| CTRI Number |
CTRI/2009/091/000057 [Registered on: 11/02/2009] |
| Last Modified On: |
15/03/2013 |
| Post Graduate Thesis |
|
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Other |
Public Title of Study
Modification(s)
|
A Clinical study to evaluate the effect of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin in Comparison With Paclitaxel and Carboplatin in Anaplastic Thyroid Carcinoma patients. |
Scientific Title of Study
Modification(s)
|
A Multicenter, Open-Label, Randomized, Phase II/III Study to Evaluate the Safety and Efficacy of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin in Comparison With Paclitaxel and Carboplatin Against Anaplastic Thyroid Carcinoma |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| NCT00507429 |
ClinicalTrials.gov |
| OXC4T4-302 |
Other |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr C S Bal |
| Designation |
|
| Affiliation |
|
| Address |
All India Institute of Medical Sciences Department of Nuclear Medicine Therapy,
Room Number 57AIIMS, Ansari Nagar, Delhi 110029
New Delhi
DELHI
110029
India |
| Phone |
09868397182 |
| Fax |
01126588993 |
| Email |
csbal@hotmail.com |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Rajesh Gaikwad |
| Designation |
|
| Affiliation |
Project Manager |
| Address |
DiagnoSearch Life Sciences Pvt. Ltd.
Unit No. 702, 7th Floor,
Dosti Pinnacle,
Plot No. E7, Road No. 22,
Wagle Industrial Estate,
Thane
MAHARASHTRA
400 604
India |
| Phone |
02267776357 |
| Fax |
02266754090 |
| Email |
rajesh.gaikwad@diagnosearch.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Rajesh Gaikwad |
| Designation |
|
| Affiliation |
Project Manager |
| Address |
DiagnoSearch Life Sciences Pvt. Ltd.
Unit No. 702, 7th Floor,
Dosti Pinnacle,
Plot No. E7, Road No. 22,
Wagle Industrial Estate,
Thane
MAHARASHTRA
400 604
India |
| Phone |
02267776357 |
| Fax |
02266754090 |
| Email |
rajesh.gaikwad@diagnosearch.com |
|
Source of Monetary or Material Support
Modification(s)
|
|
Primary Sponsor
Modification(s)
|
| Name |
Oxigene Inc |
| Address |
230, 3rd Avenue, 6th floor
Waltham
MA 02451
USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| Oxigene Inc USA |
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Kirti Sardana |
All India Institute of Medical Sciences |
Department of Nuclear Medicine Therapy, Room Number 57AIIMS,,Ansari Nagar , New Delhi,-110029
New Delhi
DELHI |
09958218110
01126588993
kirti.sardana@gmail.com |
| Tanvira Rahman |
Apollo Cancer Institute |
Spectra Clinical Research Centre ,Indraprastha Apollo Hospital,Sarita Vihar,Delhi Mathura Road,-110076
New Delhi
DELHI |
09810729747
01141677024
rahmantanvira@gmail.com |
| Naveen Kumar |
Christian Medical College |
Ida Ferdder Road, ,-632004
Vellore
TAMIL NADU |
09894587624
04164203200
naveenkumarcmc@yahoo.com |
| Dr. Praveenkumar |
Kidwai Hospital |
Dr.M.H.Marigowda Road,,-560029
Bangalore
KARNATAKA |
09480339895
0806565671
drpraveenkumar7912@hotmail.com |
| Jagadeesh Babu |
Mediciti Hospital, |
5-9-22, Secriatriat road, ,-500063
Hyderabad
ANDHRA PRADESH |
09959143386
04023299078
email: jagamediciti@gmail.com |
| Dr. Yogita Kasture |
Ruby Hall Clinic |
Ruby Hall Clinic, 40,sasson Road, -411001
Pune
MAHARASHTRA |
09823216529
02066455603
yogi8283@gmail.com |
| Dr. Raghavendra |
Shirdi Sai Baba Cancer Hospital Katsurba Medical College & Hospital Manipal |
Department of Radiotherapy and Oncology,,Shirdi Sai Baba Cancer Hospital Katsurba Medical College & Hospital Manipal,-576104
|
09986297732
0820-2571999
drraghavendra@ecronacunova.com |
| Dr. Anjana Shrivastava |
Tata Memorial Hospital |
Dr.E. Borges Road,Parel, ,-400012
Mumbai
MAHARASHTRA |
09820401867
02224171734
anjanashri@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Ethics Committe - AIIMS, Delhi |
Approved |
| Ethics Committee - Mediciti Hospitals, Hyderabad |
Approved |
| Ethics Committee - Poona Medical Research Foundation, Pune |
Approved |
| Ethics Committee on clinical trials,Indraprastha Apollo Hospital,Delhi |
Approved |
| Human Ethics Committee - Tata Memorial Hospital, Mumbai |
Approved |
| Institutional Review Board - Christian Medical College, Vellore |
Submittted/Under Review |
| Medical Ethics Committee - Kidwai Memorial Institute of oncology , Bangalore |
Approved |
| University Ethics Committee - Manipal University, Manipal |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Anaplastic Thyroid Carcinoma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Drug: carboplatin |
6 AUC on Day 1 following paclitaxel |
| Intervention |
Drug: combretastatin A-4 phosphate (CA4P) |
CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles |
| Comparator Agent |
Drug: paclitaxel |
200mg/m squared on Day 1 |
|
|
Inclusion Criteria
|
| Age From |
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| Age To |
|
| Gender |
|
| Details |
Inclusion Criteria:
I1. Subjects must have anaplastic thyroid carcinoma histologically or cytologically confirmed by a pathology review.
o A mixture of ATC with another type of thyroid malignancy is admissible.
o Review will be performed by a preselected local pathologist with expertise in endocrine malignancies.
I2. Subjects may have received prior chemotherapy as a component of combined modality therapy at time of diagnosis, but not subsequently for metastatic disease.
o Subjects are eligible if they have progressed or relapsed during or following initial combined modality therapy for regionally advanced disease.
o Subjects are eligible if they had metastatic disease at the time of commencement or during initial combined modality therapy. In this case, systemic therapy is limited to one chemotherapy regimen that is clearly administered contiguously, (i.e., in an uninterrupted primary therapeutic approach).
o Subjects who receive chemotherapy for metastatic disease after completing prior combined modality approach are ineligible.
o Subjects may have received prior chemotherapy as a component of combined modality therapy at time of diagnosis, but not subsequently.
I3. A minimum of 3 weeks must have elapsed from completion of radiation therapy until first dose of study drug.
I4. A minimum of 3 weeks must have elapsed from the time a subject last received chemotherapy until the first dose of study drug (6 weeks for therapy known to be associated with delayed toxicity such as nitrosureas or mitomycin-C).
I5. Subjects must have no clinically important sequelae from any prior surgery or radiotherapy.
I6. Subjects with bulky thyroid/neck masses and/or suspicion of airway obstruction must undergo screening (indirect or direct laryngoscopy) to ensure patency of the trachea/airway prior to study enrollment and treatment.
o Subjects with a tracheostomy are eligible.
I7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Score  2.
I8. Life expectancy ≥ 12 weeks.
I9. Subjects must have adequate bone marrow reserve as evidenced by:
o Absolute neutrophil count (ANC) > 1,500/L (without growth factors).
o Platelet count > 100,000/L
I10. Subjects must have adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL ( 177 mol/L).
I11. Subjects must have adequate hepatic function as evidenced by:
o Serum total bilirubin 2X greater than the upper limit of normal (ULN) (3X ULN in subjects with liver metastases).
o AST (aspartate aminotransferase)/ALT (alanine aminotransferase) 3X the ULN for the local reference lab (5X the ULN for subjects with liver metastases).
I12. Subjects must be at least 18 years old.
I13. Subjects or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
I14. All women of childbearing potential must have a negative serum pregnancy test. (Women who are ≥2 years post-menopausal, post-hysterectomy or have had a surgical sterilization do not require pregnancy test.)
I15. Women of childbearing potential as well as fertile men and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication. (An effective form of contraception is an oral contraceptive or a double barrier method.)
|
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| ExclusionCriteria |
| Details |
E1. Subjects with tumors confined to the thyroid.
E2. Subjects with a uncontrolled, clinically significant active infection
E3. Clinically active brain metastasis, including symptomatic involvement, evidence of cerebral edema by prior CT or MRI, radiographic evidence of progression of brain metastasis since definitive therapy, or continued requirement for corticosteroids for cerebral edema.
E4. Subjects who receive chemotherapy for metastatic ATC after completion of a combined modality approach.
E5. Subjects with history of malignancies other than ATC except: 1) preceeding lower grade thyroid malignancy; 2) curatively treated basal cell carcinoma of the skin; 3) curatively treated cervical intra-epithelial neoplasia; 4) curatively treated localized prostate cancer with a current PSA of < 4.0 mg/dL or μg/L. (Subjects with other curatively treated malignancies who have no evidence of metastatic disease will be considered after discussion with the Medical Monitor.)
E6. Subjects with known intolerance of or hypersensitivity to CA4P or required premedications, or known uncontrolled hypersensitivity to paclitaxel, or carboplatin or CT contrast dye, or any of their components.
E7. Subjects who are receiving concurrent investigational therapy or who have received investigational therapy for any indication within 28 days of the first scheduled day of dosing. (Investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication.)
E8. Subjects with ≥Grade 3 peripheral neuropathy.
E9. Subjects who are pregnant or lactating.
E10. Subjects with a history of prior cerebrovascular event, including transient ischemic attack.
E11. Subjects with uncontrolled hypertension defined as blood pressure > 150/100 mm Hg despite medication.
E12. Subjects with symptomatic vascular disease (e.g., intermittent claudication).
E13. Subjects with a history of unstable angina pectoris pattern, myocardial infarction (including non-Q wave MI) within the past 6 months, or NYHA Class III and IV congestive heart failure.
E14. Subjects with a history of torsade de pointes, ventricular tachycardia, ventricular fibrillation or congenital long QT syndrome.
E15. Subjects with bradycardia (<60 b/m) or heart block (excluding 1st degree block, consisting of PR interval prolongation only).
E16. Subjects with ECG findings of clinically significant ventricular arrhythmia, new ST segment elevation or depression, or new Q wave on ECG. (PVCs are not excluded)
E17. Subjects with QTc > 450 ms for males and >470 ms for females.
E18. Subjects requiring on-going treatment with any drugs known to prolong the QTc interval, including anti-arrhythmic medications (see APPENDIX 5 for list of medications).
E19. Subjects with ejection fractions less than normal (i.e. <45%) on echocardiogram.
E20. Subjects with potassium concentrations below 4.0 mEq/L (or mmol/L), magnesium concentrations below 1.8 mmol/L
o Supplements may be used to increase electrolyte levels
E21. Subjects with a history of solid organ transplant or bone marrow transplant.
E22. Subjects with any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject?s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
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Method of Generating Random Sequence
|
Stratified block randomization |
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Method of Concealment
|
|
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Blinding/Masking
|
Open Label |
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Primary Outcome
|
| Outcome |
TimePoints |
| Primary outcome: To compare the antineoplastic efficacy of CA4P +paclitaxel+carboplatin versus paclitaxel+carboplatin against ATC by measuring overall survival |
One year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Secondary outcome: To evaluate the safety and tolerability of the triple combination of CA4P+paclitaxel+carboplatin To assess specified objective events: tracheostomies, PEG tube placements, and weight loss To determine percentage of one year survival To determine the clinical benefit, as measured by Progression Free Survival (PFS) |
one year |
|
Target Sample Size
Modification(s)
|
Total Sample Size="180"
Sample Size from India="60"
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 2/ Phase 3 |
|
Date of First Enrollment (India)
|
Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/08/2007 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
|
Publication Details
|
|
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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
|
This is a multicenter, open-label, 2:1 randomized, study of CA4P administered in combination with paclitaxel and carboplatin compared with paclitaxel and carboplatin administered alone.
Approximately 180 subjects will be recruited from approximately 50 multinational sites of which up to an estimated 17 sites will be located in the United States. It is estimated that overall subject accrual will occur over approximately 18 months.
Primary Objective:
To compare the antineoplastic efficacy of CA4P +paclitaxel+carboplatin versus paclitaxel+carboplatin against ATC by measuring overall survival
Secondary Objective:
To evaluate the safety and tolerability of the triple combination of CA4P+paclitaxel+carboplatin
To assess specified objective events: tracheostomies, PEG tube placements, and weight loss
To determine percentage of one year survival
To determine the clinical benefit, as measured by Progression Free Survival (PFS)
|