Multiple Drug Therapies for Cancer in Children and Young Adults

(CAMPFIRE Trial)

Recruiting at 65 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 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

Trial Summary

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.

What data supports the effectiveness of the drug combination used in the clinical trial for cancer in children and young adults?

Research shows that the combination of vinorelbine and cyclophosphamide has been effective in treating relapsed or refractory solid tumors in children and young adults, with good tolerance and efficacy in rhabdomyosarcoma. Additionally, the combination of vincristine, irinotecan, and temozolomide has been effective for relapsed and refractory neuroblastoma, suggesting potential benefits of these drugs in pediatric cancers. ^{1 2 3 4 5}

Is the combination of vinorelbine and cyclophosphamide safe for children and young adults?

The combination of vinorelbine and cyclophosphamide has been studied in children and young adults with relapsed or refractory solid tumors, showing a good tolerance profile, meaning it was generally safe for use in this group. ^{3 4 6 7 8}

What makes the drug combination of Abemaciclib, Cyclophosphamide, Docetaxel, Gemcitabine, Irinotecan, Ramucirumab, Temozolomide, and Vinorelbine unique for treating cancer in children and young adults?

This drug combination is unique because it combines multiple agents that have shown effectiveness in treating various solid tumors in children and young adults, potentially offering a synergistic effect. The inclusion of drugs like Abemaciclib, which targets specific cancer cell growth pathways, alongside traditional chemotherapy agents, aims to enhance treatment efficacy and overcome resistance seen in relapsed or refractory cases. ^{3 5 7 9 10}

What is the purpose of this trial?

This trial tests new cancer drugs to see if they help patients and how long the benefits last. It focuses on different types of cancer and adds new studies as new drugs are developed.

Research Team

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 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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma. [2022]

3. England 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). [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Impact of pharmacogenetics on variability in exposure to oral vinorelbine among pediatric patients: a model-based population pharmacokinetic analysis. [2022]

5. Netherlands 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of oral vinorelbine in French children with recurrent or progressive primary low-grade glioma. [2022]

7. United States 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. [2020]

8. United States 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. [2018]

9. England 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. [2022]

10. United States 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. [2021]