Locally Advanced Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
RP6530, Tenalisib
Brief summary
Phase II, randomized, open-label study, designed to evaluate the preliminary efficacy and safety of tenalisib at two dose levels in 40 patients with locally advanced or metastatic breast cancer.
Detailed description
The study will have two groups, Group 1 with a treatment option of 800mg RP6530 BID and Group 2 with a treatment option of 1200mg RP6530 BID, where the subjects will be randomly assigned to each group in 1:1 and continued on each group of treatment till disease progressed.
Interventions
DRUGTenalisib 800mg
Tenalisib will be administered 800mg BID, orally
DRUGTenalisib 1200mg
Tenalisib will be administered 1200mg BID, orally
Sponsors
Rhizen Pharmaceuticals SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must be ≥18 years of age, at the time of signing informed consent. 2. Female patients who have histologically and/or cytologically confirmed locally advanced or metastatic breast cancer that has progressed following at least one line of therapy. 3. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that can be accurately assessed by CT scan or MRI and is suitable for repeated assessment at follow up-visits. 4. ECOG performance status 0 to 2. 5. Life expectancy of at least 3 months. 6. Adequate bone marrow, liver, and renal functions 7. Female patients of childbearing potential should be willing to use a medically acceptable method of contraception
Exclusion criteria
1. Patients with HER-2 positive breast cancer. 2. Patients receiving anticancer therapy within 4 weeks or 5 half-lives of the drug prior to C1D1, whichever is shorter. 3. Patient who has not recovered from acute toxicities (defined as NCI-CTCAE grade \> 1) of previous therapy except treatment-related alopecia. 4. Patients who have had disease progression within 8 weeks of platinum chemotherapy. 5. Prior exposure to investigational or marketed PI3K inhibitors given for the treatment of breast cancer. 6. Major surgery within 4 weeks of starting study treatment OR any patient who has not recovered from the effects of major surgery. 7. Patient with symptomatic uncontrolled brain metastasis. 8. HIV-positive patients who are on antiretroviral therapy OR active hepatitis C OR active hepatitis B virus infections. 9. Ongoing immunosuppressive therapy including systemic corticosteroids except as allowed per concomitant medication. 10. Known history of severe liver injury as judged by the investigator. 11. History of severe cutaneous reactions in the past. 12. Active gastrointestinal tract disease with malabsorption syndrome or uncontrolled inflammatory gastrointestinal disease such as Crohn's disease or ulcerative colitis. 13. Pregnancy or lactation. 14. Patient with other active malignancies at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Without Disease Progression | Approximately 6 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Approximately 18 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
| Clinical Benefit Rate (CBR) | Approximately 18 months | It is defined as sum of CR, PR and SD rates |
| Progression Free Survival (PFS). | Approximately 18 months | PFS is measured from the time of first dose of study drug to radiographic documentation of disease progression or death due to any cause. |
| Treatment Emergent Adverse Events (TEAEs) | Approximately 18 months | Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not related to the investigational product. |
Countries
Georgia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tenalisib 800 mg BID Tenalisib: Tenalisib will be administered 800mg BID, orally | 20 |
| Tenalisib 1200 mg BID Tenalisib: Tenalisib will be administered 1200mg BID, orally | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Tenalisib 800 mg BID | Total | Tenalisib 1200 mg BID |
|---|---|---|---|
| Age, Continuous | 61.27 years | 63.18 years | 64.21 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 39 Participants | 19 Participants |
| Region of Enrollment Georgia | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 20 | 1 / 20 |
| other Total, other adverse events | 15 / 20 | 17 / 20 |
| serious Total, serious adverse events | 5 / 20 | 1 / 20 |
Outcome results
Primary
Percentage of Patients Without Disease Progression
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenalisib 800 mg BID | Percentage of Patients Without Disease Progression | 7 Participants |
| Tenalisib 1200 mg BID | Percentage of Patients Without Disease Progression | 8 Participants |
Secondary
Clinical Benefit Rate (CBR)
It is defined as sum of CR, PR and SD rates
Time frame: Approximately 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenalisib 800 mg BID | Clinical Benefit Rate (CBR) | 11 Participants |
| Tenalisib 1200 mg BID | Clinical Benefit Rate (CBR) | 12 Participants |
Secondary
Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Approximately 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenalisib 800 mg BID | Overall Response Rate (ORR) | 2 Participants |
| Tenalisib 1200 mg BID | Overall Response Rate (ORR) | 3 Participants |
Secondary
Progression Free Survival (PFS).
PFS is measured from the time of first dose of study drug to radiographic documentation of disease progression or death due to any cause.
Time frame: Approximately 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenalisib 800 mg BID | Progression Free Survival (PFS). | 170 days |
| Tenalisib 1200 mg BID | Progression Free Survival (PFS). | 170 days |
Secondary
Treatment Emergent Adverse Events (TEAEs)
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not related to the investigational product.
Time frame: Approximately 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tenalisib 800 mg BID | Treatment Emergent Adverse Events (TEAEs) | 15 Participants |
| Tenalisib 1200 mg BID | Treatment Emergent Adverse Events (TEAEs) | 17 Participants |