Advanced Refractory Solid TumorsPhase 1NCT01779336
Clinical Study of Oral IGF-1R Inhibitor in Subjects With Advanced Refractory Solid Tumors
A Phase 1 study testing PL225B in people with Advanced Refractory Solid Tumors, run by Piramal Enterprises Limited at 5 sites in 2 countries.
Trial summary
Clinical study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity (ies) of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Advanced Refractory Solid Tumors
- What is being tested?
- PL225B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Dec 2012to Dec 2014
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative or palliative treatment does not exist or is no longer effective
- Subjects should have measurable or evaluable disease
- Subjects of either sex, of all races and ethnic groups, and ≥18 years of age
- ECOG (Eastern Cooperative Oncology Group) performance status 0-1
- Subjects with life expectancy of at least 4 months
- Subjects with fasting plasma glucose ≤ 125 mg/dL and HbA1c < 6.5 % at screening Subjects with fasting plasma glucose ≤150 mg/dL and HbA1c ≤ 7.0 % at screening for the Diabetes Expansion Cohort.
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- For the Diabetes Expansion Cohort - Subjects with known history of type 2 diabetes mellitus that are well-controlled on a stable dose of oral anti-diabetic agents such as metformin and/or sulfonylureas for 4 weeks prior to screening.
- Subjects must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1500/cmm
- Platelets ≥ 100,000/cmm
- Total bilirubinwithin normal limits of the institution
- AST/ALT ≤ 2.5 X institutional upper limit of normal (ULN) or ≤ 5 X institutional upper limit of normal (ULN) in the presence of liver metastases
- Creatinine ≤ 1.5 X institutional upper limit of normal (ULN)
- Subjects willing for repeat oral dosing and follow-up, including pharmacokinetic sampling
- Women of childbearing potential and men willing to agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised
- Ability to understand and the willingness to provide a written informed consent document
Who cannot join
- Subjects who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before the first study drug administration and have not recovered (to AEs < Grade 2) from the toxic effects from any prior therapy
- Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs < Grade 2) from the side effects of the earlier investigational agent
- Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort
- For the Diabetes Expansion Cohort - Subjects who have type 1 diabetes mellitus, maturity onset diabetes of the young, hyperglycemia due to reasons other than type 2 diabetes mellitus.
- For the Diabetes Expansion Cohort - Subjects who currently require insulin, thiazolidinediones, dual proliferator-activated receptors (PPAR) agonists, glucagon-like peptide (GLP-1) analogues, dipeptidyl peptidase (DPP-IV) inhibitors or have received the same in the 4 weeks prior to screening.
- Subjects with known complications of diabetes like diabetic nephropathy or diabetic retinopathy
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- Subjects with known brain metastases
- Subjects with gastrointestinal abnormalities including inability to take oral medication, malabsorption or other conditions like chronic inflammatory bowel disease that may affect absorption.
- Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months
- Subjects with baseline QTc interval >470 msec at screening
- Subjects on warfarin. Prophylactic anticoagulation with low molecular weight heparin is allowed
- Subjects with history of anaphylaxis or angioedema, bronchial asthma, peptic ulcer and clinically significant food or drug allergy
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Women who are pregnant or nursing
- Subjects with known seropositivity to human immunodeficiency virus (HIV), positive for Hepatitis B, positive for Hepatitis C (antigen positive), or known hepatic cirrhosis
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
India4 sites
Meenakshi Mission Hospital and Research Centre
Madurai, Tamil Nadu, 625107
Central India Cancer Research Institute
Nagpur, Maharashtra, 440010
Curie Manavata Cancer Centre
Nashik, Maharashtra, 422004
Ruby Hall Clinic
Pune, Maharashtra, 411001
United States1 site
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
About this study
Official title: An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.
Clinical study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity (ies) of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors.
Read the detailed description
An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. This is a dose-finding trial using the modified Accelerated Titration Design with 3 new subjects per cohort and 100% dose increments in the accelerated phase followed by standard phase with 40% dose increments.Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy. Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD) according to the schedule given below.
- Conditions
- Advanced Refractory Solid Tumors
- Being tested
- PL225B
- Keywords
- Advanced Refractory Solid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PL225BDrug
- Patients will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.
- This 21 day administration will define a treatment cycle.
- Patients may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified.
| Study group | Role | What they receive |
|---|---|---|
| PL225B | Experimental | Patients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design. Receives: Drug: PL225B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD).
Measured: End of Cycle 1 (i.e. 21 Days)
Secondary outcomes (4)
Number of subject with adverse events
The toxic effects of the drug would be assessed from adverse events, vital signs and by clinically significant changes in the laboratory evaluations.
Measured: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Pharmacokinetic profile(Cmax,Tmax and AUC)
The following PK parameters will be calculated: Cmax (peak plasma concentration), Tmax (time to peak plasma concentration), AUC0-t (area under the plasma concentration curve from time zero to time of last quantifiable concentration), AUC0-12, AUC0-inf (area under the plasma concentration curve from time zero extrapolated to infinity), percent AUC extrapolated, kel (elimination rate constant), t1/2 (elimination half-life), CL/F (oral clearance), Vz/F (oral apparent volume of distribution) and Racc (accumulation ratio).
Measured: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Activity of PL225B based on selected biomarkers
Plasma samples will be used for analysis of circulating exploratory biomarkers which are likely to change in response to PL225B administration.
Measured: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Objective response
Evaluation of Response: Clinical responses will be presented patient wise for different dose levels.
Measured: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2013 (estimated)
- Study startDec 2012
- Primary completionNov 2014 (estimated)
- Study completionDec 2014 (estimated)
Why it stopped: Sponsor decision not related to patient safety
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Refractory Solid TumorsStudies of the same condition, open and under way.
- 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
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Piramal Enterprises Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr Anthony El-Khoueiry, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01779336
- Sponsor's protocol ID
- PL225B/71/11
- Status last verified
- Sep 2014
- First submitted
- 28 Jan 2013
- Last updated
- 29 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.
- ClinicalTrials.gov ID
- NCT01779336
- Acronym / sponsor ID
- PL225B/71/11
- Conditions
- Advanced Refractory Solid Tumors
- Keywords
- Advanced Refractory Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Sponsor decision not related to patient safety
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Piramal Enterprises LimitedIndustry (pharma, biotech, devices)
- Study start
- Dec 2012
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 30 Jan 2013 (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.
Clinical study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity (ies) of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors.
Detailed description
An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors. This is a dose-finding trial using the modified Accelerated Titration Design with 3 new subjects per cohort and 100% dose increments in the accelerated phase followed by standard phase with 40% dose increments.Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy. Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD) according to the schedule given below.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PL225B | Experimental | Drug: PL225BPatients will receive study drug on a daily basis until disease progression or unacceptable toxicity in sequential cohorts following accelerated titration design. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Subjects having histologically and/or cytologically confirmed non-haematological malignancy that is metastatic or unresectable and for which standard curative or palliative treatment does not exist or is no longer effective
- Subjects should have measurable or evaluable disease
- Subjects of either sex, of all races and ethnic groups, and ≥18 years of age
- ECOG (Eastern Cooperative Oncology Group) performance status 0-1
- Subjects with life expectancy of at least 4 months
Key exclusion criteria (15 listed)
- Subjects who have received any prior chemotherapy, radiotherapy, biologic/targeted anti-cancer therapy or surgery within 4 weeks (6 weeks for monoclonal antibodies, radioactive monoclonal antibodies or any radio- or toxin- immunoconjugates) before the first study drug administration and have not recovered (to AEs < Grade 2) from the toxic effects from any prior therapy
- Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs < Grade 2) from the side effects of the earlier investigational agent
- Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort
- For the Diabetes Expansion Cohort - Subjects who have type 1 diabetes mellitus, maturity onset diabetes of the young, hyperglycemia due to reasons other than type 2 diabetes mellitus.
- For the Diabetes Expansion Cohort - Subjects who currently require insulin, thiazolidinediones, dual proliferator-activated receptors (PPAR) agonists, glucagon-like peptide (GLP-1) analogues, dipeptidyl peptidase (DPP-IV) inhibitors or have received the same in the 4 weeks prior to screening.
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 |
|---|---|---|
| PL225B* Patients will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy. * This 21 day administration will define a treatment cycle. * Patients may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified. | Drug | PL225B |
Primary outcome
Maximum tolerated dose
Time frame: End of Cycle 1 (i.e. 21 Days)
Subjects will receive study drug on a daily basis for twenty-one (21) days according to the dose and schedule specified for a particular cohort of therapy.Toxicity profile of the drug will be assessed during Cycle 1 of subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD).
4 secondary outcomes
Number of subject with adverse events
Time frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Pharmacokinetic profile(Cmax,Tmax and AUC)
Time frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Activity of PL225B based on selected biomarkers
Time frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Objective response
Time frame: Until disease progression or unacceptable toxicity (expected to be 4-6 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2014.
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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.
Dr Anthony El-Khoueiry, MD principal investigator
University of Southern California
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PL225B in people with Advanced Refractory Solid Tumors, run by Piramal Enterprises Limited at 5 sites in 2 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 16 inclusion and 15 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: paused, as of the sponsor's last update on 29 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in India, United States. 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?
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?
Maximum tolerated dose (time frame: End of Cycle 1 (i.e. 21 Days)). 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 29 Sep 2014.