| CTRI Number |
CTRI/2012/12/003208 [Registered on: 12/12/2012] Trial Registered Prospectively |
| Last Modified On: |
02/09/2014 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A clinical trial to Study PL225B in Subjects with Advanced Refractory Solid Tumors |
|
Scientific Title of Study
|
An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects with Advanced Refractory Solid Tumors |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| PL225B/71/11 Version 1.0 (09-Mar-2012) |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Minish Jain |
| Designation |
Consultant Medical Oncologist |
| Affiliation |
Ruby Hall Clinic |
| Address |
Ruby Hall Clinic, 40 Sassoon Road, Pune 411001
Pune
MAHARASHTRA
411001
India |
| Phone |
02066455604 |
| Fax |
|
| Email |
minishjain009@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sandesh Sawant |
| Designation |
Assistant Clinical Leader |
| Affiliation |
Piramal Enterprises Limited |
| Address |
Piramal Enterprises Limited
Nirlon Complex,
Off Western Express Highway
Goregaon (East), Mumbai, Maharashtra
India
Mumbai (Suburban)
MAHARASHTRA
400063
India |
| Phone |
02230275130 |
| Fax |
|
| Email |
sandesh.sawant@piramal.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sanjeev C Hegde |
| Designation |
General Manager |
| Affiliation |
Piramal Enterprises Limited |
| Address |
Piramal Enterprises Limited
Nirlon Complex,
Off Western Express Highway
Goregaon (East), Mumbai, Maharashtra
India
Mumbai (Suburban)
MAHARASHTRA
400063
India |
| Phone |
02230275011 |
| Fax |
|
| Email |
sanjeev.hegde@piramal.com |
|
|
Source of Monetary or Material Support
|
| Sponsor-Piramal Enterprises Limited |
|
|
Primary Sponsor
|
| Name |
Piramal Enterprises Limited |
| Address |
Nirlon Complex,
Off Western Express Highway
Goregaon (East),Mumbai-400063, Maharashtra
India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ajay Mehta |
Central India Cancer Research Institute |
Central India Cancer Research Institute, 11, Shankar Nagar, West High Court Road, Nagpur - 440 010
Nagpur
MAHARASHTRA |
91-712-2520956
91-712-2521503
ajayonco@hotmail.com |
| Dr Rajnish Nagarkar |
Curie Manavata Cancer Centre |
O.P.D.
Department of Surgical oncology, Opp.Mahamarga Bus
Stand, Mumbai Naka,
Nasik-422004
Nashik
MAHARASHTRA |
02532592666
drraj@manavatacancercentre.com |
| Dr Krishna Kumar Ratnam |
Meenakshi Mission Hospital and Research Centre |
Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road, Madurai - 625 107
Madurai
TAMIL NADU |
91-9380417299
91-452-2586353
kkratnam@gmail.com |
| Dr Minish Jain |
Ruby Hall Clinic |
Room No. 302, 3rd Floor,
Cancer Building,40-Sassoon Road, Pune 411 001
Pune
MAHARASHTRA |
02066455604
minishjain009@gmail.com |
| Dr Kumar Prabhash |
Tata Memorial Centre |
Department of Medical Oncology, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Sector No.22,Kharghar, Navi Mumbai -410210
Mumbai
MAHARASHTRA |
9224182898
kprabhash1@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Central India Cancer Research Institute Ethics Committee |
Approved |
| Ethics Committee-Advanced Centre for Treatment, Research and Education in Cancer |
Submittted/Under Review |
| Institutional Ethics Committee |
Approved |
| Manavta Clinical Research Institute, Professional Ethics committee |
Approved |
| Poona Medical Research Foundation |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Advanced refractory solid tumors, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
NIL |
NIL |
| Intervention |
PL225B |
Study drug will be administered once daily for 21 days. PL225B will be administered orally in the form of tablet(s) once daily. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
1. 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
2. Subjects should have measurable or evaluable disease
3. Subjects of either sex, of all races and ethnic groups, and more than equal to 18 years of age
4. ECOG (Eastern Cooperative Oncology Group) performance status 0-1
5. Subjects with life expectancy of at least 4 months
6. Subjects with fasting plasma glucose less than equal to 125 mg/dl and HbA1c less than 6.5 % at screening Subjects with fasting plasma glucose less than equal to 150 mg/dL and HbA1c less than equal to 7.0 % at screening for the Diabetes Expansion Cohort
7. 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.
8. Subjects willing for repeat oral dosing and follow-up, including pharmacokinetic sampling
9. 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
10. Ability to understand and the willingness to provide a written informed consent document
|
|
| ExclusionCriteria |
| Details |
1. 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 less than equal to Grade 2) from the toxic effects from any prior therapy
2. Subjects having received any other investigational agents within 4 weeks prior to the first study drug administration and have not recovered completely (to AEs less than equal to Grade 2) from the side effects of the earlier investigational agent
3. Subjects with documented history of diabetes mellitus except for the Diabetes Expansion Cohort
4. 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
5. 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
6. Subjects with known complications of diabetes like diabetic nephropathy or diabetic retinopathy
7. Subjects with known brain metastases
8. Subjects with gastro intestinal abnormalities including inability to take oral medication, malabsorption or other conditions like chronic inflammatory bowel disease that may affect absorption
9. Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months
10. Subjects on warfarin. Prophylactic anticoagulation with low molecular weight heparin is allowed.
11. Subjects with history of anaphylaxis or angio-edema, bronchial asthma, peptic ulcer and clinically significant food or drug allergy
12. Subjects with uncontrolled inter-current 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
13. Women who are pregnant or nursing
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To determine the maximum tolerated dose and dose limiting toxicity (ies). |
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. This 21 day administration will define a treatment cycle. Subjects may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. To characterize the safety profile of PL225B
2. To characterize the pharmacokinetic profile of PL225B
3. To evaluate activity of PL225B based on effect on selected biomarkers
4. To evaluate efficacy of PL225B based on objective response
5. To evaluate the safety, tolerability, pharmacokinetics and efficacy of PL225B in subjects of advanced refractory solid tumors with type 2 diabetes mellitus in a Diabetes Expansion Cohort
|
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. This 21 day administration will define a treatment cycle. Subjects may receive consecutive treatment cycles until evidence of disease progression, intolerance of therapy, or withdrawal from the protocol as specified |
|
|
Target Sample Size
|
Total Sample Size="70"
Sample Size from India="70"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
31/12/2012 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Suspended |
| Recruitment Status of Trial (India) |
Suspended |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with advanced refractory solid tumors to determine the maximum tolerated dose and dose limiting toxicity (ies) and also to evaluate the safety, tolerability, pharmacokinetics and efficacy of PL225B in subjects of advanced refractory solid tumors with type 2 diabetes mellitus in a Diabetes Expansion Cohort |