This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02189174
First received: July 7, 2014
Last updated: June 6, 2017
Last verified: June 2017
  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

Condition Intervention Phase
Advanced Solid Tumor Drug: CLR457 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Multicenter, Open-label Study of CLR457, Administered Orally in Adult Patients With Advanced Solid Malignancies

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Incidence of DLT [ Time Frame: First 28 days of dosing ]
  • Objective response rate (ORR) as per RECIST v1.1 [ Time Frame: Baseline, every 8 weeks until discontinuation for an expected average of 4 months ]

Secondary Outcome Measures:
  • Incidence of Adverse Events (AEs) and Serious Advers Events (SAEs) [ Time Frame: Continously throughout the study until 30 days after treatment discontinuation ]
  • Severity of AEs and SAEs and dose reductions and interruptions [ Time Frame: Continously throughout the study until 30 days after treatment discontinuation ]
  • Duration of response (DOR) [ Time Frame: Baseline, every 8 weeks until discontinuation for an expected average of 4 months ]
    per RECIST v1.1

  • Progression free survival (PFS) [ Time Frame: Baseline, every 8 weeks until discontinuation for an expected average of 4 months ]
    per RECIST v1.1

  • Best overall response (BOR) [ Time Frame: Baseline and every 8 weeks for an expected average of 4 months ]
    per RECIST v1.1

  • 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 ]
    Parameters including but not limited to Cmax, Cmin, AUCinf, AUCtlast, AUCtau and T1/2

  • 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 ]
  • Pre- and post- treatment immunohistochemistry of PI3K pathway molecules in newly obtained paired tumor samples [ Time Frame: Baseline, C2D1 ]

Enrollment: 31
Study Start Date: August 2014
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CLR457 Drug: CLR457

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02189174

Locations
United States, Massachusetts
Massachusetts General Hospital SC-9
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center SC-4
New York, New York, United States, 90033
United States, Tennessee
Tennessee Oncology SC
Nashville, Tennessee, United States, 37203
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1X6
Japan
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277-8577
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02189174     History of Changes
Other Study ID Numbers: CCLR457X2101
Study First Received: July 7, 2014
Last Updated: June 6, 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Solid tumor,
breast cancer,
lung cancer,
endometrial cancer

ClinicalTrials.gov processed this record on August 17, 2017