| CTRI Number |
CTRI/2025/01/079432 [Registered on: 24/01/2025] Trial Registered Prospectively |
| Last Modified On: |
24/01/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Comparison of Oral Metronomic therapy (OMT) versus treatment of physicians choice(TPC) chemotherapy in platinum resistant advanced ovarian cancer. |
|
Scientific Title of Study
|
Oral Metronomic therapy (OMT) versus treatment of physicians choice(TPC) chemotherapy in platinum resistant advanced ovarian cancer: a randomized controlled study |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Raja Pramanik |
| Designation |
Additional Professor |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Room No. 160F, Dr. BRA-IRCH,AIIMS
AIIMS, Ansari Nagar
New Delhi
DELHI
110049
India |
| Phone |
09654976088 |
| Fax |
|
| Email |
drrajapramanik@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Raja Pramanik |
| Designation |
Additional Professor |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Room No. 160F, Dr. BRA-IRCH,AIIMS
AIIMS, Ansari Nagar
DELHI
110049
India |
| Phone |
09654976088 |
| Fax |
|
| Email |
drrajapramanik@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Raja Pramanik |
| Designation |
Additional Professor |
| Affiliation |
AIIMS, NEW DELHI |
| Address |
Room No. 160F, Dr. BRA-IRCH,AIIMS
AIIMS, Ansari Nagar
DELHI
110049
India |
| Phone |
09654976088 |
| Fax |
|
| Email |
drrajapramanik@gmail.com |
|
|
Source of Monetary or Material Support
|
| Department of Biotechnology
Ministry of Science and technology, government of India
4th-5th Floor, Block 3 CGO Complex, Lodhi Road New Delhi 110 003.India |
|
|
Primary Sponsor
|
| Name |
Department of Biotechnology |
| Address |
Ministry of Science and Technology
4th-5th Floor, Block 3 CGO Complex, Lodhi Road New Delhi 110 003.India |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Raja Pramanik |
AIIMS, New Delhi |
Room No. 160F,
Department of Medical Oncology,
1st floor, Dr.BRA-IRCH,
AIIMS, New Delhi
South
DELHI |
9654976088
drrajapramanik@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| INSTITUTE ETHICS COMMITTEE, AIIMS, NEW DELHI |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Oral Metronomic therapy- OMT
Etoposide, Cyclophosphamide,and Pazopanib |
The intervention group will receive 3 drugs OMT:
Tab etoposide (50 mg, day 1 to 10,
Tab cyclophosphamide (50 mg, day 1 to 28),
and
Tab Pazopanib (400 mg once daily)
every 4 weeks till progression of disease. |
| Comparator Agent |
Treatment of Physicians Choice (TPC) |
Patients in this arm will receive single-agent chemotherapy of physicians choice. This will include single-agent paclitaxel (80mg/m2 D1, D8, D15, q 28 days),
or
single-agent Topotecan (4 mg/m2 IV on days 1, 8, and 15 every 4 weeks)
or
single agent Liposomal doxorubicin (40mg/m2, q 28 days). |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
85.00 Year(s) |
| Gender |
Female |
| Details |
1. Histologically confirmed recurrent or metastatic epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer of high-grade serous or endometrioid histology.
2. Patients must have platinum resistant disease (defined as progression within 6 months from completion of a minimum of 4 cycles of platinum containing chemotherapy.
3. Patients must have progressed on or after their most recent line of therapy. Progression must be determined radiographically (RECIST 1.1) and/or CA125 GCIG progression criteria.
4. Participants who had received one line of platinum-based therapy must have received at least four cycles of their initial platinum-containing regimen, had a response (complete or partial), and then had disease progression between 3 and 6 months after their last dose.
5. Patients who have previously received two or three lines of platinum-based therapy must have had disease progression while receiving the therapy or within 6 months after the last dose. Progression will be calculated from the date of the last administered dose of platinum-based therapy to the date of radiographic imaging that shows evidence of progression. Adjuvant± Neoadjuvant and maintenance is considered 1 line of therapy, therapy changed due to toxicity in the absence of progression will be considered part of same line, hormonal therapy will be counted as a separate line unless given in maintenance.
6. Patient must have at least one lesion that meets the definition of measurable disease by RECIST 1.1.
7. Age 18 years to 85 years
8. ECOG PS 0 to 2
9. Written informed consent
10. Registered in the Gynecologic Medical Oncology Clinic at AIIMS, New Delhi, or in NCI-AIIMS, Jhajjar
|
|
| ExclusionCriteria |
| Details |
1. Patients who have refractory disease (progression during the previous platinum-containing therapy) will be ineligible.
2. Patients with clinical symptoms of bowel obstruction.
3. Surgery within 4 weeks before starting study therapy or anticipated need for major surgery during study treatment.
4. Current or recent treatment with another investigational drug within 30 days before the first study dose.
5. Untreated CNS disease or symptomatic CNS metastasis.
6. Serious concurrent illness or clinically relevant active infections.
7. Patients assigned to PLD stratum only. LVEF below the institutional limit of normal as measured by echocardiography.
8. Pregnant or lactating
9. Patients with clear-cell, mucinous or sarcomatous histology, low grade or borderline disease.
|
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| median progression free survival |
3 years |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| median overall survival |
median overall survival |
| overall response rate |
after 4 months of intervention |
| quality of life |
At 0,4,6 months |
|
|
Target Sample Size
|
Total Sample Size="280"
Sample Size from India="280"
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 3 |
|
Date of First Enrollment (India)
|
01/03/2025 |
| 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="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Advanced
epithelial ovarian cancer has dismal outcomes. Worst is the case with “Platinum
refractory disease” (PROC), those relapsing within 6 months of platinum-based
chemotherapy, with poor response to further chemotherapy and a median survival
of<1 year. The current standard of care for PROC is single-agent
non-platinum-based chemotherapy. Previous research from our institute showed
that the 3-drug combination (Pazopanib+ Cyclophosphamide+Etoposide) could be a
novel oral metronomic therapy (OMT) for PROC. [PMID :32048620,34088513].
Our proposal is the next obvious step, to compare this OMT with
standard IV chemotherapy in a randomized study. If found superior, OMT will be
a new line of therapy, an extremely affordable and acceptable option. This will be a randomized phase-III, superiority
trial, with a parallel design and 1:1 randomization. Patients, with platinum-resistant ovarian cancers will be randomized to the two arms i.e, the Standard of care arm ( IV chemotherapy of physician’s choice which can be either of weekly Paclitaxel, liposomal doxorubicin or weekly Irionotecan) and the Intervention Arm (Oral Metronomic chemotherapy comprising of 3 drugs : Tab Pazopanib 400mg daily, Tab Cyclophosphamide 50mg D1-D28, Cap Etoposide 50mg D1-D10. Our primary objective is to compare the median progression-free
survival ( mPFS) on the OMT arm
(experimental arm) versus IV chemotherapy of physician choice (standard of care
arm) for the intent-to-treat (ITT) population. Our Secondary objectives are a) To compare the median overall
survival (mOS) on the OMT arm (experimental arm) versus IV chemotherapy
(standard of care arm) for the ITT population, b) To compare the objective response
rates (ORR) for the two arms of the study at 4 months, c)To compare the Quality of life in the
two arms at baseline, 4 months, and 6 months using EORTC QLQ-C30/OV28. With a power of 80%, 1 sided Type-I error
of 0.05 to detect a hazard ratio of 0.7 for median progression-free survival,
assuming an mPFS of 3.4 months in the TPC arm and 5.0 months in the OMT arm, and
assumed attrition of 2%, we would need 207 events among 276 patients. We,
therefore, plan to randomize 280 patients, 140 in each arm.
|