Cabozantinib for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Anticoagulants, Antiplatelets
Disqualifiers: Uncontrolled hypertension, Brain metastases, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity.
A phase II study looks at how effective a medication is at treating a specific type of cancer and collects information on the side effects of the study treatment.
RET, ROS1, or NTRK fusion or increased MET or AXL activity gene leads to lung cancer cell growth. Cabozantinib is an oral medicine that inhibits of RET, ROS1, NTRK, MET, and AXL. In addition, this drug interferes with other cell pathways that also cause cancer cells to grow, form new blood vessels, and spread to other organs of the body. The goal of using cabozantinib is to shrink the cancer and to prevent it from growing
Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good idea of what side-effects it causes and can anticipate them.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but it does mention that you cannot have taken any systemic anticancer agents within 3 weeks of starting the study. If you are on anticoagulants, you may need to adjust your treatment, as only low-dose aspirin and certain types of heparin are allowed.
What data supports the effectiveness of the drug Cabozantinib for treating non-small cell lung cancer?
Cabozantinib has shown effectiveness in treating other cancers, such as advanced hepatocellular carcinoma and thyroid cancer, by targeting specific proteins involved in cancer growth. This suggests it may also be beneficial for non-small cell lung cancer, as it targets similar pathways.
12345Is Cabozantinib generally safe for humans?
Cabozantinib, also known as Cabometyx, has been studied for various conditions, and while specific safety data for non-small cell lung cancer isn't provided here, it has been used in other cancers with a known safety profile. Like many cancer treatments, it may have side effects, so it's important to discuss potential risks with your doctor.
678910How is the drug Cabozantinib unique for treating non-small cell lung cancer?
Cabozantinib is unique for treating non-small cell lung cancer because it targets the MET gene, which is altered in some patients, making it a potential option for those with specific genetic mutations (MET exon 14 skipping mutations) that drive the cancer.
1112131415Eligibility Criteria
Adults with advanced non-small cell lung cancer that is metastatic or unresectable and have specific genetic changes (RET, ROS1, NTRK fusions, MET or AXL overexpression/amplification/mutation). Must be able to perform daily activities well (Karnofsky >70%), have good organ function, not pregnant, agree to use contraception. Excludes those with recent significant illnesses/treatments or known allergies to cabozantinib.Inclusion Criteria
I understand the study requirements and have signed the consent form.
Your disease can be measured using a specific set of guidelines called RECIST1.1.
I am able to care for myself and engage in normal activities.
+6 more
Exclusion Criteria
I have had serious bleeding or a tumor affecting major blood vessels in the last 28 days.
I have been treated with cabozantinib before.
I haven't had radiation for bone or brain cancer, or any radiation treatment, in the last 2 to 4 weeks.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cabozantinib to assess its effects on tumors with RET, ROS1, or NTRK fusion, or increased MET or AXL activity
12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
3 years
Participant Groups
The trial tests the effects of an oral drug called Cabozantinib on patients with certain gene changes in their lung cancer cells. It's a phase II study which means it focuses on how effective this treatment is and monitors side effects closely.
1Treatment groups
Experimental Treatment
Group I: CabozantinibExperimental Treatment1 Intervention
This will be a single-institution, open label, two-stage, single agent trial of cabozantinib in patients with advanced NSCLCs.atients in GROUP A will have tumors with a RET fusion. Patients in GROUP B will have tumors with an NTRK fusion, or MET or AXL overexpression, amplication, or mutatation. Patients in GROUP C will have tumors with a ROS1 fusion. Patients in GROUP D will have tumors with a RET fusion and have progressed on a selective RET TKI.
Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇺🇸 Approved in United States as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇨🇦 Approved in Canada as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇯🇵 Approved in Japan as Cabometyx for:
- Renal cell carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering WestchesterHarrison, NY
Memorial Sloan Kettering MonmouthMiddletown, NJ
Memorial Sloan Kettering NassauUniondale, NY
Memorial Sloan Kettering Basking RidgeBasking Ridge, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
ExelixisIndustry Sponsor
References
Results of a Phase II Placebo-controlled Randomized Discontinuation Trial of Cabozantinib in Patients with Non-small-cell Lung Carcinoma. [2019]Cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against MET, vascular endothelial growth factor receptor 2, AXL, ROS1, and RET was assessed in patients with non-small-cell lung carcinoma (NSCLC) as part of a phase II randomized discontinuation trial with cohorts from 9 tumor types.
New Indication for Cabozantinib. [2023]Cabozantinib (Cabometyx) is now approved to treat locally advanced or metastatic differentiated thyroid cancer that has progressed following prior vascular endothelial growth factor receptor-targeted therapy.
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives. [2021]Cabozantinib (Cabometyx®) is a potent multikinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor 2, the mesenchymal-epithelial transition factor (MET) receptor, and the "anexelekto" (AXL) receptor tyrosine kinase. It is approved for the treatment of advanced hepatocellular carcinoma (HCC) after failure of sorafenib in Europe (since November 2018) and in the USA (since January 2019). The approval of cabozantinib was based on results of the randomized, placebo-controlled, phase 3 CELESTIAL trial in patients with unresectable HCC, who received one or two prior lines of treatment including sorafenib. At the second planned interim analysis, the trial was stopped, because the primary end point overall survival was clearly in favor for cabozantinib. Additionally, median progression-free survival was superior to placebo. The most common ≥ grade 3 relevant adverse events in patients with HCC treated with cabozantinib were palmar-plantar erythrodysesthesia, hypertension, fatigue, and diarrhea. In this review, current data on cabozantinib for the treatment of patients with advanced HCC, with a focus on the management of common adverse events and ongoing clinical trials, are discussed.
Cabozantinib: A Multitargeted Oral Tyrosine Kinase Inhibitor. [2019]Cabozantinib is an oral small-molecule multitargeted tyrosine kinase inhibitor (TKI) that may confer an advantage over other TKIs that target a single receptor. It was approved by the U.S. Food and Drug Administration for the treatment of both advanced renal cell carcinoma and progressive metastatic medullary thyroid cancer, and it is being investigated for a wide array of other malignancies. Rationale for use, clinical trial data, and current recommendations for cabozantinib in renal cell cancer, thyroid cancer, prostate cancer, hepatocellular cancer, and lung cancer are detailed in this article. Common adverse events are reviewed, and management strategies for select adverse events are discussed. Implications for contemporary practitioners are also provided because use of this novel agent is likely to increase as more studies are completed.
Pharmaceutical Approval Update. [2020]Cabozantinib (Cabometyx) for advanced renal cell carcinoma; glycopyrrolate/formoterol fumarate (Bevespi Aerosphere) for chronic obstructive pulmonary disease; and ephedrine sulfate (Akovaz) for hypotension during anesthesia.
Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: an expert consensus. [2018]Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well as the favorable tolerability and safety profile observed. Recently published phase III data established crizotinib as a new standard of care for this NSCLC molecular subset. A consequence of such rapid approval, however, is the limited clinical experience and relative paucity of information concerning optimal therapy management. In this review, we discuss the development of crizotinib and the clinical relevance of its safety profile, examining crizotinib-associated adverse events in detail and making specific management recommendations. Crizotinib-associated adverse events were mostly mild to moderate in severity in clinical studies, and appropriate monitoring and supportive therapies are considered effective in avoiding the need for dose interruption or reduction in most cases. Therapy management of patients following disease progression on crizotinib is also discussed. Based on available clinical data, it is evident that patients may have prolonged benefit from crizotinib after Response Evaluation Criteria in Solid Tumors-defined disease progression, and crizotinib should be continued for as long as the patient derives benefit.
Multiple cardiotoxicities during osimertinib therapy. [2023]Label="INTRODUCTION" NlmCategory="BACKGROUND">The tyrosine-kinase inhibitor osimertinib is an oral anti-cancer agent that is used for the treatment of patients with metastatic non-small cell lung cancer harbouring sensitising EGFR mutations. Patients receiving osimertinib are at higher risk of developing cardiac toxicity, and here we present the case of a 72-year-old male who developed multiple cardiotoxicities during therapy (i.e. QTc prolongation, atrial fibrillation, heart failure).
Clinical Relevance of High Plasma Trough Levels of the Kinase Inhibitors Crizotinib, Alectinib, Osimertinib, Dabrafenib, and Trametinib in NSCLC Patients. [2023]the study aims to evaluate whether high plasma trough levels of the kinase inhibitors (K.I.s) crizotinib, alectinib, osimertinib, dabrafenib, and trametinib were associated with a higher risk of toxicity in non-small-cell lung cancer patients.
FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]On March 30, 2017, the U.S. Food and Drug Administration (FDA) approved osimertinib for the treatment of patients with metastatic, epidermal growth factor receptor (EGFR) T790M mutation-positive, non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed following EGFR tyrosine kinase inhibitor (TKI) therapy. Approval was based on demonstration of a statistically significant difference in the primary endpoint of progression-free survival (PFS) when comparing osimertinib with chemotherapy in an international, multicenter, open-label, randomized trial (AURA3). In this confirmatory trial, which enrolled 419 patients, the PFS hazard ratio for osimertinib compared with chemotherapy per investigator assessment was 0.30 (95% confidence interval 0.23-0.41), p < .001, with median PFS of 10.1 months in the osimertinib arm and 4.4 months in the chemotherapy arm. Supportive efficacy data included PFS per blinded independent review committee demonstrating similar PFS results and an improved confirmed objective response rate per investigator assessment of 65% and 29%, with estimated median durations of response of 11.0 months and 4.2 months, in the osimertinib and chemotherapy arms, respectively. Patients received osimertinib 80 mg once daily and had a median duration of exposure of 8 months. The toxicity profile of osimertinib compared favorably with the profile of other approved EGFR TKIs and chemotherapy. The most common adverse drug reactions (>20%) in patients treated with osimertinib were diarrhea, rash, dry skin, nail toxicity, and fatigue. Herein, we review the benefit-risk assessment of osimertinib that led to regular approval, for patients with metastatic NSCLC harboring EGFR TKI whose disease has progressed on or after EGFR TKI therapy.
Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective for treatment of EGFR- or ALK-mutated lung cancer. Nevertheless, they are associated with several unique toxicities. Although the available US Food and Drug Administration (FDA)-approved drug label can provide guidance for safety monitoring, its integration into clinical practice has not been previously described. We studied the conduct of safety monitoring activity (SMA) at a large academic institution. On the basis of FDA-approved drug labels, two drug-specific SMAs were identified for osimertinib, crizotinib, alectinib, or lorlatinib. Electronic medical records of patients initiated on these drugs from 2017 to 2021 were retrospectively reviewed. Each course of treatment was evaluated for the occurrence of SMAs and the corresponding adverse events. Analyses included 130 treatment courses from 111 unique patients. For each SMA evaluated, the prevalence of SMA conduct ranged from 10.0% to 84.6%. The most frequently conducted SMA was ECG for lorlatinib therapy and the least was creatine phosphokinase analysis for alectinib. We observed none of the assessed SMAs being conducted in 41 treatment courses (31.5%). EGFR inhibitor predicted a higher likelihood of both SMAs being conducted than ALK inhibitors (P = .02). Serious, grade 3 or 4 adverse events were observed in 21 treatment courses (16.2%), including one grade 4 transaminitis related to alectinib. On the basis of our experience, the conduct of SMA was more challenging to implement for ALK inhibitor than for EGFR inhibitor. Clinicians should be vigilant and review the FDA-approved drug label before prescribing.
Case series of MET exon 14 skipping mutation-positive non-small-cell lung cancers with response to crizotinib and cabozantinib. [2020]The mesenchymal-to-epithelial transition (MET) gene is altered and becomes a driver mutation in up to 5% of non-small-cell lung cancer (NSCLC). We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib. We identified cases of NSCLC with METex14 mutations using an institutionally developed or commercial next-generation sequencing assay. We assessed patient and disease characteristics by retrospective chart review. Some patients were treated off-label by the physician with crizotinib or cabozantinib, and tumor responses to these agents were assessed. A total of 15 patients with METex14-mutated NSCLC were identified, predominantly male (n=10) with a smoking history (60%) and a median age of 74.0 years. No other actionable somatic mutations were detected. Stage distribution included 26.7% stage I, 6.7% stage II, 6.7% stage III, and 60.0% stage IV. Among patients treated with crizotinib or cabozantinib (n=6), three patients showed partial response and one patient showed stable disease on the basis of RECIST criteria. Four patients experienced side effects requiring drug holiday, reduction, or cessation. Our findings highlight the diversity in presentation and histology of NSCLC with METex14 mutations, which were found in the absence of other actionable driver mutations. We observed evidence of tumor response to crizotinib and cabozantinib, supporting the previous reports that METex14 mutations in NSCLC are actionable driver events.
Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]Osimertinib is an irreversible tyrosine kinase inhibitor approved for the treatment of metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). In clinical trials, osimertinib has exhibited excellent activity and less toxicity compared to gefitinib, erlotinib and standard chemotherapy.
Osimertinib Treats CNS Metastases in NSCLC. [2022]The EGFR inhibitor osimertinib may be an effective therapy for patients with untreated non-small cell lung cancer who have brain metastases. In a recent study, the drug extended median progression-free survival and increased objective response rates compared with the first-generation EGFR inhibitors gefitinib and erlotinib.
Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report. [2022]Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib.
Early-onset interstitial pneumonitis in a patient with advanced non-small cell lung cancer treated with crizotinib and osimertinib. [2022]Both crizotinib and osimertinib have been reported to have an adverse effect of interstitial pneumonitis in the treatment of non-small cell lung cancer (NSCLC). Here, we report the case of a 60-year-old male patient with advanced NSCLC resistant to osimertinib. Crizotinib was administered in combination with osimertinib due to elevated mesenchymal epithelial transition (MET) copy number amplification. However, early-onset interstitial pneumonitis occurred within two days.