A Phase I, multi-center, open label, dose escalation study of LEQ506, an oral Smoothened inhibitor, in patients with advanced solid tumors
- Conditions
- Solid tumors / different types of advanced cancer10027655
- Registration Number
- NL-OMON36627
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
- Dose escalation phase: patients with a with a histologically or cytologically confirmed solid tumor, who have progressed despite standard therapy or for which no standard therapy exists. Patients with recurrent or refractory Medullo Blastoma (MB) and patients with metastatic or locally advanced Basel Cell Carcinoma (BCC) that cannot be with local therapy.
- Expansion phase: patients with tumors that are characterized by Hedgehog pathway activation, such as recurrent or refractory MB or metastatic or locally advanced BCC
- WHO performance status *2.
- Required baseline laboratory values:
*Absolute Neutrophil Count *1.5x109/L
*Hemoglobin * 9 g/dl <= 5.58 mmol/l
*Platelets * 80x109/L
*AST/SGOT and ALT/SGPT * 2.5 x Upper Limit of Normal (ULN) or * 5.0 x ULN if liver metastases are present
*Serum bilirubin * 1.5 x ULN
*Serum creatinine * 1.5 x ULN or 24-hour clearance * 50 ml/min.
- Patients must have fully recovered from the effects of prior major surgery and from any acute toxic effects of prior chemotherapy and radiotherapy.
- A negative serum pregnancy test * 72 hours before starting study treatment
- History of primary central nervous system tumors or symptomatic brain metastases (except recurrent MB). However, patients with resected brain metastasis with no radiological evidence of disease or with stable brain metastasis with no evidence of progression are eligible. Such patients must have no need for treatment with steroids or anti-epileptic medications.
- Known diagnosis of HIV or Hepatitis C
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of LEQ506
- Any unresolved nausea, vomiting, or diarrhea CTCAE grade >1.
- Impaired cardiac function or clinically significant cardiac diseases, including any of the
following:
1) Acute myocardial infarction or angina pectoris * 3 months prior to starting study drug
2) QTcF > 450 msec for males and > 470 msec for females on screening ECG
3) Medical history of clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension)
- Any other concurrent severe and/or uncontrolled concomitant medical condition (e.g. uncontrolled diabetes, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
- Systemic anti-cancer treatment or radiotherapy < 2 weeks before the first dose of study treatment
(* 4 weeks for monoclonal antibodies).
- Prior treatment with investigational agents * 4 weeks or * 5 x their half-lives (whichever is longer) before the first dose of study treatment.
- Treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5
- Treatment with medications that are known to be substrates of CYP3A4/5 or CYP2C9 and that have low therapeutic indices.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Frequency of dose-limiting toxicities (DLTs)</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Safety: Adverse drug reactions and serious adverse drug reactions, changes in<br /><br>hematology and chemistry values (specifically those associated with hepatic and<br /><br>renal function), assessment of physical examinations, vital signs and ECG's<br /><br>* Pharmacokinetics parameters<br /><br>* Pharmacodynamics: Post-treatment changes in Gli1 mRNA expression in normal<br /><br>skin and tumor samples<br /><br>* Efficacy: Tumor response using RECIST for patients with solid tumors and<br /><br>using the Neuro-Oncology Criteria of Tumor Response for patients with Medullo<br /><br>Blastoma</p><br>