Clinical trial · Interventional
Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies
A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Cancer | Malignant Neoplasm | ALIAS | 0.90 |
| Lymphoma | Lymphoma | ONTOLOGY_EXACT | 0.90 |
| Thyroid Carcinoma | Thyroid Gland Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| XL184 | Drug | Cabozantinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- 1
- interventionNames
- Drug: XL184
Primary outcomes (2)
- measure
- Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184
- timeFrame
- Assessed during periodic visits
- measure
- Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184
- timeFrame
- Assessed during periodic visits
Secondary outcomes (3)
- measure
- Long-term safety/tolerability of XL184 after oral administration for up to 1 year
- timeFrame
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Histologically confirmed advanced malignancy (solid tumor or lymphoma) that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective * Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 * Life expectancy greater than 3 months * Adequate organ and marrow function * Written informed consent * Use of acceptable methods of contraception during the course of the study and for 3 months after completion of study * In the MTD expanded cohort: at least 20 subjects with metastatic and/or advanced/locally recurrent Medullary Thyroid Cancer not appropriate for surgical resection with measurable disease as defined by RECIST Exclusion Criteria: * Chemotherapy, immunotherapy or radiation within 4 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first scheduled dose of XL184 * Administration of an investigational drug within 30 days of the first dose of XL184 * Subject has not recovered from adverse events due to investigational agents or other medications administered more than 4 weeks before study enrollment * Known brain metastases * Uncontrolled intercurrent illness * Pregnancy or breastfeeding * Known HIV positive * Known allergy or hypersensitivity to any of the components of the XL184 formulation
References
Publications (3)
- DERIVEDKurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D, Sherman S. Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 2013 Sep;24(9):2256-61. doi: 10.1093/annonc/mdt177. Epub 2013 May 14. PMID 23676418
- DERIVEDKim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013 Oct;23(10):1277-83. doi: 10.1089/thy.2013.0057. Epub 2013 Jul 17. PMID 23489023
- DERIVEDKurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. PMID 21606412