Cabozantinib for Rare Cancers in Young Patients

Recruiting at 151 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)

109 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Cabozantinib-S-malate for rare cancers in young patients?

Research shows that cabozantinib, the active ingredient in Cabozantinib-S-malate, has shown antitumor activity in various cancers, including advanced osteosarcoma and Ewing sarcoma, with some patients experiencing stable disease outcomes. ^{1 2 3 4 5}

What safety data exists for cabozantinib in humans?

Cabozantinib has been tested in various cancers and is generally associated with side effects like fatigue, loss of appetite, weight loss, diarrhea, and skin reactions. In some cases, serious effects like cerebral hemorrhage have occurred, and dose adjustments were needed for some patients. ^{3 4 6 7 8}

How is the drug cabozantinib unique for treating rare cancers in young patients?

Cabozantinib is unique because it targets multiple proteins (tyrosine kinases) involved in cancer growth, such as MET and VEGF receptors, which can help stop the cancer from growing and spreading. This multi-target approach is different from many other treatments that might focus on just one pathway. ^{1 7 8 9 10}

What is the purpose of this trial?

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 back, do not respond to therapy, or are newly diagnosed. Cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth and tumor blood vessel growth.

Research Team

Srivandana Akshintala

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Cabozantinib in Hormone Receptor-Positive Breast Cancer with Bone Metastases. [2021]

3. Switzerland 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. [2023]

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

Phase 1 study of cabozantinib in combination with topotecan-cyclophosphamide for patients with relapsed Ewing sarcoma or osteosarcoma. [2023]

5. United States 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). [2023]

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

Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]

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

Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. [2018]

9. Australia pubmed.ncbi.nlm.nih.gov

Cabozantinib for the Management of Metastatic Clear Cell Renal Cell Carcinoma. [2020]

10. United States 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. [2019]