Clinical Trials /

Study of CLR457 Administered Orally in Adult Patients With Advanced Solid Malignancies

NCT02189174

Description:

To estimate the maximum tolerated dose (MTD) or recommended dose for phase II (RP2D) of CLR457 and to investigate the anti-tumor activity of CLR457

Related Conditions:
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of CLR457 Administered Orally in Adult Patients With Advanced Solid Malignancies
  • Official Title: A Phase I/II Multicenter, Open-label Study of CLR457, Administered Orally in Adult Patients With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CCLR457X2101
  • NCT ID: NCT02189174

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
CLR457CLR457

Purpose

To estimate the maximum tolerated dose (MTD) or recommended dose for phase II (RP2D) of CLR457 and to investigate the anti-tumor activity of CLR457

Trial Arms

NameTypeDescriptionInterventions
CLR457Experimental
  • CLR457

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent must be obtained prior to any screening procedures

          -  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 positive (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: non-small cell lung cancer harboring
             cMET activation and/or EGFR mutation. Up to 3 lines of chemotherapy allowed in
             advanced/metastatic setting.

          -  ECOG Performance Status ≤ 2.

          -  Availability of a representative formalin fixed paraffin embedded tumor tissue sample.
             If archival tumor sample is not available, a newly obtained tumor sample needs to be
             submitted instead.

        Exclusion Criteria:

          -  Brain metastasis unless treated and neurologically stable

          -  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) or alanine aminotransferase (ALT) ≥ 2.5 x ULN

          -  For patients with tumor involvement of the liver AST 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 109/L

          -  Hemoglobin (Hgb) < 9 g/dL

          -  Absolute Neutrophil Count (ANC) < 1.5 x 109/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 ventricular 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

               -  Peripheral neuropathy CTCAE Grade ≥2

               -  History of pancreatitis of any grade

               -  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

               -  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 pump inhibitors unless these
                  medications can be discontinued at least a week prior to start of treatment.

        Other protocol-defined inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of DLT
Time Frame:First 28 days of dosing
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of Adverse Events (AEs) and Serious Advers Events (SAEs)
Time Frame:Continously throughout the study until 30 days after treatment discontinuation
Safety Issue:
Description:
Measure:Severity of AEs and SAEs and dose reductions and interruptions
Time Frame:Continously throughout the study until 30 days after treatment discontinuation
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:Baseline, every 8 weeks until discontinuation for an expected average of 4 months
Safety Issue:
Description:per RECIST v1.1
Measure:Progression free survival (PFS)
Time Frame:Baseline, every 8 weeks until discontinuation for an expected average of 4 months
Safety Issue:
Description:per RECIST v1.1
Measure:Best overall response (BOR)
Time Frame:Baseline and every 8 weeks for an expected average of 4 months
Safety Issue:
Description:per RECIST v1.1
Measure:Plasma concentration and Pharmacokinetics (PK) parameters of CLR457
Time Frame:During phase I: Baseline; Cycle 1 (C1) Day 1 (D1), 2, 8, 15, 16 and 22; Cycle 2 Day 1, 2, from Cycle 3 to cycle 6 on Day 1 During Phase II: Baseline; Cycle 1 Day 1, 2, 8, 15, 16 and 22
Safety Issue:
Description:Parameters including but not limited to Cmax, Cmin, AUCinf, AUCtlast, AUCtau and T1/2
Measure:Changes from baseline in glucose metabolism markers (fasting glucose and insulin)
Time Frame:For Phase I and II C1D1, C1D2, C1D15, C1D16 and for Phase I only C2D1 and C2D2
Safety Issue:
Description:
Measure:Pre- and post- treatment immunohistochemistry of PI3K pathway molecules in newly obtained paired tumor samples
Time Frame:Baseline, C2D1
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Solid tumor,
  • breast cancer,
  • lung cancer,
  • endometrial cancer

Last Updated

June 6, 2017