by being more precise. Additionally, the use of Abemaciclib with Irinotecan and Temozolomide for Ewing's sarcoma (ES) offers a new angle by combining a cell cycle inhibitor with chemotherapy, potentially enhancing treatment effectiveness.

What evidence suggests that this trial's treatments could be effective for cancer in children and young adults?

In this trial, participants will join different treatment arms to evaluate the effectiveness of various drug combinations for specific cancers in children and young adults. One arm will test the combination of ramucirumab with cyclophosphamide and vinorelbine for desmoplastic small round cell tumors (DSRCT), building on earlier research that found ramucirumab with chemotherapy more effective than chemotherapy alone for certain cancers. Another arm will evaluate ramucirumab with gemcitabine and docetaxel for synovial sarcoma (SS), based on studies that have shown improved outcomes compared to standard chemotherapy. Additionally, the trial will assess the combination of abemaciclib with irinotecan and temozolomide for Ewing's sarcoma (ES), following research that indicated enhanced treatment responses in patients with limited options. These studies suggest that these drug combinations might effectively treat specific cancers in young people. ^{1 2 3 5 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 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 cancer who have a performance score of at least 50, measurable disease, and adequate organ function. They must not have received cancer treatment or investigational agents in the last 7 days. Participants must agree to use effective contraception.

Inclusion Criteria

I agree to use effective birth control during and for 3 months after the trial.

My cancer can be measured or evaluated using standard methods.

My blood counts and organ functions are within normal ranges.

Exclusion Criteria

I have had, or plan to have, a surgery or similar procedure.

Participants who have had allogeneic bone marrow or solid organ transplant

I am currently being treated for an active infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive treatment with various drug combinations in cycles specific to their cancer type

21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment as long as they benefit from it

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Cyclophosphamide
• Docetaxel
• Gemcitabine
• Irinotecan
• Ramucirumab
• Temozolomide
• Vinorelbine

Trial Overview The master protocol oversees multiple trials testing drugs like Cyclophosphamide, Gemcitabine, and others against various cancers in youths. It aims to streamline research by using a common framework that adapts as new treatments are introduced.

How Is the Trial Designed?

Group I: Ramucirumab + Gemcitabine + Docetaxel (SS ISA) Experimental Treatment 3 Interventions

Ramucirumab and gemcitabine given IV in 21-day cycles for synovial sarcoma (SS) ISA.

Group II: Ramucirumab + Cyclophosphamide + Vinorelbine (DSRCT ISA) Experimental Treatment 3 Interventions

Ramucirumab given intravenously (IV), cyclophosphamide given orally and vinorelbine given IV in 28-day cycles for desmoplastic small round cell tumor (DSRCT) intervention-specific appendix (ISA).

Group III: Abemaciclib + Irinotecan + Temozolomide (ES ISA) Experimental Treatment 3 Interventions

Abemaciclib given orally, irinotecan given IV, and temozolomide given orally in 21-day cycles for Ewing's sarcoma (ES) ISA.

Group IV: Cyclophosphamide + Vinorelbine (DSRCT ISA) Active Control 2 Interventions

Cyclophosphamide given orally and vinorelbine given IV in 28-day cycles for DSRCT ISA.

Group V: Gemcitabine + Docetaxel (SS ISA) Active Control 2 Interventions

Gemcitabine and docetaxel given IV in 21-day cycles for SS ISA.

Group VI: Irinotecan + Temozolomide (ES ISA) Active Control 2 Interventions

Irinotecan given IV and temozolomide given orally in 21-day cycles for ES ISA.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast 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

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]

The combination of oral irinotecan, temozolomide, and vincristine was tested in children with relapsed solid tumors, showing that the 5-day treatment schedule (Schedule B) was well tolerated with no dose-limiting toxicities at the highest doses, indicating a safer option for patients.

The study found that this regimen provided similar drug exposure levels to those achieved with intravenous irinotecan, and it demonstrated activity in treating sarcoma, suggesting its potential effectiveness in a range of childhood solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: a Children's Oncology Group phase I consortium study. Wagner, LM., Perentesis, JP., Reid, JM., et al.[2021]

This study assessed the pharmacokinetics of oral vinorelbine in 36 children aged 6 to 18 with recurrent low-grade glioma, revealing that body surface area significantly affects the drug's clearance and distribution.

The findings suggest that children may require higher doses of vinorelbine compared to adults, as they exhibited lower drug exposure levels, indicating a need for further research to optimize treatment in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low-grade glioma. Hamimed, M., Gattacceca, F., André, N., et al.[2022]

The combination of vinorelbine and mitoxantrone showed promising efficacy in treating advanced breast cancer, with response rates of 56% for first-line therapy and 36% for patients resistant to anthracyclines, based on two phase II trials.

A phase I trial indicated that adding prophylactic granulocyte colony-stimulating factors to the vinorelbine and mitoxantrone regimen could be beneficial, but further research is necessary to fully understand the effectiveness and safety of this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with vinorelbine (Navelbine) and mitoxantrone for metastatic breast cancer: a review. Vogel, CL.[2018]

A study involving 36 children with recurrent low-grade glioma revealed that the pharmacokinetics of oral vinorelbine (VNR) can be best described by a three-compartment model, indicating complex absorption and elimination processes.

Factors such as body surface area (BSA), leukocyte count, and the ABCB1-rs2032582 genetic polymorphism significantly influence VNR exposure, suggesting that personalized dosing strategies could enhance treatment efficacy and reduce toxicity in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis. Hamimed, M., Leblond, P., Dumont, A., et al.[2022]

In a study involving 35 children with relapsed or refractory neuroblastoma, the combination of irinotecan, temozolomide, and dinutuximab showed significant anti-tumor activity, with 53% of patients achieving an objective response, including complete responses.

In contrast, the combination of irinotecan, temozolomide, and temsirolimus had a much lower response rate, with only 6% of patients showing a partial response, indicating that the dinutuximab combination is more promising for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Mody, R., Naranjo, A., Van Ryn, C., et al.[2022]

The combination of vincristine, irinotecan, and temozolomide (VIT) was found to be an effective treatment for relapsed or refractory neuroblastoma, achieving an overall objective response rate of 69.6% in a study of 46 patients.

The VIT regimen was well-tolerated, with most toxicities being manageable; while some patients experienced Grade 3-4 hematologic toxicity, the regimen was still considered active and safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma. Zhu, J., Wang, J., Sun, F., et al.[2022]

In a phase II study involving 117 children and young adults with recurrent or refractory solid tumors, the combination of intravenous vinorelbine and oral cyclophosphamide showed a notable response rate of 36% in rhabdomyosarcoma, indicating potential efficacy for this specific cancer type.

The treatment was generally well-tolerated, with neutropenia being the most common severe side effect (38%), while other serious toxicities were rare, suggesting a manageable safety profile that warrants further investigation in larger phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: good tolerance profile and efficacy in rhabdomyosarcoma--a report from the Société Française des Cancers et leucémies de l'Enfant et de l'adolescent (SFCE). Minard-Colin, V., Ichante, JL., Nguyen, L., et al.[2018]

Malignant tumors in young patients are challenging to treat due to their rarity and limited data, highlighting the need for new therapeutic approaches.

Combining chemotherapeutic agents like Vincristine, Temozolomide, and Irinotecan, along with the anti-VEGF drug Bevacizumab, shows promise in enhancing treatment efficacy for pediatric solid tumors, suggesting that the VIT(b) regimen warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of current results with the vincristine-irinotecan-temozolomide combination with or without bevacizumab in pediatric, adolescence and adult solid tumors. Tsakatikas, S., Papageorgiou, G., Fioretzaki, R., et al.[2021]

The addition of bevacizumab to the VOIT regimen (vincristine, oral irinotecan, and temozolomide) in a pediatric trial showed some antitumor activity, particularly in patients with Ewing sarcoma, but the overall benefit of adding bevacizumab is still uncertain.

Reducing the dose of temozolomide from 150 mg/m² to 100 mg/m² improved the tolerability of the treatment, allowing more patients to complete the therapy without significant dose reductions due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors. Wagner, L., Turpin, B., Nagarajan, R., et al.[2020]

Citations

1. 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.

2. 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 ...

3. 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.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6279561/

Abemaciclib is Active in Preclinical Models of Ewing's ... Patients with relapsed or recurrent ES who receive treatment regimens including irinotecan and temozolomide (TMZ) have response rates of up to 68%, with a 1- ...

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.

6. withpower.com withpower.com/trial/phase-2-sarcoma-7-2022-3a19c

Abemaciclib + Chemotherapy for 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 ...