A Phase I/II, Open Label, Dose Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of RAF265 (CHIR-265) Administered Orally to Patients with Locally Advanced or Metastatic Melanoma.
- Conditions
- melanomaskin cancer10040900
- Registration Number
- NL-OMON33745
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
Age > 18 years;Histologically confirmed diagnosis of locally advanced or metastatic melanoma (for cutaneous melanoma American Joint Committee on Cancer (AJCC) Stage IIIb to IV, pathologic Stage III and IV for noncutaneous melanoma ), (see Appendix 1 for the AJCC Staging System for Cutaneous Melanoma).;Must have either archival tumor tissue or tumor that can be biopsied in order to determine whether it contains mutated or wild-type BRAF.;Evidence of measurable disease.;ECOG 0-1
Previous therapy with the following molecularly-targeted agents: MEK inhibitors VEGF or VEGFR inhibitors, RAF inhibitors;Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.;Clinically significant cardiac disease including congestive heart failure.;Previous or concurrent malignancy except adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.;Chronic anticoagulation therapy with full strength acetylsalicylic acid, warfarin, sodium, or heparin;History of thromboembolic or cerebrovascular events within the last 12 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.;Prior acute or chronic pancreatitis of any etiology.;Prior intra or extrahepatic biliary obstruction within the previous 12 months, or history of malignant obstruction requiring a biliary stent, unless stably treated with no prior obstruction or blockage of the stent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- The number of DLTs (phase I)<br /><br>- Safety profile (frequency and severity of AEs, laboratory-test results, ECG,<br /><br>ECHO, vital signs and weight) of RAF265 administered orally to patients with<br /><br>locally advanced or metastatic melanoma.<br /><br>- plasma PK levels of orally administered RAF265 (including but not limited to<br /><br>area under the curve (AUC), half-life [t1/2], observed maximum plasma<br /><br>concentration [Cmax], time<br /><br>at which maximum concentration is observed [tmax], and pre-dose plasma<br /><br>concentration<br /><br>[Cmin])<br /><br>- Best tumor response to treatment according to the RECIST criteria</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Progression-free survival<br /><br>- For each patient with a response to therapy, duration of response will be<br /><br>calculated.<br /><br>- Relationships between antitumor activity, BRAF, NRAS, c-KIT, p53, CDKN2A and<br /><br>PTEN mutation status (if analyzed), pharmacodynamic markers, and drug exposure<br /><br>levels will be explored.<br /><br>- Response rate at the MTD and/or OBD will be summarized for patients with or<br /><br>without BRAF mutations.<br /><br>- K-trans will be summarized for its change from baseline.</p><br>