| CTRI Number |
CTRI/2010/091/001144 [Registered on: 05/08/2010] |
| Last Modified On: |
30/03/2013 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
Type of Study
Modification(s)
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Drug |
| Study Design |
Other |
Public Title of Study
Modification(s)
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This is an early phase clinical trial where the main aim is to determine the highest dose level of the study drug, E7389 that can be given together (in combination) with a chemotherapeutic drug, carboplatin, in patients with solid tumors. |
Scientific Title of Study
Modification(s)
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A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination with Carboplatin in Patients with Solid Tumors |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
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| Secondary ID |
Identifier |
| 2009-017977-40 |
EudraCT |
| E7389-A001-104 |
Protocol Number |
| NCT00268905 |
ClinicalTrials.gov |
| U1111-1116-2809 |
UTN |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr Rajat Hazra |
| Designation |
Sr. Manager - Project Manager |
| Affiliation |
|
| Address |
7th Floor, Tower D, Unitech Cyber Park, Sector-39
Gurgaon
HARYANA
122001
India |
| Phone |
|
| Fax |
|
| Email |
rhazra@clinirx.com |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Rajat Hazra |
| Designation |
|
| Affiliation |
Manager-Medical Affairs |
| Address |
CliniRx Research
Link House, 4th Floor,
3, Bahadur Shah Zafar Marg,
New Delhi 110 002
Central
DELHI
122001
India |
| Phone |
|
| Fax |
|
| Email |
rhazra@clinirx.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Dr Rajat Hazra |
| Designation |
|
| Affiliation |
|
| Address |
7th Floor, Tower D, Unitech Cyber Park, Sector-39
Gurgaon
HARYANA
122001
India |
| Phone |
91-9999769131 |
| Fax |
91124-4104203 |
| Email |
rhazra@clinirx.com |
|
Source of Monetary or Material Support
Modification(s)
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| Eisai Ltd. Mosquito Way, Hatfield, Hertfordshire AL10 9SN, United Kingdom
Eisai Inc., 300 Tice Boulevard, Woodcliff Lake, NJ 07677, USA
|
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Primary Sponsor
Modification(s)
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| Name |
Eisai Ltd |
| Address |
Eisai Ltd. Mosquito Way, Hatfield, Hertfordshire AL10 9SN, United Kingdom Eisai Inc., 300 Tice Boulevard, Woodcliff Lake, NJ 07677, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
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| Name |
Address |
| CliniRx Research |
CliniRx Research
Link House, 4th Floor,
3, Bahadur Shah Zafar Marg,
New Delhi – 110 002 (India)
Tele : +91 11 3300 1112
Fax : +91 11 2371 6607
|
|
Countries of Recruitment
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India |
Sites of Study
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| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr. Mamillapli Gopichand |
City Cancer Centre |
33-25-33, Ch. Venkata Krishnayya Street, Suryaraopet, ,-
|
91-866-2432180 / 91-866-2436661
91-866-2430871
mgopichand@yahoo.com |
| Dr. Kirushna Kumar |
Meenakshi Mission Hospital and Research Center |
Lake area Melur Road , ,-
Madurai
TAMIL NADU |
91-452-2588741
91-452-4219030
drkskk@yahoo.com |
| Dr. Minish Jain |
Ruby Hall Clinic |
40, Sassoon Road,-
Pune
MAHARASHTRA |
91-20-26123391 / 91-20-66455604
91-20-26124529
minishjain@gmail.com |
| Dr Shyam aggrawal |
Sir Ganga Ram Hospital |
Rajinder Nagar,-110060
New Delhi
DELHI |
91-11-25750000
91-11-25861002
drshyam_aggarwal@yahoo.com |
|
Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Ethical Review Board |
Approved |
| Poona Medical Research Foundation |
Approved |
| Radix Central Ethics Committee |
Approved |
| Sir Ganga Ram Hospital |
Approved |
|
Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
Patients with Solid Tumors, |
|
Intervention / Comparator Agent
Modification(s)
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| Type |
Name |
Details |
| Intervention |
E7389 |
E7389 will be administered in the NSCLC extension part of the study as a 2-5 minute intravenous bolus infusion on days 1 and 8 of a 21 day cycle at the starting dose of 1.1 mg/m2. Carboplatin will be administered at AUC 6 on day 1 as a 30-minute intravenous infusion after the administration of the E7389. The dose of E7389 will be escalalated to 1.4 mg/m2 if no DLTs are reported in the first six patients of the NSCLC extension part of the study. |
| Comparator Agent |
NA |
NA |
|
|
Inclusion Criteria
|
| Age From |
|
| Age To |
|
| Gender |
|
| Details |
1. Patients  18 years of age
2. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
3. Patients with a life expectancy of  three months
4. Patients with adequate renal function as evidenced by serum creatinine  2.0 mg/dL or calculated creatinine clearance  40 mL/min per the Cockcroft and Gault formula20
5. Patients with adequate bone marrow function as evidenced by absolute neutrophil count (ANC)  1.5  109/L, hemoglobin  10.0 g/dL (this may have been corrected by transfusion or growth factors) and platelet count  100  109/L
6. Patients with adequate liver function as evidenced by bilirubin  1.5 mg/dL and alkaline phosphatase, alanine transaminase (ALT) and AST  3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
7. Patients willing and able to comply with the study protocol for the duration of the study
8. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice
Patients in the Dose Finding Phase
For patients in the dose finding phase, the following additional inclusion criteria must be fulfilled:
1. Patients with pathologically diagnosed, histologically or cytologically confirmed advanced solid tumor, that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy)
2. Patients with disease progression despite standard therapy or have disease for which no standard therapy exists
3. Patients with  Grade 2 chemotherapy or radiation-related toxicities except alopecia
NSCLC Patients
For NSCLC patients in the extension study, the following additional inclusion criteria must be fulfilled:
1. Patients with pathologically diagnosed, histologically or cytologically confirmed advanced NSCLC (Stage IIIB or IV) with measurable disease, not amenable to surgical or radiation treatment
2. Patients with no prior chemotherapy for NSCLC including neoadjuvant or adjuvant treatment
|
|
| ExclusionCriteria |
| Details |
1. Patients are excluded if they have received any of the following within three weeks prior to first study treatment: investigational drugs, immunotherapy, gene therapy, hormone therapy (except leuprolide, and megestrol acetate for appetite stimulation), other biological therapy, chemotherapy or radiation. Patients with major surgery without full recovery or major surgery within 3 weeks prior to first study treatment are also excluded. Patients must have recovered from any previous major therapy-related toxicity (Grade 3 or 4) to < Grade 2 at study entry (except for neuropathy).
2. Patients who have received radiation ≤ 3 weeks prior to study enrollment, whose marrow exposure has exceeded 30% or who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia)
3. Patients who have received prior high dose chemotherapy with hematopoietic stem cell rescue or stem cell or bone marrow transplant in the past two years
4. Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
5. Patients with active symptomatic brain metastases. Patients with central nervous system (CNS) metastases are considered eligible if they have had adequately treated brain metastases, ie, have completed treatment (tapered off steroids) at least four weeks before starting treatment with E7389. Patients who have no evidence that the metastases are symptomatic or actively growing (no evidence of midline shift on CT scan or MRI) may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. It is not the intention of this study to treat patients with active brain metastases (revised per Amendment 01).
6. Patients with meningeal carcinomatosis
7. Patients who require therapeutic anti-coagulant therapy with warfarin or related compounds
8. Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the investigator (eg, using 2 forms of contraception including a barrier method) (revised per Amendment 01). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
9. Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception
10. Patients with severe/uncontrolled intercurrent illness or infection
11. Patients with significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)
12. Patients with organ allografts
13. Patients who have a history of positive testing for HIV and/or have active hepatitis B or active hepatitis C at study entry
14. Patients with pre-existing neuropathy > Grade 2
15. Patients with a hypersensitivity to halichondrin B and/or to a halichondrin B chemical derivative
16. Patients who participated in a prior E7389 clinical trial
17. Patients with other significant disease or disorders that, in the investigator?s opinion, would exclude the patient from the study
For NSCLC patients in the extension study, the following additional exclusion criterion must be fulfilled:
1. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated  five years previously with no subsequent evidence of recurrence
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|
Method of Generating Random Sequence
Modification(s)
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Not Applicable |
Method of Concealment
Modification(s)
|
Not Applicable |
Blinding/Masking
Modification(s)
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Not Applicable |
Primary Outcome
Modification(s)
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| Outcome |
TimePoints |
| To determine the maximum tolerated dose of E7389 in combination with carboplatin in patients with advanced solid tumors |
Event based analysis as per protocol specified standards |
|
Secondary Outcome
Modification(s)
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| Outcome |
TimePoints |
| To determine the pharmacokinetic profile of E7389 in combination with carboplatin |
Pharmacokinetic samplings (blood and urine) would be done on Cycle 1 Days 1, 2 and 3 only (dose escalation stages only) |
| To explore the safety of E7389 in combination with carboplatin .
To explore the anti-tumor activity of E7389 in combination with carboplatin in advanced solid tumors during the dose finding phase, and to evaluate the efficacy of E7389 at the MTD in combination with carboplatin in patients with stage IIIB or IV NSCLC not amenable to surgical or radiation treatment who have had no prior chemotherapy for disease by determining the following endpoints:
Best overall objective tumor response rate as defined by the RECIST criteria; Overall survival; Progression free survival; Duration of response .
|
Safety and efficacy evaluation will be done during the entire study at protocol specified time points.
Event based evaluation at protocol specified time points and final analysis at the end of the study. |
|
Target Sample Size
Modification(s)
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Total Sample Size="85"
Sample Size from India="10"
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
Modification(s)
|
Phase 1/ Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
01/10/2006 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years=""
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
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Publication Details
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|
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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Chemotherapy can increase survival and alleviate symptoms in patients with non-small cell lung cancer [NSCLC]. A meta-analysis that compared platinum- and non-platinum based regimens in more than 7,500 patients with NSCLC participating in 37 trials provides support for the use of platinum-containing chemotherapy as response rates are significantly improved with these agents. Combination regimens with platinum-based therapy is the standard of care for advanced NSCLC and good performance status. Each combination, however, is characterized by a unique adverse event profile, some prohibitive for the elderly or poor performance status patients due to its toxicities. Docetaxel, a tubulin-stabilizing taxane, has shown single agent activity as second-line therapy in paclitaxel- and platinum-pretreated NSCLC patients. The median and 1-year survival rates in patients treated with second-line docetaxel were superior to those achieved with best supportive care, and were achieved in conjunction with a positive impact on Quality of Life [QOL]. These data support the use of a tubulin-active agent with a platinum agent as doublet chemotherapy as an important therapeutic option. However, there is a clear need to develop doublet chemotherapy that will minimize toxicities while maintaining or improving survival and QOL. E7389, a novel microtubule modulator, has previously shown evidence of single agent activity in patients with advanced NSCLC in a Phase II study conducted in the USA. The hypothesis to be tested in this clinical trial is to see whether the study drug, E7389, can be administered in combination with platinum-based chemotherapy, carboplatin, and at what dose level. Once the doses of E7389 and carboplatin that can be co-administered has been determined, patients with advanced NSCLC who are not amenable to surgical or radiation treatment and who has received no prior chemotherapy for the NSCLC, including neoadjuvant or adjuvant treatment, will be recruited to evaluate the safety and preliminary anti-tumor efficacy of this combination. The primary objective for this Phase Ib study is therefore to determine the maximum tolerated dose [MTD] of the study drug, E7389, that can be administered in combination with carboplatin in patients with advanced solid tumors. This part of the study has been conducted in the USA only. The secondary objectives of this study are to explore the safety of E7389 in combination with carboplatin; explore the anti-tumor activity of E7389 in combination with carboplatin in advanced solid tumors during the dose finding phase; evaluate the efficacy of E7389 at the MTD in combination with carboplatin in patients with advanced (stage IIIB or IV) NSCLC not amenable to surgical or radiation treatment who have had no prior chemotherapy for disease (this part of the study is being conducted in India, Austria and the USA) and determine the pharmacokinetic profile of E7389 in combination with carboplatin. 72 patients (52 patients with solid tumors have been enrolled for the dose-finding part of this study and a total of 20 patients will be enrolled in the NSCLC extension part of the study). The study is currently active and enrolling in the USA, and three patients have been enrolled in the NSCLC extension part of the study as of 21 July 2010, of which one patient is ongoing in the study. India and Austria are participating in the NSCLC extension part of the study only. Up to 10 patients will be enrolled in India and recruitment is expected to begin in second week of August 2010. Regulatory approval has been received for Austria, and EC approval is currently pending in Austria. Recruitment in Austria will begin once EC approval has been granted. |