Cabozantinib for Rare Cancers in Young Patients

Not currently recruiting at 162 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, Anticoagulants

Disqualifiers: Pregnancy, Uncontrolled infection, Active bleeding, 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: 30

Duration: Up to 6 cycles (24 weeks)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests cabozantinib-s-malate, a treatment that may prevent the growth of certain rare tumors in young patients. It focuses on tumors that have returned, do not respond to other treatments, or are newly diagnosed, such as certain types of sarcomas, Wilms tumor, and other uncommon cancers. The goal is to determine if this medication can block enzymes that aid tumor growth. Suitable candidates have a diagnosed tumor from the list mentioned, such as Ewing sarcoma or Wilms tumor, and have experienced their disease returning or not responding to previous treatments. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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, you cannot participate if you are taking certain medications like potent CYP3A4 inducers or inhibitors, or if you are on certain anticoagulants. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that cabozantinib-s-malate is likely to be safe for young patients?

Research has shown that cabozantinib-s-malate has been tested for safety in younger patients with rare tumors. In one study, children and young adults with various rare tumors received cabozantinib-s-malate. Some patients experienced side effects such as tiredness, high blood pressure, and diarrhea, but these were usually manageable. The treatment has been used previously for other conditions, providing some confidence in its safety. As this trial is in an early phase, researchers continue to closely monitor for any possible side effects. However, past experiences suggest it is generally well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cabozantinib-s-malate is unique because it targets specific pathways involved in the growth and spread of cancer cells, which is different from most standard treatments for rare cancers in young patients that often rely on chemotherapy or radiation. This drug is taken orally, making it more convenient compared to treatments that require hospital visits for administration. Researchers are excited about cabozantinib-s-malate because it has shown promise in inhibiting tumor growth by blocking multiple tyrosine kinases, potentially offering a more targeted approach with fewer side effects than traditional therapies.

What evidence suggests that cabozantinib-s-malate might be an effective treatment for rare cancers in young patients?

Research has shown that cabozantinib-s-malate can help treat some rare cancers. In earlier studies, some patients with kidney cancer and a type of thyroid cancer responded well to this treatment. Real-world evidence suggests it might also benefit those with advanced bone cancers like osteosarcoma and Ewing sarcoma. Cabozantinib-s-malate blocks enzymes that tumors need to grow and stops the formation of blood vessels that supply tumors. These findings highlight its potential as a treatment option for rare cancers in young patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Srivandana Akshintala

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients up to 18 years old with specific rare tumors or sarcomas, including Wilms tumor, and some up to 30 years old. They must have measurable disease, adequate organ function, no prior treatment with MET/HGF inhibitors like XL184, and not be on certain medications that affect the liver or heart.

Inclusion Criteria

You have a rare cancer called Wilms tumor.

You have a type of thyroid cancer called medullary thyroid carcinoma (MTC).

This study does not include certain types of soft tissue cancers such as alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CCS).

Exclusion Criteria

Inability to comply with safety monitoring requirements

Invasive procedures within specified timeframes

Significant traumatic injury within 28 days prior to enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib-s-malate orally on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 6 cycles (24 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up at 30 days, every 6 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib-S-malate

Trial Overview The effectiveness of Cabozantinib-S-Malate is being tested in this phase II trial. It's aimed at treating children and young adults whose tumors are recurrent, resistant to therapy or newly diagnosed without known curative options.

How Is the Trial Designed?

Group I: Treatment (cabozantinib s-malate) Experimental Treatment 3 Interventions

Patients receive cabozantinib-s-malate orally (PO) on a continuous dosing schedule using a dosing nomogram on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cabozantinib is an effective multi-tyrosine kinase inhibitor approved for advanced renal cell carcinoma, showing significant benefits in progression-free and overall survival in two major clinical trials.

The phase III METEOR trial demonstrated cabozantinib's superiority over everolimus, while the phase II CABOSUN trial showed it outperformed sunitinib as a first-line treatment, highlighting its role in current treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Management of Metastatic Clear Cell Renal Cell Carcinoma. Vecchio, SJD., Ellis, RJ.[2020]

Cabozantinib demonstrated significant anticancer activity, particularly in ovarian cancer (21.7% objective response rate) and castration-resistant prostate cancer, which showed a median progression-free survival of 5.5 months compared to 1.4 months for placebo.

The trial involved 526 patients, and while cabozantinib showed promising efficacy, nearly half of the patients (48.7%) required dose reductions due to adverse events, with common severe side effects including fatigue, diarrhea, and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Schöffski, P., Gordon, M., Smith, DC., et al.[2018]

In a Phase 1 study involving 12 patients with relapsed osteosarcoma and Ewing sarcoma, the combination of cabozantinib, topotecan, and cyclophosphamide showed acceptable toxicity levels, with manageable dose-limiting toxicities observed.

The treatment resulted in one partial response and stable disease in seven patients, suggesting that this combination therapy may provide potential disease control in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. Campbell, K., Posner, A., Chen, N., et al.[2023]

Cabozantinib showed minimal efficacy in treating recurrent clear cell ovarian, fallopian tube, or primary peritoneal cancer, with only 23% of patients achieving progression-free survival of 6 months or more, and no objective tumor responses observed in a study of 13 patients over 19 months.

The treatment was associated with significant safety concerns, including thromboembolic events in multiple patients, highlighting the need for careful monitoring of side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of single-agent cabozantinib in patients with recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer (NRG-GY001). Konstantinopoulos, PA., Brady, WE., Farley, J., et al.[2023]

Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of the 25 heavily pretreated participants.

The treatment demonstrated a median progression-free survival of 12.9 months and a median overall survival of 15.0 months, with a safety profile consistent with other similar therapies, indicating its potential as a viable option for advanced RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Choueiri, TK., Pal, SK., McDermott, DF., et al.[2021]

Cabozantinib demonstrated clinical activity in patients with non-small-cell lung carcinoma (NSCLC), showing a 10% objective response rate and a 38% overall disease-control rate after 12 weeks of treatment, particularly in patients with KRAS mutations.

The treatment was associated with manageable safety concerns, with common grade 3/4 adverse events including fatigue and palmar-plantar erythrodysesthesia, although there was one serious treatment-related adverse event (hemorrhage) reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non-small-cell Lung Carcinoma. Hellerstedt, BA., Vogelzang, NJ., Kluger, HM., et al.[2019]

In a phase II study involving 52 women with hormone receptor-positive breast cancer and bone metastases, cabozantinib showed a 38% partial response rate on bone scans, indicating its potential effectiveness in this patient population.

The treatment resulted in a median progression-free survival of 4.3 months and a median overall survival of 19.6 months, with manageable side effects, primarily hypertension and anorexia, suggesting that cabozantinib could be a viable option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases. Xu, J., Higgins, MJ., Tolaney, SM., et al.[2021]

Cabozantinib is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, showing potential advantages over single-receptor TKIs.

The article reviews clinical trial data and management strategies for common adverse events associated with cabozantinib, highlighting its expanding use in treating various cancers such as prostate, hepatocellular, and lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. Markowitz, JN., Fancher, KM.[2019]

In a retrospective analysis of 16 adult patients with advanced osteosarcoma and Ewing sarcoma, cabozantinib showed antitumor activity, with 9 out of 16 patients achieving stable disease and a median progression-free survival of 5 months.

While cabozantinib was associated with common side effects like fatigue and weight loss, it also resulted in one serious adverse event (cerebral hemorrhage), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data on Cabozantinib in Advanced Osteosarcoma and Ewing Sarcoma Patients: A Study from the Hellenic Group of Sarcoma and Rare Cancers. Kokkali, S., Kyriazoglou, A., Mangou, E., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02867592

Study Details | NCT02867592 | Cabozantinib-S-Malate in ... ... Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors. Conditions. Adrenal Cortical CarcinomaAlveolar Soft Part SarcomaCentral Nervous ...

2. withpower.com withpower.com/trial/phase-3-hepatoblastoma-4-2017-9b107

Cabozantinib for Rare Cancers in Young Patients You have a rare cancer called Wilms tumor. You have a type of thyroid cancer called medullary thyroid carcinoma (MTC).

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.10010

Phase 2 trial of cabozantinib in children and young adults ... In the rare tumor stratum (n = 23), 1/4 patients with renal cell carcinoma, 1/1 patients with RET fusion positive papillary thyroid cancer had a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9918141/

Real-World Data on Cabozantinib in Advanced Osteosarcoma ... Real-World Data on Cabozantinib in Advanced Osteosarcoma and Ewing Sarcoma Patients: A Study from the Hellenic Group of Sarcoma and Rare Cancers.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20382994

Clinical Trials This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have come ...

6. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/c/NCT02867592.html

Cabozantinib-S-Malate in Treating Younger Patients With ... This phase II trial studies how well cabozantinib-s-malate works in treating younger patients with sarcomas, Wilms tumor, or other rare tumors that have ...