Breast Cancer FemalePhase 3NCT05016349
Investigating the Potential Role of a Novel Quadrate Combination Therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic Acid and Cannabidiol ( Selective Cyp 26 Inhibitor) for Treating Early Breast Cancer.
A Phase 3 study testing All trans-retinoic acid, 13-Cis Retinoic Acid plus Tocopherol and Mifepristone in people with Breast Cancer Female, run by Mahmoud Ramadan mohamed Elkazzaz.
Trial summary
Investigating the potential role of a novel quadrate combination therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic acid and Cannabidiol ( selective cyp 26 inhibitor) for treating early breast cancer. Breast cancer is the main cause of mortality among women. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Breast Cancer Female
- What is being tested?
- All trans-retinoic acid, 13-Cis Retinoic Acid plus Tocopherol and Mifepristone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- No sites listed yet
- Study dates
- Aug 2021to Dec 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent
- Confirmed diagnosis of breast cancer positive at least for CEA tumor marker at above normal threshold level.
- e willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
- Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
- Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR
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- ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
- ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated per institutional standard.
Who cannot join
- Pregnant
- Treatment including radiation therapy, chemotherapy, biotherapy and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry.
- Any medical or other condition that in the Investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Gastrointestinal disorders that may interfere with absorption of the study drug.
- Co-existing active infection or serious concurrent illness
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- Current uncontrolled illness, for instance sepsis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- Current use of antiretroviral therapy
- Participants with psychiatric illness or social situations that would limit compliance with study requirements
- Current hepatocellular carcinoma, liver metastases, or documented history of difficult to control diabetes
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Why Antiprogestrone (Mifepristone) and Cyp 26 Inhibitor Must be Combined With Tamoxifen or ( Tamoxifen and Retinoic Acid) for Treating Early Breast Cancer
Investigating the potential role of a novel quadrate combination therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic acid and Cannabidiol ( selective cyp 26 inhibitor) for treating early breast cancer.
Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Therapy resistance remains a major problem in estrogen receptor-α (ERα)-positive breast cancer. Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. Here, we propose a testable hypothesis that treatment of breast cancer with tamoxifen or retinoic acid or a combination of the two, may result in induction or conversion of some ER-positive breast cancer cells to ER-negative cancer cells expressing the basal cytokeratin-5 (CK5) via stimulation of progesterone receptors effect, and production . Therefore, we raised an issue with the answer " Why Antiprogestrone such Mifepristone and cyp 26 inhibitors must be combined with Tamoxifen or its combination with retinoic acid in the era of oncology for treating early breast cancer" .In fact, limited evidence has indicated that induction of CK5+ cells in ERα+ breast cancer is a unique effect of progestin (Prg) but many studies have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. In case-cohort study of 405 incident breast cancer cases, elevated circulating progesterone levels were associated with a 16% increase in the risk of breast cancer. A study demonstrated that tamoxifen induced progesterone receptors (PGR) in short term treatment. Another study showed that High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. These CK5-positive cells are therapy resistant and have increased tumor-initiating potential. Also, previous work has shown that retinoic acid, a chemical that results from the body's natural breakdown of vitamin A, should act against these CK5+ cells, but clinical trials of retinoids against breast cancer have been largely unsuccessful .Therefore we suggest that combination of retinoiac acid and tamoxifen was unsucssecful in treating breast cancer owing its ability to induce progesterone receptors and production leading to increasing numbers of CK5-positive cells which are therapy resistant . Although retinoid fenretinide reduced the accumulation of CK5+ cells during estrogen depletion. A study investigated the effects of all-trans-RA (atRA) on progesterone production in immature rat GCs cultured without gonadotropin. demonstrated that atRA enhanced progesterone production by upregulating the levels of steroidogenic acute regulatory protein (StAR) and cytochrome P450scc (Cyp11a1). Here, we suggest that tamoxifen or its combination with retinoic acid must be combined with anti-progesterone (Mifepristone) to achieve treatment with significant effect against early breast cancer. Moreover, Numerous studies have shown that CYP2D6 variant carriers (around 50% CYP2D6 variant carriers in Chinese population) will not benefit a lot from tamoxifen, and combined use of CYP2D6 inhibitors will further affect the efficacy of tamoxifen. In addition, All-trans-retinoic acid acts as an inducer of CYP26A1 expression. Which is the second expected cause of unsuccessful trial of Tamoxifen and retinoic acid in breast cancer treatment. Furthermore, The CYP26 inhibitor also induced expression of atRA-responsive genes. All-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells. One study found that high retinol was significantly. associated with reduced breast cancer risk. Another found a significant trend of reduced retinol levels with more advanced disease stage. A study showed that intake of vitamin A and retinol could reduce breast cancer risk. Therefore we will take the benefit of cyp 26 inhibitor in this trial by combining Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6.
Read the detailed description
The study is a randomized interventional comparative Phase II trial. which will Investigating and test the safety and effectiveness of a Novel Quadrate Combination Therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic Acid and Cannabidiol ( Selective Cyp 26 Inhibitor) to learn whether this novel combination therapy works in treating Treating Early Breast Cancer. The primary objective of the study is to; 1) evaluate the anti-tumor activity of this combination therapy within the context of a phase II study Other objectives are: 2) to determine the effect of this novel combination therapy on cytokeratin 5 (CK5)-expressing cells;3) and to determine the expression of CK5 biomarkers of breast carcinogenesis before and after treatment.160 adult female patients with breast cancer and fulfilling the below outlined inclusion criteria will be enrolled into the study.
- Conditions
- Breast Cancer Female
- Being tested
- All trans-retinoic acid, 13-Cis Retinoic Acid plus Tocopherol, Mifepristone, Cannabidiol, 9 cis retinoic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
All trans-retinoic acidDrug
Also called Vesanoid
Vesanoid will be supplied orally at the total dosage of 45mg/m2/d (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days
13-Cis Retinoic Acid plus TocopherolDrug
13-Cis Retinoic Acid (50 mg/m2/d) Tocopherol (800 mg/day) supplied orally at the total dosage of 50 mg/m2/d (two daily administrations of 25 mg/m2 each). Treatment will last 28 days
MifepristoneDrug
Mifepristone 200mg capsules daily for 28 days
CannabidiolDrug
Also called Epidiolex
Liquid taken orally for daily for 28 days
9 cis retinoic acidDrug
9 cis retinoic acid will be supplied orally at the total dosage of 45mg/m2/d (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days
TamoxifenDrug
Patients will be given 10mg Tamoxifen twice a day. Treatment will last 28 days
Standard therapyDrug
Patients will receive the approved standard therapy tamoxifen
| Study group | Role | What they receive |
|---|---|---|
| All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral All trans-retinoic acid and Mifepristone daily for 2 weeks ,after which daily oral Cannabidiol (Epidiolex) is added to the regimen for 2 weeks , after which daily oral tamoxifen is added to the regimen. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: All trans-retinoic acid; Drug: Mifepristone; Drug: Cannabidiol; Drug: Tamoxifen |
| Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen | Experimental | Patients will receive oral Mifepristone daily for 4 weeks ,after which daily oral All trans-retinoic acid, tamoxifen and Cannabidiol (Epidiolex) is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: All trans-retinoic acid; Drug: Mifepristone; Drug: Cannabidiol; Drug: Tamoxifen |
| Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral Mifepristone, All trans-retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: All trans-retinoic acid; Drug: Mifepristone; Drug: Cannabidiol; Drug: Tamoxifen |
| 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral Mifepristone, 9 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: Mifepristone; Drug: Cannabidiol; Drug: 9 cis retinoic acid; Drug: Tamoxifen |
| Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral Mifepristone, 13 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: 13-Cis Retinoic Acid plus Tocopherol; Drug: Mifepristone; Drug: Cannabidiol; Drug: Tamoxifen |
| 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral 9 cis retinoic acid and Mifepristone daily for 2 weeks ,after which daily oral Cannabidiol (Epidiolex) is added to the regimen for 2 weeks , after which daily oral tamoxifen is added to the regimen. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: Mifepristone; Drug: Cannabidiol; Drug: 9 cis retinoic acid; Drug: Tamoxifen |
| 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Patients will receive oral Mifepristone, 13 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. Receives: Drug: 13-Cis Retinoic Acid plus Tocopherol; Drug: Mifepristone; Drug: Cannabidiol; Drug: Tamoxifen |
| Standard therapy | Sham comparator | Patients will receive the approved standard therapy Receives: Drug: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokeratin 5 (CK5)-expression
Cytokeratin 5 (CK5)-expression
Measured: Baseline to 4 weeks
To evaluate and compare the pathological complete response (pCR) rates
Measured: Up to 1 month after treatment
Secondary outcomes (4)
To evaluate the overall clinical response rate
Measured: Up to 1 month after treatment
Estradiol and progesterone levels in breast tissue and plasma assessed by liquid chromatography/tandem mass spectrometry
Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
Measured: Up to 1 month after treatment
Retinoic acid, TAM and their metabolites levels in breast tissue and plasma
Analysis will be pilot in nature and will provide descriptive statistics for each group or subgroup of subjects, supplying results which may be used to plan future studies.
Measured: Up to 1 month after treatment
Effect on level of serum tumor markers compared to baseline
Commonly measured tumor markers associated with breast cancer, primarily CA 15-3, CA 27.29, and CEA, at baseline and at study termination
Measured: Weekly for 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2021
- Study startAug 2021 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mahmoud Ramadan mohamed Elkazzaz
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Saudi Arabia
- Responsible party
- Sponsor-investigator, Mahmoud Ramadan mohamed Elkazzaz, Kafrelsheikh University
- Investigators
- Mahmoud Elkazzaz, Principal investigator, New Damietta University HospitalAmr Ahmed, Principal investigator, Ministry of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05016349
- Sponsor's protocol ID
- New theory(Tamoxifen&retinoic)
- Status last verified
- Aug 2021
- First submitted
- 17 Aug 2021
- Last updated
- 23 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Why Antiprogestrone (Mifepristone) and Cyp 26 Inhibitor Must be Combined With Tamoxifen or ( Tamoxifen and Retinoic Acid) for Treating Early Breast Cancer
- ClinicalTrials.gov ID
- NCT05016349
- Acronym / sponsor ID
- New theory(Tamoxifen&retinoic)
- Conditions
- Breast Cancer Female
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Mahmoud Ramadan mohamed ElkazzazUniversity, hospital or other
- Collaborators
- Ministry of Health, Saudi Arabia
- Study start
- Aug 2021 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 23 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigating the potential role of a novel quadrate combination therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic acid and Cannabidiol ( selective cyp 26 inhibitor) for treating early breast cancer.
Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Therapy resistance remains a major problem in estrogen receptor-α (ERα)-positive breast cancer. Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. Here, we propose a testable hypothesis that treatment of breast cancer with tamoxifen or retinoic acid or a combination of the two, may result in induction or conversion of some ER-positive breast cancer cells to ER-negative cancer cells expressing the basal cytokeratin-5 (CK5) via stimulation of progesterone receptors effect, and production . Therefore, we raised an issue with the answer " Why Antiprogestrone such Mifepristone and cyp 26 inhibitors must be combined with Tamoxifen or its combination with retinoic acid in the era of oncology for treating early breast cancer" .In fact, limited evidence has indicated that induction of CK5+ cells in ERα+ breast cancer is a unique effect of progestin (Prg) but many studies have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. In case-cohort study of 405 incident breast cancer cases, elevated circulating progesterone levels were associated with a 16% increase in the risk of breast cancer. A study demonstrated that tamoxifen induced progesterone receptors (PGR) in short term treatment. Another study showed that High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. These CK5-positive cells are therapy resistant and have increased tumor-initiating potential. Also, previous work has shown that retinoic acid, a chemical that results from the body's natural breakdown of vitamin A, should act against these CK5+ cells, but clinical trials of retinoids against breast cancer have been largely unsuccessful .Therefore we suggest that combination of retinoiac acid and tamoxifen was unsucssecful in treating breast cancer owing its ability to induce progesterone receptors and production leading to increasing numbers of CK5-positive cells which are therapy resistant . Although retinoid fenretinide reduced the accumulation of CK5+ cells during estrogen depletion. A study investigated the effects of all-trans-RA (atRA) on progesterone production in immature rat GCs cultured without gonadotropin. demonstrated that atRA enhanced progesterone production by upregulating the levels of steroidogenic acute regulatory protein (StAR) and cytochrome P450scc (Cyp11a1). Here, we suggest that tamoxifen or its combination with retinoic acid must be combined with anti-progesterone (Mifepristone) to achieve treatment with significant effect against early breast cancer. Moreover, Numerous studies have shown that CYP2D6 variant carriers (around 50% CYP2D6 variant carriers in Chinese population) will not benefit a lot from tamoxifen, and combined use of CYP2D6 inhibitors will further affect the efficacy of tamoxifen. In addition, All-trans-retinoic acid acts as an inducer of CYP26A1 expression. Which is the second expected cause of unsuccessful trial of Tamoxifen and retinoic acid in breast cancer treatment. Furthermore, The CYP26 inhibitor also induced expression of atRA-responsive genes. All-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells. One study found that high retinol was significantly. associated with reduced breast cancer risk. Another found a significant trend of reduced retinol levels with more advanced disease stage. A study showed that intake of vitamin A and retinol could reduce breast cancer risk. Therefore we will take the benefit of cyp 26 inhibitor in this trial by combining Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6.
Detailed description
The study is a randomized interventional comparative Phase II trial. which will Investigating and test the safety and effectiveness of a Novel Quadrate Combination Therapy Mifepristone(Antiprogestrone), Tamoxifen, Retinoic Acid and Cannabidiol ( Selective Cyp 26 Inhibitor) to learn whether this novel combination therapy works in treating Treating Early Breast Cancer. The primary objective of the study is to; 1) evaluate the anti-tumor activity of this combination therapy within the context of a phase II study Other objectives are: 2) to determine the effect of this novel combination therapy on cytokeratin 5 (CK5)-expressing cells;3) and to determine the expression of CK5 biomarkers of breast carcinogenesis before and after treatment.160 adult female patients with breast cancer and fulfilling the below outlined inclusion criteria will be enrolled into the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: All trans-retinoic acid, Drug: Mifepristone, Drug: Cannabidiol, Drug: TamoxifenPatients will receive oral All trans-retinoic acid and Mifepristone daily for 2 weeks ,after which daily oral Cannabidiol (Epidiolex) is added to the regimen for 2 weeks , after which daily oral tamoxifen is added to the regimen. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen | Experimental | Drug: All trans-retinoic acid, Drug: Mifepristone, Drug: Cannabidiol, Drug: TamoxifenPatients will receive oral Mifepristone daily for 4 weeks ,after which daily oral All trans-retinoic acid, tamoxifen and Cannabidiol (Epidiolex) is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: All trans-retinoic acid, Drug: Mifepristone, Drug: Cannabidiol, Drug: TamoxifenPatients will receive oral Mifepristone, All trans-retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: Mifepristone, Drug: Cannabidiol, Drug: 9 cis retinoic acid, Drug: TamoxifenPatients will receive oral Mifepristone, 9 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: 13-Cis Retinoic Acid plus Tocopherol, Drug: Mifepristone, Drug: Cannabidiol, Drug: TamoxifenPatients will receive oral Mifepristone, 13 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: Mifepristone, Drug: Cannabidiol, Drug: 9 cis retinoic acid, Drug: TamoxifenPatients will receive oral 9 cis retinoic acid and Mifepristone daily for 2 weeks ,after which daily oral Cannabidiol (Epidiolex) is added to the regimen for 2 weeks , after which daily oral tamoxifen is added to the regimen. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen | Experimental | Drug: 13-Cis Retinoic Acid plus Tocopherol, Drug: Mifepristone, Drug: Cannabidiol, Drug: TamoxifenPatients will receive oral Mifepristone, 13 cis retinoic acid and Cannabidiol (Epidiolex) daily for 4 weeks ,after which daily oral tamoxifen is added to the regimen , a. Patients continue treatment for up to 28 weeks, with tamoxifen continued after the study if medically appropriate. |
| Standard therapy | Sham comparator | Drug: Standard therapyPatients will receive the approved standard therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent
- Confirmed diagnosis of breast cancer positive at least for CEA tumor marker at above normal threshold level.
- e willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
- Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
Key exclusion criteria (10 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| All trans-retinoic acidAlso: VesanoidVesanoid will be supplied orally at the total dosage of 45mg/m2/d (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days | Drug | All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen |
| 13-Cis Retinoic Acid plus Tocopherol13-Cis Retinoic Acid (50 mg/m2/d) Tocopherol (800 mg/day) supplied orally at the total dosage of 50 mg/m2/d (two daily administrations of 25 mg/m2 each). Treatment will last 28 days | Drug | 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen |
| MifepristoneMifepristone 200mg capsules daily for 28 days | Drug | 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen |
| CannabidiolAlso: EpidiolexLiquid taken orally for daily for 28 days | Drug | 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen |
| 9 cis retinoic acid9 cis retinoic acid will be supplied orally at the total dosage of 45mg/m2/d (two daily administrations of 22.5 mg/m2 each). Treatment will last 28 days | Drug | 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen |
| TamoxifenPatients will be given 10mg Tamoxifen twice a day. Treatment will last 28 days | Drug | 13 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid , Mifepristone Cannabidiol (Epidiolex) and tamoxifen, 9 cis retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, All trans-retinoic acid, Mifepristone Cannabidiol (Epidiolex) and tamoxifen, Mifepristone , All trans-retinoic acid, Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, 13 cis retinoic acid , Cannabidiol (Epidiolex) and tamoxifen, Mifepristone, Cannabidiol (Epidiolex) , All trans-retinoic acid and tamoxifen |
| Standard therapyPatients will receive the approved standard therapy tamoxifen | Drug | Standard therapy |
Primary outcome
Cytokeratin 5 (CK5)-expression
Time frame: Baseline to 4 weeks
Cytokeratin 5 (CK5)-expression
To evaluate and compare the pathological complete response (pCR) rates
Time frame: Up to 1 month after treatment
4 secondary outcomes
To evaluate the overall clinical response rate
Time frame: Up to 1 month after treatment
Estradiol and progesterone levels in breast tissue and plasma assessed by liquid chromatography/tandem mass spectrometry
Time frame: Up to 1 month after treatment
Retinoic acid, TAM and their metabolites levels in breast tissue and plasma
Time frame: Up to 1 month after treatment
Effect on level of serum tumor markers compared to baseline
Time frame: Weekly for 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mahmoud Elkazzaz principal investigator
New Damietta University Hospital
Amr Ahmed principal investigator
Ministry of Health
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing All trans-retinoic acid, 13-Cis Retinoic Acid plus Tocopherol and Mifepristone in people with Breast Cancer Female, run by Mahmoud Ramadan mohamed Elkazzaz.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mahmoud Elkazzaz (00201090302015, mahmoudramadan2051@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytokeratin 5 (CK5)-expression (time frame: Baseline to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.