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

Metastatic Breast Cancer Clinical Trial

Official title:

Phase II, Open Label Clinical Study to Investigate Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03562832
• Other study ID #: OV-121
• Secondary ID: SMR-3475
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 20, 2018
• Est. completion date: May 2024

Study information

• Verified date: July 2023
• Source: Allarity Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: May 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• PARP inhibitor 2X-121
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients

Locations

Country	Name	City	State
Denmark	Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev	Herlev
Denmark	Vejle Sygehus	Vejle

Sponsors (3)

Lead Sponsor	Collaborator
Allarity Therapeutics	Danish Breast Cancer Cooperative Group, Smerud Medical Research International AS

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall tumor response according to RECIST	one year
Secondary	Progression free survival (PFS) after administration of 2X-121 in patients with mBC	Timespan	one year
Secondary	Duration of objective response after administration of 2X-121 in patients with mBC	Timespan	one year
Secondary	Overall survival (OS) after administration of 2X-121 in patients with mBC	Timespan	one year
Secondary	Performance status (ECOG)	To evaluate change in patient performance status by ECOG (Eastern Cooperative Oncology Group) Performance Status by a 6-step classification system	one year
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse Events as assessed by CTCAE v4. to evaluate safety profile after administration of 2X-121 in patients with mBC	one year

External Links

•   Official Homepage of Sponsor