Metastatic Breast Cancer
Conditions
Keywords
PARP inhibitor, Drug Response Prediction (DRP), Tankyrase 1/2 inhibitor, mRNA biomarker
Brief summary
2X-121 is a small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells. The PARP inhibitor demonstrated clinical activity in a prior Phase 1 study in a number of solid tumors. 2X-121 has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2. The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome some of the PARP inhibitor resistance. The Phase 2 study is using 2x-121 DRP® biomarker in metastatic breast cancer patients to identify patients likely to respond to and benefit from treatment with 2X-121.
Interventions
DRUGPARP inhibitor 2X-121
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
Sponsors
Smerud Medical Research International AS
Danish Breast Cancer Cooperative Group
Allarity Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form. * Age 18 years or older. * Histologically or cytological documented mBC (independent of hormone receptor, HER2 status and BRCA1 or 2 status) relapsed in 2 or more different prior therapies. * Measurable disease by CT scan or MRI. * With a drug response prediction (DRP) for 2X-121 with an outcome measured as being in the upper 20% likelihood of response. * Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed. * Performance status of ECOG \<= 1 * Recovered to Grade 1 or less from prior surgery or from acute toxicities of prior radiotherapy, or from treatment with cytotoxic, hormonal or biologic agents). * \>= 2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF. * Patients with intracranial disease must be on stable or decreased level of steroid therapy (e.g. dexamethasone) for at least 7 days prior to baseline MRI. Non-enzymatic inducing ant-epileptic drugs are allowed. * Adequate conditions as evidenced by the following clinical laboratory values: * Absolute neutrophils count (ANC) \>= 1.5 x 10E9/L * Haemoglobin is at least 4.6 mmol/L * Platelets \>= 100 x 10E9 /L * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 2.5 x ULN\* * Serum bilirubin \<= 1.5 ULN * Alkaline phosphatase \<= 2.5 x ULN\* * Creatinine \<= 1.5 ULN * Blood urea within normal limits * Creatinine clearance within normal limits. \*In case of known liver metastases with ALT and AST \<= 5 x ULN and/or alkaline phosphatase \<= 5 x ULN. Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor. * Life expectancy equal or longer than 3 months. * Sexually active females of child-producing potential must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.
Exclusion criteria
* \- Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period. * Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study. * Previous treatment with PARP inhibitors * Any active infection requiring parenteral or oral antibiotic treatment. * Has known HIV positivity. * Has known active hepatitis B or C. * Has clinical significant (i.e. active) cardiovascular disease: * Stroke within \<= 6 months prior to day 1 * Transient ischemic attach (TIA) within \<= 6 months prior to day 1 * Myocardial infarction within \<= 6 months prior to day 1 * Unstable angina * New York Hart Association (NYHA) Grade II or greater congestive heart failure (CHF) * Serious cardiac arrhythmia requiring medication * Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy. * Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results * Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of 2X-121. * Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy. * Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumour efficacy after treatment with 600 mg 2X-121 as single oral agent in a 21-days cycle in mBC patients selected by the 2X-121 DRP | one year | Overall tumor response according to RECIST |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) after administration of 2X-121 in patients with mBC | one year | Timespan |
| Duration of objective response after administration of 2X-121 in patients with mBC | one year | Timespan |
| Overall survival (OS) after administration of 2X-121 in patients with mBC | one year | Timespan |
| Performance status (ECOG) | one year | To evaluate change in patient performance status by ECOG (Eastern Cooperative Oncology Group) Performance Status by a 6-step classification system |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | one year | Adverse Events as assessed by CTCAE v4. to evaluate safety profile after administration of 2X-121 in patients with mBC |
Countries
Denmark
Outcome results
None listed