| CTRI Number |
CTRI/2022/12/048015 [Registered on: 12/12/2022] Trial Registered Prospectively |
| Last Modified On: |
19/09/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Phase 1 clinical trial on Cancer patients |
|
Scientific Title of Study
|
A phase 1, open label study to evaluate MTD, safety, tolerability and pharmacokinetics of oral drug AB001 in patients with various types of metastatic cancer patients. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| AB001/CT/2022 Ver 01 dated 14.09.2022 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr M G Dinesh |
| Designation |
Additional Director |
| Affiliation |
Vopec Pharmaceuticals Private Limited |
| Address |
B-13, Mogappair Industrial Estate,
Mogappair West,
Chennai, Tamilnadu,
India
Chennai
TAMIL NADU
600037
India |
| Phone |
9600007573 |
| Fax |
|
| Email |
rnd@vopecpharma.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr M G Dinesh |
| Designation |
Additional Director |
| Affiliation |
Vopec Pharmaceuticals Private Limited |
| Address |
B-13, Mogappair Industrial Estate,
Mogappair West,
Chennai, Tamilnadu,
India
TAMIL NADU
600037
India |
| Phone |
9600007573 |
| Fax |
|
| Email |
rnd@vopecpharma.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr M G Dinesh |
| Designation |
Additional Director |
| Affiliation |
Vopec Pharmaceuticals Private Limited |
| Address |
B-13, Mogappair Industrial Estate,
Mogappair West,
Chennai, Tamilnadu,
India
TAMIL NADU
600037
India |
| Phone |
9600007573 |
| Fax |
|
| Email |
rnd@vopecpharma.com |
|
|
Source of Monetary or Material Support
|
| Vopec Pharmaceuticals Private Limited B-13, Mogappair Industrial Estate,
Mogappair West,
Chennai, Tamilnadu,
India - 600037
|
|
|
Primary Sponsor
|
| Name |
Vopec Pharmaceuticals Private Limited |
| Address |
B-13, Mogappair Industrial Estate, Mogappair West, Chennai, Tamilnadu, India - 600037 |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrSuresh Kumar |
Erode Cancer center |
Department of Oncology
Velavan Nagar
Perundurai Raod Thindal Erode Tamil nadu 638012
Erode
TAMIL NADU |
04242910700
sureshonco@gmail.com |
| DrAnita Ramesh |
Saveetha Medical College and Hospital |
Departmnet of Oncology Saveetha Nagar,
Thandalam,
Chennai
Chennai
TAMIL NADU |
04466726618
anitachandra100@hotmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| IEC- Erode Cancer center |
Approved |
| IEC-Saveetha Medical College and Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C910||Acute lymphoblastic leukemia [ALL], (2) ICD-10 Condition: C920||Acute myeloblastic leukemia, (3) ICD-10 Condition: C7A0||Malignant carcinoid tumors, (4) ICD-10 Condition: C259||Malignant neoplasm of pancreas, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 100 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 200 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 40 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 400 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 500 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Intervention |
AB001-(1E,4E,6E)-1-(3,5- dimethoxyphenyl)-7-(4- ydroxy3,5-
dimethoxyphenyl)hepta1,4,6- trien-3-one
|
Dose 800 mg
Route of administration: Orally
Frequency : BID
Duration: 14 days
|
| Comparator Agent |
NIL |
NIL |
|
|
Inclusion Criteria
|
| Age From |
20.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Willing and able to provide voluntary informed consent and able to comply with protocol requirements.
2. Age – 20 to 65 years.
3. Patients with advanced Cancer not amenable to surgical therapy.
4. Patients must have measurable disease on radiological imaging of CT / MRI / PET scan to monitor treatment response. Measurable disease, as defined by RECIST v1.1.
5. Patients Undergoing is allowed to take part in the study.
6. Women of child bearing potential must agree to either use a contraceptive method or to remain abstinent during the treatment period and for at least 3 months after the last dose of study drug.
7. Life expectancy > 24 weeks.
8. Patient should be willing to undergo all treatment related procedures and investigations.
9. Patient should be willing and ready for PET scan, Blood Investigations, PK, ECG and followup.
10. Patient is willing to take and to tolerate cytotoxic drugs.
11. No history of addiction to any recreational drug or drug dependence.
12. Non-smokers and non-alcoholics. |
|
| ExclusionCriteria |
| Details |
1. Patients above 65 years of age.
2. Pregnant or lactating women, or intending to become pregnant during the study.
3. Life threatening comorbidities such as HIV, HPV, HBV, HCV, Tuberculosis, CHF, Impaired Hepatic or Renal Function or any psychological deficits etc.
4. Known CNS disease (Alzheimer’s disease, Parkinson’s disease, Bell’s palsy, Cerebral Palsy, Epilepsy, Motor Neuron disease (MND), Multiple Sclerosis (MS), Neurofibromatosis. Sciatica and Shingles) except for treated asymptomatic CNS metastases.
5. Uncontrolled pleural effusion, pericardial effusion, or as cites.
6. Uncontrolled tumor-related pain.
7. Significant cardiovascular disease, such as New York Heart Association of classification (NYHA) cardiac disease (Class II or greater), MI within 3 months prior to randomization, unstable arrhythmias, or unstable angina.
8. Major surgical procedure within 4 weeks prior to randomization or anticipation of the need for a major surgical procedure during the study other than for diagnosis.
9. History of autoimmune disease.
10. Prior allogeneic stem cell or solid organ transplantation.
11. Poor peripheral venous access.
12. Any other medical condition or uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.) that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
13. Patients not suitable for study as per investigators opinion
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To assess the safety and toxicity profile of AB001 in patients with metastasis cancer using the NCI CTCAE V4.03, and determine the maximum tolerated dose (MTD).
1. To determine the maximum tolerated dose (MTD) of AB001.
2. To determine the dose limiting toxicities (DLT) of AB001.
3. To establish a safe dose level of AB001 that can be used for future studies.
|
Day 0 to Day 14 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1. The pharmacokinetics of AB001 in humans.
2. Observe for evidence of antitumor activity following administration of AB001.
3. If AB001 induces changes in the biomarker in peripheral blood lymphocytes.
4. If there is a pharmacodynamic relationship between the plasma / blood concentrations of AB001 and a clinical or cellular effect.
5. To monitor the tumor reduction & adverse events and to ensure the safety of patients
|
Day 0 to Day 14
Safety follow up evaluation : on 21st day |
|
|
Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "33"
Final Enrollment numbers achieved (India)="33" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
12/12/2022 |
| Date of Study Completion (India) |
13/07/2023 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="1"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The identified lead
AB001 demonstrated a good solubility and an acceptable in vivo PK profile. The
identified AB001 showed an in
vivo efficacy in mouse triple-negative breast cancer, Acute myeloid leukemia
model, Pancreatic cancer model with a TGI (tumor growth inhibition) of 90% without
any mortality growth inhibition in comparison to reported leads. Our results
show that AB001 is widely scattered across different organs, but it is
preferentially internalized by the tumor both in vitro and in vivo. AB001
administration showed a potent in vivo anticancer activity in xenograft mouse
models, and the drug accumulated dramatically and preferentially in the tumor.
The follow-up studies for 12 months shows there is no relapse of tumor growth
in the internal organs. We demonstrate
the effectiveness of AB001 in resensitizing Multiple Drug Resistance breast cancer cells to their original treatment and
provide evidence that AB001 may function through a mechanism involving
post-translational histone modifications via an indirect histone deacetylase
inhibitor (HDACi) activity and selectively target cancer stem cells and induces
apoptosis via caspase activity. According to the results, further well-designed
clinical studies with dose optimization
are now required to stratify the role of this supplement in current Breast
Cancer regimens. Our data, together with the apoptotic action of the AB001 on
cancer cells, support a rather selective action of AB001 in cancer treatment.
According to the results, further well-designed clinical studies with dose optimization are now required to
stratify the role of this supplement in current Cancer regimens |