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

NCT02189174 | Terminated Phase 1

• 1 other identifier: CCLR457X2101
• Study Type: interventional
• Target: 31
• Locations: 5 countries
• Sites: 7

Brief Summary

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

Conditions

Advanced Solid Tumor

Keywords

Solid tumor,; breast cancer,; lung cancer,; endometrial cancer

Outcome Measures

Primary Outcomes (2)

• Incidence of DLT

  First 28 days of dosing

• Objective response rate (ORR) as per RECIST v1.1

  Baseline, every 8 weeks until discontinuation for an expected average of 4 months

Secondary Outcomes (8)

• Incidence of Adverse Events (AEs) and Serious Advers Events (SAEs)

  Continously throughout the study until 30 days after treatment discontinuation

• Severity of AEs and SAEs and dose reductions and interruptions

  Continously throughout the study until 30 days after treatment discontinuation

• Duration of response (DOR)

  Baseline, every 8 weeks until discontinuation for an expected average of 4 months

• Progression free survival (PFS)

  Baseline, every 8 weeks until discontinuation for an expected average of 4 months

• Best overall response (BOR)

  Baseline and every 8 weeks for an expected average of 4 months

Study Arms (1)

CLR457

EXPERIMENTAL

Drug: CLR457

Interventions

CLR457 DRUG

CLR457

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Massachusetts General Hospital SC-9

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering SC-4

New York, New York, 10017, United States

Location

Tennessee Oncology SC

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X6, Canada

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Singapore, 169610, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms; Lung Neoplasms; Endometrial Neoplasms

Interventions

CLR457

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase ll part of the study was not conducted as Novartis decided to terminate the study considering safety and tolerability concerns and limited clinical activity.

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 14, 2014
• Study Start: August 7, 2014
• Primary Completion: November 12, 2015
• Study Completion: November 12, 2015
• Last Updated: December 3, 2021

Record last verified: 2021-12

Locations

SG (1); CA (1); ES (1); JP (1); US (3)