A phase I/II multicenter, open-label study of CLR457, administered orallyin adult patients with advanced solid malignancies
- Conditions
- Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 17.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Advanced solid malignancies
- Registration Number
- EUCTR2014-000316-34-FR
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 163
1. Written informed consent must be obtained prior to any screening procedures
2. Patient (male or female) = 18 years of age
3. Phase I: Patients with advanced/metastatic solid tumors, with measurable or non measurable disease as determined by modified RECIST version 1.1 who have progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, who have tumors harboring one of the following: confirmed PIK3CA mutation or amplification, PTEN loss of function, EGFR mutation, cMET activation and/or HER2 overexpression. Endometrial carcinoma will not be selected for any molecular status.
Phase II: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by modified RECIST version 1.1, who progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists,
fitting in one of the following groups:
Group 1: patients with PIK3CA mutated or amplified ER + breast cancer
Group 2: patients with endometrial carcinoma (not selected for any molecular status)
Group 3: patients with solid tumors (with the exception of PIK3CA mutant/amplified ER+ breast cancer and endometrial carcinoma) harboring PIK3CA mutation or amplification/any PTEN status
Group 4: patients with solid tumors (with the exception of endometrial carcinoma) harboring PTEN loss of function/ PIK3CA wild type
Group 5: patients with non-small cell lung cancer harboring cMET activation and/or EGFR mutation
4. Up to 3 chemotherapies in advanced/metastatic setting allowed for Phase II patients.
5. ECOG Performance Status = 2.
6. Availability of a representative formalin fixed paraffin embedded tumor tissue sample. If archival tumor specimen is not available, a newly obtained tumor specimen needs to be submitted instead.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53
1. Brain metastasis unless treated and neurologically stable
2. Patient having out of range laboratory values defined as:
Hepatic and renal function:
• Serum total Bilirubin=1.5 x ULN (upper limit of normal) or aspartate aminotransferase (AST) and alanine aminotransferase (ALT= 2.5 x ULN)
• Patients with tumor involvement of the liver must have AST and/or ALT >5 x ULN
• For patients with Gilbert's syndrome total bilirubin >2.5 x ULN
• Serum creatinine >1.5 x ULN and/or measured or calculated creatinine clearance < 75% LLN (lower limit of normal)
Bone marrow function:
• Platelets < 100 x 10^9/L
• Hemoglobin (Hgb) < 9 g/dL
• Absolute Neutrophil Count (ANC) < 1.5 x 10^9/L
Cardiac function:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure (CHF) requiring treatment (NYH grade = 2), hypertension or arrhythmia
• left ventricule ejection fraction (LVEF) < 45% as determined by MUGA scan or ECHO
• QTcF >480 msec on screening ECG or congenital long QT syndrome
• Acute myocardial infarction (AMI) or unstable angina pectoris = 3 months prior to study entry
3. Peripheral neuropathy CTCAE Grade = 2.
4. History of pancreatitis of any grade.
5. Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with Fasting Plasma Glucose (FPG) = 140 mg/dL / 7.8 mmol/L
6. Patients receiving treatment with medications that are known to be
1) strong inhibitors or inducers of CYP3A4/5; 2) CYP2C9 substrate with narrow therapeutic index; 3) QT prolonging agents; 4) proton pomp inhibitors unless these medications can be discontinued at least a week prior to start of treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To estimate the MTD or RP2D of CLR457 (dose escalation phase)<br>2. To investigate the anti-tumor activity of CLR457 (Phase II);Secondary Objective: 1. To characterize the safety and tolerability of CLR457 treatment<br>2. To determine the single and multiple dose PK profile of CLR457<br>3. To further investigate the anti-tumor activity of CLR457<br>4. To assess the PI3K pathway inhibition by CLR457;Primary end point(s): 1- Incidence of DLT <br>2- Objective response rate (ORR) per RECIST v1.1 by investigator assessment;Timepoint(s) of evaluation of this end point: 1- First 28 days of dosing<br>2- Baseline and every 8 weeks
- Secondary Outcome Measures
Name Time Method