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
Primary Purpose
Metastatic Breast Cancer
Status
Active
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
PARP inhibitor 2X-121
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring PARP inhibitor, Drug Response Prediction (DRP), Tankyrase 1/2 inhibitor, mRNA biomarker
Eligibility Criteria
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)
Sites / Locations
- Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev
- Vejle Sygehus
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PARP inhibitor 2X-121
Arm Description
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Progression free survival (PFS) after administration of 2X-121 in patients with mBC
Timespan
Duration of objective response after administration of 2X-121 in patients with mBC
Timespan
Overall survival (OS) after administration of 2X-121 in patients with mBC
Timespan
Performance status (ECOG)
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
Adverse Events as assessed by CTCAE v4. to evaluate safety profile after administration of 2X-121 in patients with mBC
Full Information
NCT ID
NCT03562832
First Posted
April 26, 2018
Last Updated
July 19, 2023
Sponsor
Allarity Therapeutics
Collaborators
Smerud Medical Research International AS, Danish Breast Cancer Cooperative Group
1. Study Identification
Unique Protocol Identification Number
NCT03562832
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 20, 2018 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allarity Therapeutics
Collaborators
Smerud Medical Research International AS, Danish Breast Cancer Cooperative Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
PARP inhibitor, Drug Response Prediction (DRP), Tankyrase 1/2 inhibitor, mRNA biomarker
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PARP inhibitor 2X-121
Arm Type
Experimental
Arm Description
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
Intervention Type
Drug
Intervention Name(s)
PARP inhibitor 2X-121
Intervention Description
600 mg PARP inhibitor 2X-121 as single daily oral agent in mBC patients
Primary Outcome Measure Information:
Title
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
Description
Overall tumor response according to RECIST
Time Frame
one year
Secondary Outcome Measure Information:
Title
Progression free survival (PFS) after administration of 2X-121 in patients with mBC
Description
Timespan
Time Frame
one year
Title
Duration of objective response after administration of 2X-121 in patients with mBC
Description
Timespan
Time Frame
one year
Title
Overall survival (OS) after administration of 2X-121 in patients with mBC
Description
Timespan
Time Frame
one year
Title
Performance status (ECOG)
Description
To evaluate change in patient performance status by ECOG (Eastern Cooperative Oncology Group) Performance Status by a 6-step classification system
Time Frame
one year
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Adverse Events as assessed by CTCAE v4. to evaluate safety profile after administration of 2X-121 in patients with mBC
Time Frame
one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Facility Information:
Facility Name
Herlev and Gentofte Hospital, Herlev Ringvej 75, DK-2730 Herlev
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Vejle Sygehus
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.oncologyventure.com
Description
Official Homepage of Sponsor
Learn more about this trial
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
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