Investigation of Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP
- Registration Number
- NCT03562832
- Lead Sponsor
- Allarity Therapeutics
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
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Signed informed consent form.
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Age 18 years or older.
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Histologically or cytological documented mBC (independent of hormone receptor, HER2 status and BRCA1 or 2 status) relapsed in 2 or more different prior therapies.
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Measurable disease by CT scan or MRI.
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With a drug response prediction (DRP) for 2X-121 with an outcome measured as being in the upper 20% likelihood of response.
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Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed.
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Performance status of ECOG <= 1
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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).
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>= 2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
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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.
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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.
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Life expectancy equal or longer than 3 months.
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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.
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- Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.
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Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study.
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Previous treatment with PARP inhibitors
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Any active infection requiring parenteral or oral antibiotic treatment.
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Has known HIV positivity.
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Has known active hepatitis B or C.
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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
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Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
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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
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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.
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Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
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Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PARP inhibitor 2X-121 PARP inhibitor 2X-121 600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
Trial Locations
- Locations (2)
Vejle Sygehus
🇩🇰Vejle, Denmark
Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev
🇩🇰Herlev, Denmark