9-ING-41 in Patients With Advanced Cancers

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

Summary

GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Actuate Therapeutics Inc.
• Collaborator: Developmental Therapeutics Consortium
• Treatments: Albumin-Bound Paclitaxel; Carboplatin; Doxorubicin; Gemcitabine; Irinotecan; Liposomal doxorubicin; Lomustine; Paclitaxel

Criteria

Inclusion Criteria:

• Patient -

1. Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.

2. Is aged ≥ 18 years

3. Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following:

1. Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition

2. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit

3. Malignancy has relapsed after standard therapy

4. Malignancy for which there is no standard therapy that improves survival by at least 3 months

4. Has evaluable tumor(s) by standard radiological and/or laboratory assessments as applicable to their malignancy - in Part 3, patients with solid tumors must have least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI). In the case of patients with glioblastoma multiforme (GBM) or other central nervous system (CNS) tumors, the tumor must be measurable, defined as a clearly enhancing tumor with at two perpendicular diameters at entry equal or superior to 1cm.

5. Has laboratory function within specified parameters (may be repeated):

1. Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 500/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/mL

2. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 3 (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells) x ULN; bilirubin ≤ 1.5 x ULN

3. Adequate renal function: creatinine clearance ≥ 60 mL/min (Cockcroft and Gault)

4. Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3

5. Serum amylase and lipase ≤ 1.5 x ULN

6. Has adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS 0-2

7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug (unless in the opinion of the investigator and the study medical coordinator the treatments/ procedures will not compromise patient safety or interfere with study conduct and with IDMC agreement):

• Chemotherapy, immunotherapy, or systemic radiation therapy - 14 days or ≥ 5 half-lives (whichever is shorter)

• Focal radiation therapy - 7 days

• Systemic and topical corticosteroids - 7 days

• Surgery with general anesthesia - 7 days

• Surgery with local anesthesia - 3 days

8. May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study

9. Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first study therapy. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 90 days after discontinuation of study treatment

10. Male patients with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 90 days after discontinuation of study treatment and use appropriate barrier contraception or true abstinence

11. Must not be receiving any other investigational medicinal product

Exclusion Criteria:

• Patient -

1. Is pregnant or lactating

2. Is known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation

3. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as ≤ Grade 2 CTCAE Version 4.03

4. Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening

5. Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator

6. Has known symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable asymptomatic brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug

7. Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges), the surgery is considered major)

8. Has any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation

9. Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial

10. Has a current active malignancy other than the target cancer

11. Is considered to be a member of a vulnerable population (for example, prisoners)