Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT05571969|
Recruitment Status : Recruiting
First Posted : October 7, 2022
Last Update Posted : February 2, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: 2X-121 and dovitinib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This is a Phase Ib, two-part, multi-center study. In Part 1, the study will evaluate the safety and tolerability, antitumor activity, pharmacokinetics, and determine the maximum tolerated dose (MTD) of 2X-121 monotherapy (at BID regimen) in patients with advanced solid tumors. In Part 2, the study will evaluate the safety and tolerability, antitumor activity, and pharmacokinetics of 2X-121 (MTD) and dovitinib as combination therapy, and determine the MTD of dovitinib when given in combination with the MTD of 2X-121 determined in Part 1.|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib, Open Label, Multicenter Study to Determine the Maximum Tolerated Dose (MTD) of PARPi 2X-121 Monotherapy and the MTD of Dovitinib in Combination With 2X-121 in Patients With Advanced Solid Tumors|
|Estimated Study Start Date :||February 20, 2023|
|Estimated Primary Completion Date :||October 2024|
|Estimated Study Completion Date :||December 2024|
Experimental: 2X-121 Monotherapy and Dovitinib in Combination with 2X-121 in Patients with Advanced Solid Tumors
Determine the maximum tolerated dose (MTD) of 2X-121 monotherapy given twice daily (BID) and determine the MTD of dovitinib given in combination with 2X-121 (MTD) in patients with advanced solid tumors.
Drug: 2X-121 and dovitinib
The dose levels to be evaluated in Part 1 are:
Cohort 1 600 mg (morning dose: 200 mg + evening dose: 400 mg); Cohort 2 800 mg (morning dose: 400 mg + evening dose: 400 mg); Cohort 3 1000 mg (morning dose: 400 mg + evening dose: 600 mg);
The dose levels to be evaluated in Part 2 are:
Cohort 1 2X-121 (MTD) + 300 mg dovitinib; Cohort 2 2X-121 (MTD) + 400 mg dovitinib; Cohort 3 2X-121 (MTD) + 500 mg dovitinib;
- Determination of the MTD of 2X-121 monotherapy. [ Time Frame: Evaluated after up to approximately 2 years ]To determine the maximum tolerated dose (MTD) of 2X-121 monotherapy given twice daily (BID) in patients with advanced solid tumors.
- Determination of the MTD of dovitinib given in combination with 2X-121 (MTD). [ Time Frame: Evaluated after up to approximately 2 years ]To determine the MTD of dovitinib given in combination with 2X-121 (MTD) in patients with advanced solid tumors.
- To evaluate the objective response rate (ORR) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2). [ Time Frame: Evaluated after up to approximately 2 years ]ORR is defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1.
- To evaluate the duration of overall response (DOR) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2). [ Time Frame: Evaluated after up to approximately 2 years ]DOR is defined as the time in months from the first documented CR or PR per RECIST v. 1.1 to disease recurrence or disease progression (PD) whichever occurs first.
- To evaluate progression free survival (PFS) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2). [ Time Frame: Evaluated after up to approximately 2 years ]PFS is defined as the time from study treatment initiation to either first observation of progressive disease or occurrence of death.
- To evaluate overall survival (OS) of 2X-121 monotherapy (Part 1) and in combination with dovitinib (Part 2). [ Time Frame: Evaluated after up to approximately 2 years ]OS is defined as the time from study treatment initiation to death from any cause or last day known to be alive.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Age 18 years or older.
- Histologically or cytological documented solid tumor.
- Available tumor biopsy (most recent) for DRP® analysis.
- Measurable disease by CT scan or MRI if possible.
- Performance status of ECOG ≤ 1.
- Recovered to Grade <1 or baseline 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 anti-epileptic drugs are allowed.
Adequate conditions as evidenced by the following clinical laboratory values:
- Absolute neutrophils count (ANC) ≥ 1500/mm3 (1.5 x 10³/mL)
- Hemoglobin > 10.0 g/dL
- Platelets ≥ 100,000/mm3 (≥ 100 x 10⁹/L)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN or ≤5x ULN in presence of liver metastases
- Serum bilirubin ≤ 1.5 ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Creatinine ≤ 1.5 ULN
- Blood urea nitrogen (BUN) ≤2X ULN.
- Life expectancy equal or longer than 3 months.
- The subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided and has had the opportunity to discuss the study with the investigator or designee.
- The subject is able to communicate satisfactorily with the investigator and to participate in, and comply with, the requirements of the study.
- The subject is able to understand the nature of the study and any potential hazards associated with participating in it.
- Negative pregnancy test for female subjects of childbearing potential. Women of childbearing potential (WOCBP) and Women of non-childbearing potential are eligible to participate. Both women of childbearing potential and women of non-childbearing potential should use an approved method of birth control and agree to continue to use this method for the duration of the study (and for 90 days after taking the last dose of study drug).
Acceptable methods of contraception include abstinence, female subject/partner's use of hormonal contraceptive (oral, implanted, or injected) in conjunction with a barrier method (WOCBP only) (e.g., diaphragm, cervical cap, male condom, and female condom and spermicidal foam, sponges, and film), female subject/partner's use of an intrauterine device (IUD), or if the female subject/partner is surgically sterile for at least three months before screening or 2 years post-menopausal at time of screening. All male subjects/partners must agree to consistently and correctly use a condom for the duration of the study and for 90 days after taking the study drug. In addition, subjects may not donate sperm for the duration of the study and for 90 days after taking study drug.
- 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.
- Any active infection requiring parenteral or oral antibiotic treatment.
History of coagulation or bleeding disorder or subject currently on therapeutic anticoagulant medication.
Note: Prophylactic doses of heparin or low molecular weight heparin are allowed.
- Known HIV positivity.
- Known active hepatitis B or C.
Clinically significant (i.e. active) cardiovascular disease:
- Stroke within ≤ 6 months prior to day 1
- Transient ischemic attack (TIA) within ≤ 6 months prior to day 1
- Myocardial infarction within ≤ 6 months prior to day 1
- Unstable angina
- New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
- Serious cardiac arrhythmia requiring medication.
- Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation for 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 and dovitinib.
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05571969
|Contact: Marie Foegh, MD, DrSc||+1 (201) 314 email@example.com|
|United States, North Carolina|
|Huntersville, North Carolina, United States, 28078|
|Contact: Hannah White 704-947-6597|
|Principal Investigator: John D Powderly, MD|
|United States, Ohio|
|University Hospitals Cleveland Medical Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Kim Thomas 216-844-3997|
|Principal Investigator: Afshin Dowlati, MD|
|Responsible Party:||Allarity Therapeutics|
|Other Study ID Numbers:||
|First Posted:||October 7, 2022 Key Record Dates|
|Last Update Posted:||February 2, 2023|
|Last Verified:||February 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|