Actuate 1801: Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined with Chemotherapy, in Patients with Refractory Hematologic Malignancies or Solid Tumors

Study Name
Actuate 1801: Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined with Chemotherapy, in Patients with Refractory Hematologic Malignancies or Solid Tumors
ClinicalTrials.gov Identifier (if applicable)
NCT03678883
Clinical Trial Category (check all that apply)
  • Beyond First Line Therapy
  • Chemotherapy
  • Targeted Therapy
  • Other Novel Therapy
Study Center
Institution Name
Rhode Island Hospital
Institution Address
rovidence, Rhode Island, United States, 02903
City
Providence
State
Rhode Island
Zip Code
02903
Country
United States
Phone
(401) 444-3234
Website
https://www.lifespan.org/centers-services/cancer-research-and-clinical-trials
Study Contacts
Principal Investigator
Benedito Carneiro, MD
P.I. Phone
(401) 444-3234
P.I. Email
Benedito.Carneiro@Lifespan.org
Study Coordinator
Jennifer Renaud
Study Coordinator Phone
(401) 444-3234
Study Coordinator Email
JRenaud@Lifespan.org
OVERVIEW – in layman’s terms (150 words max)
A clinical trial of a new drug known as 9-ING-41, that will take place in
patients with tumors or cancers that affect the blood and lymph system.
9-ING-41 be assessed as a standalone drug as well as being assessed
when taken with chemotherapy drugs.
Enrollment
Ongoing
Study Start Date
12/12/2018
Estimated Completion Date
12/31/2020
Purpose of the Study – in Layman’s Terms (use the “+” to add more list items)
  • Test the safety of 9-ING-41 on its own and see what effects (good and bad) it has on you and your cancer
  • Test the safety of 9-ING-41 in combination with chemotherapy and see what effects (good and bad) they have on you and your cancer
  • Find the highest dose of 9-ING-41, alone and with other chemotherapy drugs that can be given without causing bad side effects
  • Examine how much 9-ING-41 is in the blood at certain times after it is given and how quickly the body gets rid of it
  • Observe whether there is any effect of 9-ING-41 alone or in combination with chemotherapy on the size and activity of cancer in your body
Inclusion Criteria – Patients Must:
  • Be 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.
  • Be aged ≥ 18 years
  • Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following: Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition; Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit; Malignancy has relapsed after standard therapy; Malignancy for which there is no standard therapy that improves survival by at least 3 months
  • Have 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.
  • Have laboratory function within specified parameters (accounting for bone marrow function, liver/kidney function, blood coagulation, pancreatic enzyme levels)
  • Have adequate performance status (PS): Eastern Co-operative Oncology Group (ECOG) PS 0-1
  • Have 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 – 21 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
  • May continue endocrine therapies (e.g. for breast or prostate cancer) and/or anti-human epidermal growth factor (Her2) therapies while on this study
  • 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
  • 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
  • Must not be receiving any other investigational medicinal product
  • For study Parts 2 and 3, must have received prior therapy for the same malignancy including the same potential partner agent(s) as that/those being considered for administration on study in combination with 9-ING-41
Exclusion Criteria – Patients Must NOT:
  • Be pregnant or lactating
  • Be known to be hypersensitive to any of the components of 9-ING-41 or to the excipients used in its formulation
  • Have not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as ≤ CTCAE) Version 4.03
  • Have 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
  • Have 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
  • Have 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
  • Have 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)
  • Have any medical and/or social condition which, in the opinion of the investigator or study medical coordinator would preclude study participation
  • Have received an investigational anti-cancer drug in the 21-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
  • Have had a previous (within 2 years) or has a current malignancy other than the target cancer with the exception of curatively treated local tumors including carcinoma in situ of the breast or cervix, basal or squamous cell carcinoma of the skin, or prostate cancer with Gleason Grade < 6 and prostate-specific antigen within normal range
  • Be considered to be a member of a vulnerable population (for example, prisoners)
  • For Study Parts 2 and 3, must not have developed persistent (>28 days) clinically significant Grade 3/4 toxicities attributable to same prior chemotherapy agent as that being considered for administration on this study in combination with 9-ING-41
  • During Parts 1 and 2 of the study, patients taking strong inhibitors of CYP2C19, CYP3A4, and CYP1A2 or strong inducers of CYP3A4 should not be entered into the study protocol; this will be reviewed by the IDMC prior to Part 3 of the study opening to recruitment
REQUIRED TESTS PRIOR TO BEGINNING STUDY TREATMENT – in layman’s terms
  • You will be asked questions regarding your medical history (past and current medical history, including smoking and alcohol habits, and the medical history of your cancer)
  • Your weight and height will be measured
  • Women will be asked about use of contraceptives and child bearing potential. We will check that you are not pregnant
  • You will be physically examined by the study doctor and we will assess your performance status
  • You will be asked for other medications you are taking (e.g. concomitant therapies), including vitamins and supplements
  • Your heart rate and blood pressure will be measured
  • A fresh biopsy of your cancer will be taken if that is possible and no biopsy was performed prior to screening
  • You will have a 12-lead electrocardiogram (ECG)
  • You will have some blood tests including a complete blood count with differential and platelets, a comprehensive metabolic panel, coagulation study (INR) and pancreatic enzymes (amylase and lipase). If your tumor can be assessed by measuring any tumor markers in the blood, these will be taken too
  • If not done within the prior 6 weeks, a positron emission tomography (PET)/CT scan, MRI, and/or CT scan will be performed for radiological evaluation of disease. Bone imaging will be performed as appropriate according to the judgment of your doctor
  • If your cancer is on the skin, it will be measured. No photographs are required
POTENTIAL SIDE-EFFECTS – in layman’s terms
  • This is the first time that 9-ING-41 has been given to humans
  • Possible side effects could include a worsening of any adverse effects of the chemotherapy agents given in combination with 9-ING-41
  • Possible side effects could include skin reactions
  • Possible side effects could include damage at the site of 9-ING-41 intravenous administration (local vascular tissue injury), including the potential for development of a blood clot at the injection site
  • Possible side effects could include decreased production of sperm in men
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