Last reviewed · How we verify
Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors
Phase 1 trial testing Cabozantinib S-malate in Recurrent Malignant Solid Neoplasm in 41 participants. Completed in 31 December 2019.
| Lead sponsor | National Cancer Institute (NCI) |
|---|---|
| Phase | Phase 1 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | na |
| Design | single group |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 41 |
| Start date | 14 November 2012 |
| Primary completion | 31 December 2018 |
| Estimated completion | 31 December 2019 |
| Sites | 23 locations across Canada, United States |
National Cancer Institute (NCI)
Adults 2 to 18, any sex, with Recurrent Malignant Solid Neoplasm or Recurrent Melanoma. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Maximum dose at which fewer than one-third of toxicity-evaluable patients experience a dose limiting toxicity during cycle 1 of therapy.
| Group | Value | 95% CI |
|---|---|---|
| Treatment (Cabozantinib S-malate) | 40 |
Number of toxicity-evaluable patients who experience a dose limiting toxicity during cycle 1 of therapy stratified by dose level and study part.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | 0 | |
| Part A Dose Level 2: 40 mg/m^2 | 0 | |
| Part A Dose Level 3: 55 mg/m^2 | 1 | |
| Part B Dose Level 2: 40 mg/m^2 | 1 | |
| Part PK Dose Level 2: 40 mg/m^2 | 4 | |
| Part PK Dose Level 3: 55 mg/m^2 | 2 |
Median (min, max) clearance of cabozantinib stratified by dose level and study part post-dose in cycle 1, day 1.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | 1641.7 | 1020.4 – 2222.2 |
| Part A Dose Level 2: 40 mg/m^2 | 1724.1 | 1120.4 – 4477.6 |
| Part A Dose Level 3: 55 mg/m^2 | 3013.8 | 1556.4 – 4366.8 |
| Part B Dose Level 2: 40 mg/m^2 | 2281.4 | 2247.2 – 2461.5 |
| Part PK Dose Level 2: 40 mg/m^2 | 2668.6 | 1252.6 – 4801.9 |
| Part PK Dose Level 3: 55 mg/m^2 | 1363.8 | 1327.4 – 1486.4 |
Number of response-evaluable patients with response (CR or PR) determined by RECIST guideline (version 1.1) including CR: disappearance of all target and non-target lesions; PR: at least 30% decrease in sum of diameters of target lesions.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | 0 | |
| Part A Dose Level 2: 40 mg/m^2 | 0 | |
| Part A Dose Level 3: 55 mg/m^2 | 1 | |
| Part B Dose Level 2: 40 mg/m^2 | 2 | |
| Part PK Dose Level 2: 40 mg/m^2 | 0 | |
| Part PK Dose Level 3: 55 mg/m^2 | 1 |
Median (95% CI) time to death stratified by dose level and study part.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | 576 | 48 – 695 |
| Part A Dose Level 2: 40 mg/m^2 | 1034 | 1034 – NA |
| Part A Dose Level 3: 55 mg/m^2 | 869 | 163 – 1562 |
| Part B Dose Level 2: 40 mg/m^2 | 256 | 190 – 321 |
| Part PK Dose Level 2: 40 mg/m^2 | 737 | 115 – 1617 |
| Part PK Dose Level 3: 55 mg/m^2 | 24 | 24 – NA |
Median (Min, Max) of change for VEGF-R2 sample from baseline to the day 21 or 28 stratified by dose level and study part.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | -1121.2 | -1561.4 – -64.8 |
| Part A Dose Level 2: 40 mg/m^2 | -2249.7 | -4385.4 – -764.1 |
| Part A Dose Level 3: 55 mg/m^2 | -2087.3 | -3664.6 – -287.8 |
| Part B Dose Level 2: 40 mg/m^2 | -1287.1 | -2192.0 – -702.5 |
| Part PK Dose Level 2: 40 mg/m^2 | -1742.2 | -3409.7 – -221.2 |
| Part PK Dose Level 3: 55 mg/m^2 | -2519.4 | -4412.9 – -465.4 |
Number of patients with tumor markers CEA and/or calcitonin 2x ULN at baseline defined as CR (normalization of CEA or calcitonin) or PR (at least 50% decrease in CEA or CTN) at least 4 weeks apart.
| Group | Value | 95% CI |
|---|---|---|
| Part A Dose Level 1: 30 mg/m^2 | 0 | |
| Part B Dose Level 2: 40 mg/m^2 | 1 |
Time frame: Up to 5 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Part A Dose Level 1: 30 mg… | Part A Dose Level 2: 40 mg… | Part A Dose Level 3: 55 mg… | Part B Dose Level 2: 40 mg… | Part PK Dose Level 2: 40 m… | Part PK Dose Level 3: 55 m… |
|---|---|---|---|---|---|---|---|
| Dehydration | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Movements involuntary | Nervous system disorders | — | — | — | — | — | — |
| Abdominal distension | Gastrointestinal disorders | — | — | — | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — | — | — | — |
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Agitation | Psychiatric disorders | — | — | — | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — | — | — | — |
| Anorexia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — | — | — | — |
| Ataxia | Nervous system disorders | — | — | — | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — | — | — | — |
| Bone pain | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — | — | — | — |
| Depressed level of consciousness | Nervous system disorders | — | — | — | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — | — | — | — |
| Dysarthria | Nervous system disorders | — | — | — | — | — | — |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Ejection fraction decreased | Investigations | — | — | — | — | — | — |
| Enterocolitis infectious | Infections and infestations | — | — | — | — | — | — |
| Fatigue | General disorders | — | — | — | — | — | — |
| Headache | Nervous system disorders | — | — | — | — | — | — |
| Hydrocephalus | Nervous system disorders | — | — | — | — | — | — |
| Hypernatremia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypertension | Vascular disorders | — | — | — | — | — | — |
| Hypoglycemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Reaction | System | Part A Dose Level 1: 30 mg… | Part A Dose Level 2: 40 mg… | Part A Dose Level 3: 55 mg… | Part B Dose Level 2: 40 mg… | Part PK Dose Level 2: 40 m… | Part PK Dose Level 3: 55 m… |
|---|---|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | — | — | — | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — | — | — | — |
| Anemia | Blood and lymphatic system disorders | — | — | — | — | — | — |
| Fatigue | General disorders | — | — | — | — | — | — |
| Anorexia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Headache | Nervous system disorders | — | — | — | — | — | — |
| Hypoalbuminemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypothyroidism | Endocrine disorders | — | — | — | — | — | — |
| Nausea | Gastrointestinal disorders | — | — | — | — | — | — |
| Proteinuria | Renal and urinary disorders | — | — | — | — | — | — |
| Vomiting | Gastrointestinal disorders | — | — | — | — | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — | — | — | — | — |
| Alopecia | Skin and subcutaneous tissue disorders | — | — | — | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — | — | — | — |
| Diarrhea | Gastrointestinal disorders | — | — | — | — | — | — |
| Hyperglycemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypophosphatemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Lymphocyte count decreased | Investigations | — | — | — | — | — | — |
| Platelet count decreased | Investigations | — | — | — | — | — | — |
| White blood cell decreased | Investigations | — | — | — | — | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Dizziness | Nervous system disorders | — | — | — | — | — | — |
| Hypertension | Vascular disorders | — | — | — | — | — | — |
| Hypocalcemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hyponatremia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | — | — | — | — | — | — |
| Weight loss | Investigations | — | — | — | — | — | — |
| Alkaline phosphatase increased | Investigations | — | — | — | — | — | — |
| Dry skin | Skin and subcutaneous tissue disorders | — | — | — | — | — | — |
| Fever | General disorders | — | — | — | — | — | — |
| Hemoglobin increased | Investigations | — | — | — | — | — | — |
| Hypoglycemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypokalemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — | — | — | — |
| Pain in extremity | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Sinus tachycardia | Cardiac disorders | — | — | — | — | — | — |
| Agitation | Psychiatric disorders | — | — | — | — | — | — |
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Bruising | Injury, poisoning and procedural complications | — | — | — | — | — | — |
Most-reported serious reactions: Dehydration, Movements involuntary, Abdominal distension, Abdominal pain, Adult respiratory distress syndrome, Agitation, Alanine aminotransferase increased, Anorexia.
Data from ClinicalTrials.gov NCT01709435 adverse events section.
This phase I trial studies the side effects and best dose of cabozantinib S-malate in treating younger patients with solid tumors that have come back or no longer respond to treatment. Cabozantinib S-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
8 peer-reviewed publications reference this trial (live from Europe PMC):
Verify or expand the search:
Trials testing the same drug.
Currently open trials in the same condition.
Trials by the same sponsor.
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/NCT01709435.
Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing