Advanced Solid TumorPhase 1NCT02189174
Study of CLR457 Administered Orally in Adult Patients With Advanced Solid Malignancies
A Phase 1 study testing CLR457 in people with Advanced Solid Tumor, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- CLR457
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 7 Aug 2014to 12 Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States3 sites
Massachusetts General Hospital SC-9
Boston, Massachusetts, 02114
Tennessee Oncology SC
Nashville, Tennessee, 37203
Memorial Sloan Kettering SC-4
New York, New York, 10017
About this study
Official title: A Phase I/II Multicenter, Open-label Study of CLR457, Administered Orally in Adult Patients With Advanced Solid Malignancies
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
- Being tested
- CLR457
- Keywords
- Solid tumor,, breast cancer,, lung cancer,, endometrial cancer
- Medical subject headings
- Breast Neoplasms, Lung Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLR457Drug
| Study group | Role | What they receive |
|---|---|---|
| CLR457 | Experimental | Not described Receives: Drug: CLR457 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLT
Measured: First 28 days of dosing
Objective response rate (ORR) as per RECIST v1.1
Measured: 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)
Measured: Continously throughout the study until 30 days after treatment discontinuation
Severity of AEs and SAEs and dose reductions and interruptions
Measured: Continously throughout the study until 30 days after treatment discontinuation
Duration of response (DOR)
per RECIST v1.1
Measured: Baseline, every 8 weeks until discontinuation for an expected average of 4 months
Progression free survival (PFS)
per RECIST v1.1
Measured: Baseline, every 8 weeks until discontinuation for an expected average of 4 months
Best overall response (BOR)
per RECIST v1.1
Measured: Baseline and every 8 weeks for an expected average of 4 months
Plasma concentration and Pharmacokinetics (PK) parameters of CLR457
Parameters including but not limited to Cmax, Cmin, AUCinf, AUCtlast, AUCtau and T1/2
Measured: 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
Changes from baseline in glucose metabolism markers (fasting glucose and insulin)
Measured: 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
Measured: Baseline, C2D1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2014 (estimated)
- Study start7 Aug 2014
- Primary completion12 Nov 2015
- Study completion12 Nov 2015
Why it stopped: Novartis decided to terminate the study considering safety and tolerability concerns and limited clinical activity with CLR457 study drug administered once daily (qd).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02189174
- Sponsor's protocol ID
- CCLR457X2101
- Status last verified
- Dec 2021
- First submitted
- 7 Jul 2014
- Last updated
- 3 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multicenter, Open-label Study of CLR457, Administered Orally in Adult Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT02189174
- Acronym / sponsor ID
- CCLR457X2101
- Conditions
- Advanced Solid Tumor
- Keywords
- Solid tumor,, breast cancer,, lung cancer,, endometrial cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Novartis decided to terminate the study considering safety and tolerability concerns and limited clinical activity with CLR457 study drug administered once daily (qd).
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2014 (actual)
- Primary completion
- 12 Nov 2015 (actual)
- Study completion
- 12 Nov 2015 (actual)
- First posted
- 14 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CLR457 | Experimental | Drug: CLR457 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (21 listed)
- Brain metastasis unless treated and neurologically stable
- Patient having out of range laboratory values defined as:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLR457 | Drug | CLR457 |
Primary outcome
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
8 secondary outcomes
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
Progression free survival (PFS)
Time frame: Baseline, every 8 weeks until discontinuation for an expected average of 4 months
Best overall response (BOR)
Time frame: Baseline and every 8 weeks for an expected average of 4 months
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
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
Results and safety
The study was stopped early (reason given: Novartis decided to terminate the study considering safety and tolerability concerns and limited clinical activity with CLR457 study drug administered once daily (qd).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CLR457 in people with Advanced Solid Tumor, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada, Japan, Singapore, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Novartis decided to terminate the study considering safety and tolerability concerns and limited clinical activity with CLR457 study drug administered once daily (qd).). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLT (time frame: First 28 days of dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2021.