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NCT01755195

Cabozantinib for Adults With Advanced Soft Tissue Sarcoma

Completed Phase 2 Results posted Last updated 3 January 2024
What this trial tests

Phase 2 trial testing Cabozantinib in Refractory Soft Tissue Sarcomas in 55 participants. Completed in 11 September 2023.

Timeline
15 January 2013
Primary endpoint
30 September 2020
11 September 2023

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment55
Start date15 January 2013
Primary completion30 September 2020
Estimated completion11 September 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 120, any sex, with Refractory Soft Tissue Sarcomas. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response (Complete Response (CR)+Partial Response (PR) of Cabozantinib in Patients With Soft Tissue Sarcomas Primary · Date treatment consent signed to date off study, approximately 86 months and 3 days.

Objective response was assessed by the Response Evaluation Criteria in Solid Tumors RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

GroupValue95% CI
Cabozantinib11.14.2 – 22.6
Percentage of Participants With 6 Month Progression Free Survival (PFS) Primary · 6 months

Progression in participants with soft tissue sarcomas treated with cabozantinib was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.

GroupValue95% CI
Cabozantinib49.336.2 – 67.3
Mean Change From Baseline in Levels of Circulating Hepatocyte Growth Factor (HGF) Secondary · Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1

Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of HGF. HGF protein content (in picograms; pg) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.

Baseline to Cycle 1 Day 1
GroupValue95% CI
Cabozantinib-51.3-235.5 – 151.0
Baseline to Cycle 2 Day 1
GroupValue95% CI
Cabozantinib344.84.1 – 685.6
Mean Change From Baseline in Levels of Circulating Soluble Mesenchymal Epithelial Transition Factor (sMET) Secondary · Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1

Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of soluble MET (sMET). sMET protein content (in nanograms; ng) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.

Baseline to Cycle 1 Day 1
GroupValue95% CI
Cabozantinib-6.1-12.0 – -0.3
Baseline to Cycle 2 Day1
GroupValue95% CI
Cabozantinib16.43.4 – 29.4
Mean Change From Baseline in Levels of Circulating Vascular Endothelial Growth Factor A (VEGF-A) Secondary · Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1

Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of VEGF-A. VEGF-A protein content (in picograms; pg) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome.

Baseline to Cycle 1 Day 1
GroupValue95% CI
Cabozantinib5.6-3.6 – 14.7
Baseline to Cycle 2 Day 1
GroupValue95% CI
Cabozantinib32.56.5 – 58.5
Mean Change From Baseline in Levels of Circulating Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR-2) Secondary · Baseline to Cycle 1 Day 1 and baseline to Cycle 2 Day 1

Blood samples were collected before treatment on the first day of cycles 1 and 2 to determine circulating levels of soluble VEGFR2 (sVEGFR-2). sVEGFR-2 protein content (in nanograms; ng) in blood plasma (in milliliters; mL) was measured for each sample with a two-site immunoassay and the difference from before to after treatment for each patient was reported. A change in this biomarker from the baseline value has not been linked to clinical outcomes; that is, it is neither a good or a bad outcome..

Baseline to Cycle 1 Day 1
GroupValue95% CI
Cabozantinib-1.0-2.6 – 0.6
Baseline to Cycle 2 Day 1
GroupValue95% CI
Cabozantinib-10.9-13.5 – -8.4
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) Secondary · Date treatment consent signed to date off study, approximately 86 months and 3 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

GroupValue95% CI
Cabozantinib53

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 86 months and 3 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cabozantinib
Serious: 14/54 (26%)
Deaths: 3/54

Serious adverse events (29 terms)

ReactionSystemCabozantinib
Thromboembolic eventVascular disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Small intestinal obstructionGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
Cerebrospinal fluid leakageNervous system disorders
DehydrationMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
General disorders and administration site conditions - Other, feverGeneral disorders
HeadacheNervous system disorders
HematuriaRenal and urinary disorders
HypophosphatemiaMetabolism and nutrition disorders
Muscle weakness trunkMusculoskeletal and connective tissue disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleuritic painRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Serum amylase increasedInvestigations
StrokeNervous system disorders
Supraventricular tachycardiaCardiac disorders
SyncopeNervous system disorders
Other adverse events (233 terms — click to expand)

ReactionSystemCabozantinib
HypertensionVascular disorders
Alanine aminotransferase increasedInvestigations
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
DiarrheaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
FatigueGeneral disorders
NauseaGastrointestinal disorders
Alkaline phosphatase increasedInvestigations
HeadacheNervous system disorders
AnorexiaMetabolism and nutrition disorders
HypothyroidismEndocrine disorders
White blood cell decreasedInvestigations
ConstipationGastrointestinal disorders
DysgeusiaNervous system disorders
HypoalbuminemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
Platelet count decreasedInvestigations
Weight lossInvestigations
HypophosphatemiaMetabolism and nutrition disorders
Mucositis oralGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
ProteinuriaRenal and urinary disorders
DizzinessNervous system disorders
Dry mouthGastrointestinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Lipase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
DyspepsiaGastrointestinal disorders
PainGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Skin hypopigmentationSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
BruisingInjury, poisoning and procedural complications
HoarsenessRespiratory, thoracic and mediastinal disorders
Oral painGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders

Most-reported serious reactions: Thromboembolic event, Vomiting, Abdominal pain, Nausea, Pleural effusion, Small intestinal obstruction, Anemia, Cerebrospinal fluid leakage.

Data from ClinicalTrials.gov NCT01755195 adverse events section.

Sponsor's own description

Background: \- Cabozantinib is a cancer treatment drug that blocks the growth of new blood vessels in tumors. It can also block a chemical on tumor cells that allows the cells to grow. A similar drug, pazopanib, is used to treat types of cancer known as sarcomas. Researchers want to see if cabozantinib can be an effective treatment for types of soft tissue sarcoma that have not responded to earlier treatments. Objectives: \- To test the effectiveness of cabozantinib for soft tissue sarcomas that have not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have soft tissue sarcomas that have not responded to standard treatments. Design: * Participants will be screened with a physical exam and medical history. Blood samples will be collected. Imaging studies and other tests will be used to study the tumor before the start of treatment. * Participants will take cabozantinib tablets daily for 28-day cycles of treatment. The tablets should be taken whole on an empty stomach. * Treatment will be monitored with frequent blood tests and imaging studies. * Participants will continue to take cabozantinib for as long as the tumor does not become worse and the side effects are not too severe.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.
    Tricoli JV, Blair DG, Anders CK, Bleyer WA, et al · · 2016 · cited 107× · PMID 26849082 · DOI 10.1002/cncr.29871
  2. BDNF and its signaling in cancer.
    Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, et al · · 2023 · cited 48× · PMID 36173463 · DOI 10.1007/s00432-022-04365-8
  3. The treatment landscape in thyroid cancer: a focus on cabozantinib.
    Weitzman SP, Cabanillas ME. · · 2015 · cited 24× · PMID 26316818 · DOI 10.2147/cmar.s68373
  4. Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.
    Just MA, Van Mater D, Wagner LM. · · 2021 · cited 23× · PMID 33894051 · DOI 10.1002/pbc.29084
  5. Advances in treatment of alveolar soft part sarcoma: an updated review.
    Fujiwara T, Kunisada T, Nakata E, Nishida K, et al · · 2023 · cited 22× · PMID 37626447 · DOI 10.1093/jjco/hyad102
  6. Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas.
    O'Sullivan Coyne G, Kummar S, Hu J, Ganjoo K, et al · · 2022 · cited 22× · PMID 34716194 · DOI 10.1158/1078-0432.ccr-21-2480
  7. Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.
    Yavuz S, Apolo AB, Kummar S, del Rivero J, et al · · 2014 · cited 22× · PMID 24724719 · DOI 10.1089/thy.2013.0621
  8. The angiogenic asset of soft tissue sarcomas: a new tool to discover new therapeutic targets.
    Rocchi L, Caraffi S, Perris R, Mangieri D, et al · · 2014 · cited 19× · PMID 25236925 · DOI 10.1042/bsr20140075

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01755195.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing