Atezolizumab + Chemotherapy for Pediatric Solid Cancers

Recruiting at 6 trial locations

Overseen By Matthew Campbell, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Matthew Campbell

Must not be taking: Immunosuppressants, CYP3A4 inducers

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs, including atezolizumab (an immunotherapy drug), for children with solid tumors that have returned or resisted treatment. The goal is to assess the safety and effectiveness of this medication mix. Eligible participants must have a relapsed or stubborn solid tumor and have previously tried at least one other treatment. This trial specifically targets those with rhabdomyosarcoma (a type of cancer that forms in soft tissue) and tumors that may express a protein called PD-L1. Participants will receive treatment for up to two years, or until their cancer worsens or they experience serious side effects. As a Phase 1, Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific washout periods for certain treatments, such as chemotherapy, radiotherapy, and some immunosuppressive medications, before starting the study treatment. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

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

Research has shown that combining atezolizumab with vincristine, irinotecan, and temozolomide is generally safe for children with solid tumors. Earlier studies found this combination safe enough to continue testing in children.

Most children in these studies tolerated the treatment well, with serious side effects being uncommon. While side effects can occur, they were not severe enough to halt the study.

Each of these drugs has been used before, either alone or with other drugs, and doctors are familiar with their safety profiles. This includes knowing which side effects to monitor and how to manage them.

Prospective trial participants should discuss possible side effects with the study team. The team can provide detailed information based on the latest research and study findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for pediatric solid cancers, like chemotherapy, attack cancer cells directly but can also harm healthy cells. However, researchers are excited about combining atezolizumab with chemotherapy because it works differently by boosting the immune system to recognize and fight cancer cells more effectively. Atezolizumab is an immune checkpoint inhibitor that targets the PD-L1 protein on tumor cells, making it easier for the immune system to detect and destroy them. This combination could potentially enhance the effectiveness of traditional chemotherapy treatments like irinotecan, temozolomide, and vincristine, offering hope for improved outcomes in tough-to-treat cancers like rhabdomyosarcoma.

What evidence suggests that this trial's treatments could be effective for pediatric solid cancers?

In this trial, participants will receive a combination of atezolizumab with vincristine, irinotecan, and temozolomide. Research has shown that this combination is generally well-tolerated in children with solid tumors. Atezolizumab aids the immune system in fighting cancer by targeting a protein called PD-L1. Studies have found that irinotecan can enhance tumor response to treatment, particularly in cases like rhabdomyosarcoma. Temozolomide has extended survival in children with solid tumors by about 2.5 months. Adding temozolomide to vincristine and irinotecan has also improved tumor response to treatment. This combination treatment shows promise for treating solid tumors in children that have recurred or are not responding to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Arhanti Sadanand, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 6 months to 30 years with relapsed or refractory solid tumors, including rhabdomyosarcoma. Participants must have had at least one prior therapy, meet specific health criteria (like organ function tests), agree to use effective contraception if of childbearing potential, and be able to follow the study protocol.

Inclusion Criteria

My neurological condition has been stable for the last week.

Hemoglobin ≥ 90 g/L (9 g/dL)

Serum albumin ≥ 25 g/L (2.5 g/dL)

Exclusion Criteria

You have a history of severe or uncontrolled asthma.

I am on a stable or reducing dose of steroids for my CNS condition, approved by the study lead.

I've had high-dose chemotherapy and stem-cell therapy within the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Feasibility Cohort Treatment

Participants receive vincristine, irinotecan, temozolomide, and atezolizumab to determine feasibility

Up to 2 years

Regular visits as per protocol

RMS Efficacy Cohort Treatment

Participants with rhabdomyosarcoma receive the combination treatment to evaluate efficacy

Up to 2 years

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 days post treatment

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Irinotecan
• Temozolomide
• Vincristine

Trial Overview The VITAS trial is testing a combination of drugs: vincristine, irinotecan, temozolomide, and atezolizumab in pediatric patients. It's an open-label Phase I/II study which means everyone gets the treatment and both safety and effectiveness are being measured.

How Is the Trial Designed?

Group I: Rhabdomyosarcoma (RMS) Cohort: Patients with rhabdomyosarcoma Experimental Treatment 4 Interventions

Seventeen (17) participants with RMS, including the six participants from the Feasibility Cohort, will be enrolled. At least 8 of the RMS participants must have a tumor that expresses the protein PD-L1. Atezolizumab will be administered in combination with vincristine, irinotecan, and temozolomide for up to 2 years or until the participant experiences disease progression or an unacceptable toxicity.

Group II: Feasibility Cohort: Patients with relapsed or refractory solid tumors Experimental Treatment 4 Interventions

Six (6) participants with relapsed or refractory solid tumor will be enrolled. Atezolizumab will be administered in combination with vincristine, irinotecan, and temozolomide for up to 2 years or until the participant experiences disease progression or an unacceptable toxicity.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Matthew Campbell

Lead Sponsor

Trials

1

Recruited

20+

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

A combination of temozolomide and irinotecan was found to be tolerable and active in treating advanced Ewing sarcoma, with 1 complete response and 3 partial responses observed among 14 evaluable patients.

The treatment regimen was manageable, with minimal myelosuppression and only 11% of courses experiencing grade 3-4 diarrhea, suggesting that home administration of irinotecan is safe and feasible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Wagner, LM., McAllister, N., Goldsby, RE., 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]

In a study of 34 children with heavily pretreated refractory/relapsed solid tumors, the combination of vincristine, irinotecan, and temozolomide showed a 26.4% objective response rate, with particularly promising results in Ewing sarcoma patients (40% response).

The treatment was generally well tolerated, although diarrhea was a common side effect, with 10% of treatment courses resulting in severe cases (grade 3-4).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vincristine, irinotecan, and temozolomide treatment for refractory/relapsed pediatric solid tumors: A single center experience. Büyükkapu Bay, S., Kebudi, R., Görgün, O., et al.[2019]

In a study of 32 pediatric patients with refractory or relapsed solid tumors, the combination of irinotecan and temozolomide resulted in a positive response in 33% of evaluable patients, with 2 achieving complete remission and 8 achieving partial remission.

The treatment was well tolerated, with only 28% of the 180 treatment cycles resulting in toxicity, and severe side effects (grade III-IV) occurring in just 8% of cases, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Irinotecan plus temozolomide in refractory or relapsed pediatric solid tumors]. Hernández-Marqués, C., Lassaletta-Atienza, A., Ruiz Hernández, A., et al.[2018]

In a phase II study involving 66 children with relapsed or refractory medulloblastoma, the combination of temozolomide and irinotecan (TEMIRI) showed an objective response rate of 32.6% after the first 4 treatment cycles, indicating some efficacy in this challenging patient population.

Despite not meeting the primary endpoint for tumor response, TEMIRI was well-tolerated, with manageable side effects, suggesting it could serve as a suitable chemotherapy backbone for future treatments involving targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study. Grill, J., Geoerger, B., Gesner, L., et al.[2021]

A survey of pediatric oncologists revealed that antiemetics are used 17%, 79%, and 98% of the time for chemotherapy agents associated with mild, moderate, and severe nausea and vomiting, respectively, indicating a strong reliance on antiemetic therapy based on the severity of symptoms.

The choice of antiemetics is primarily influenced by oncologists' personal experiences rather than current literature, which suggests that existing practices may not always align with the best available evidence for managing chemotherapy-induced nausea and vomiting in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of antiemetic use in children with cancer. van Hoff, J., Hockenberry-Eaton, MJ., Patterson, K., et al.[2015]

In a study involving 565 pediatric cancer patients undergoing highly emetogenic chemotherapy, palonosetron combined with dexamethasone was found to be highly effective in preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV).

The 10 μg/kg dose of palonosetron demonstrated superior efficacy in the delayed phase of CINV compared to both the 5 μg/kg palonosetron and ondansetron, with complete response rates of 53.5% versus 39.8% and 32.8%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palonosetron is nonsuperior to ondansetron in acute phase but provides superior antiemetic control in delayed phase for pediatric patients administered highly emetogenic chemotherapy. Tan, J., Wang, S., Liang, X., et al.[2018]

In a study of 30 patients with testicular germ cell tumors undergoing 5-day cisplatin chemotherapy, the combination of palonosetron, aprepitant, and dexamethasone achieved a high complete response rate of 90% for preventing vomiting during the first chemotherapy course.

The antiemetic regimen was well-tolerated, with only mild adverse effects reported, such as hiccups and anorexia, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic efficacy and safety of a combination of palonosetron, aprepitant, and dexamethasone in patients with testicular germ cell tumor receiving 5-day cisplatin-based combination chemotherapy. Hamada, S., Hinotsu, S., Kawai, K., et al.[2021]

In a study involving pediatric cancer patients undergoing highly or moderately emetogenic chemotherapy, 20 μg/kg of palonosetron showed higher complete response rates in preventing nausea and vomiting compared to ondansetron.

The safety profile of palonosetron was comparable to that of ondansetron, indicating that it is both an effective and safe option for managing chemotherapy-induced nausea and vomiting over multiple treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study. Kovács, G., Wachtel, A., Basharova, E., et al.[2018]

In a study of 21 patients with high-grade glioma undergoing treatment with temozolomide and radiotherapy, a combination of palonosetron, aprepitant, and dexamethasone effectively managed chemotherapy-induced nausea and vomiting (CINV), achieving a 76.2% complete response rate.

The treatment resulted in very high percentages of patients experiencing no moderate to severe nausea (90.5% in the early phase and 100% in the late phase), and completely eliminated severe appetite suppression, indicating both efficacy and good tolerability of the antiemetic regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Palonosetron, Aprepitant, and Dexamethasone Effectively Controls Chemotherapy-induced Nausea and Vomiting in Patients Treated with Concomitant Temozolomide and Radiotherapy: Results of a Prospective Study. Matsuda, M., Yamamoto, T., Ishikawa, E., et al.[2018]

This phase I study involving 49 patients aimed to identify the maximum tolerated doses and dose-limiting toxicities of irinotecan and temozolomide, revealing significant gastrointestinal toxicities such as diarrhea and neutropenia at certain dose levels.

Two partial responses were observed in patients with glioblastoma and head and neck cancer, indicating some efficacy of the drug combination, although the recommended doses for phase II trials are still being determined due to ongoing patient accrual.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I. Trial of irinotecan and temozolomide in patients with solid tumors. Jones, SF., Gian, VG., Greco, FA., et al.[2018]

Irinotecan (CPT-11) has demonstrated a broad range of antitumor activity across various cancer types, including lymphoma, leukemia, and several solid tumors, although most studies have focused on colorectal and gastrointestinal cancers.

Preliminary results indicate that irinotecan shows modest but reproducible activity in multiple cancers, suggesting the need for further well-designed clinical trials to better understand its efficacy and optimal use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. Rosen, LS.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40937822/

Feasibility of Atezolizumab in Combination With ... Conclusions: Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/pbc.32046?af=R

Feasibility of Atezolizumab in Combination With ... Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors. Efficacy of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04796012

Study Details | NCT04796012 | VITAS: Atezolizumab in ... In this study, we will test the combination of atezolizumab with chemotherapy for relapsed solid tumors in childhood. The combination of vincristine, ...

4. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/VITAS-052124

Clinical Trials / Research Studies ... We will determine the objective response rate, duration of response, and progression-free survival for all children with relapsed or refractory solid tumors ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT189494

A phase I/II study of atezolizumab in pediatric and young ... Background: Atezolizumab targets programmed death-ligand 1 (PD-L1), leading to enhanced anticancer T-cell response. The iMATRIX-Atezolizumab study (phase ...

6. researchgate.net researchgate.net/publication/395456108_Feasibility_of_Atezolizumab_in_Combination_With_Chemotherapy_for_Children_With_Relapsed_or_Refractory_Solid_Tumors

Feasibility of Atezolizumab in Combination With ... Conclusions Atezolizumab combined with vincristine, irinotecan, and temozolomide was feasible and well tolerated in children with solid tumors.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04796012/vitas-atezolizumab-in-combination-with-chemotherapy-for-pediatric-relapsed-refractory-solid-tumors

VITAS: Atezolizumab in Combination With Chemotherapy ... In this study, we will test the combination of atezolizumab with chemotherapy for relapsed solid tumors in childhood. The combination of ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.00124

Randomized Phase II Trial of Vincristine-Irinotecan With or ... The study showed that the addition of the chemotherapy drug temozolomide to vincristine and irinotecan chemotherapy improved tumor response and ...