9-ING-41 in Patients With Advanced Cancers

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03678883
• Other study ID #: 1801
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 4, 2019
• Est. completion date: November 2025

Study information

• Verified date: March 2024
• Source: Actuate Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

• Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.

• Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.

• Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 350
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Part 3 ARMB 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 metastatic pancreatic cancer AND is previously untreated with systemic agents in the recurrence/metastatic setting.

4. Must have at least 1 measurable lesion per RECIST v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)

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

e. Adequate bone marrow function: absolute neutrophil count (ANC) = 500/mL; hemoglobin = 8.5 g/dL, platelets = 75,000/mL f. Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase = 3 (= 10 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 Adequate renal function: creatinine clearance = 30 mL/min (Cockcroft and Gault)

6. Has Eastern Co-operative Oncology Group (ECOG) PS 0 or 1

7. Has received the final dose of any of the following treatments/ procedures with the specified minimum intervals before first dose of study drug:

• Focal radiation therapy - 7 days

• Surgery with general anesthesia - 7 days

• Surgery with local anesthesia - 3 days

8. May have received treatment with fluorouracil or gemcitabine as a radiation sensitizer in the adjuvant setting if the treatment was received at least 6 months before study enrollment

9. May have received neoadjuvant chemotherapy with FOLFIRINOX if last dose given at least 6 months before study enrollment

10. May have received prior cytotoxic doses of systemic chemotherapy in the adjuvant setting if last dose given at least 6 months before study enrollment

11. 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

12. 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

13. Must not be receiving any other investigational medicinal product

Patient who meets ANY of the following criteria is not eligible for this Part 3 study Arm B:

Exclusion Criteria:

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 endocrine or acinar pancreatic carcinoma

4. Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and/or infertility. Recovery is defined as = Grade 2 severity per CTCAE, v5.0

5. 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 study therapy, or uncontrolled cardiac arrhythmia

6. Has had a myocardial infarction within 12 weeks of the first dose of study therapy or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator

7. Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Patients with stable 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

8. 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)

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

10. 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.

11. Has a current active malignancy other than pancreatic cancer

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

Related Conditions & MeSH terms

• Bone Cancer
• Bone Metastases
• Bone Neoplasm
• Bone Neoplasms
• Breast Neoplasms
• Cancer
• Colorectal Neoplasms
• Glioma
• Kidney Neoplasms
• Leukemia, T-Cell
• Lung Neoplasms
• Lymphoma
• Malignancies
• Malignancies Multiple
• Malignant Glioma
• Neoplasm Metastasis
• Neoplasm of Bone
• Neoplasm of Lung
• Neoplasm, Breast
• Neoplasms
• Neoplasms Pancreatic
• Neoplasms,Colorectal
• Pancreas Cancer
• Pancreatic Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Neoplasms
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Refractory Cancer
• Refractory Neoplasm
• Refractory Non-Hodgkin Lymphoma
• Renal Cancer
• Resistant Cancer
• Sarcoma

Intervention

Drug:
• 9-ING-41
Starting dose of-9-ING-41 will be administered on Day 1 and 4 each week of a 21-day cycle. 9-ING-41 will be administered intravenously over 60 minutes.
• Gemcitabine - 21 day cycle
Gemcitabine 1250 mg/m2 as a 30-minute intravenous infusion on Days 1 and 8 of a 21-day cycle
• Doxorubicin.
Doxorubicin 75 mg/m2, intravenous bolus on Day 1 of a 21-day cycle up to a maximum lifetime dose of 550 mg/m2.
• Lomustine
Lomustine 30 mg/m² orally as a single dose, weekly for twelve weeks.
• Carboplatin.
Carboplatin AUC 6 IV over 1 hour on Day 1 of a 21-day cycle.
• Nab paclitaxel.
Nab-paclitaxel 125 mg/m2 intravenously on Days 1, 8 and 15 of a 28-day cycle
• Paclitaxel.
Paclitaxel 175 mg/m2 intravenously over 3 hours on Day 1 of a 21-day cycle.
• Gemcitabine - 28 day cycle
Gemcitabine 1000 mg/m2 intravenously over 30-minutes on Days 1, 8 and 15 of a 28-day cycle
• Irinotecan
Irinotecan 350 mg/m2 intravenously over 90-minutes on Day 1 of a 21-day cycle

Locations

Country	Name	City	State
Belgium	Imelda VZW	Bonheiden
Belgium	UZA- Antwerpen	Edegem	Antwerp
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre	Greenfield Park	Quebec
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	Jewish General Hospital	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Centre Hospitalier Universitaire de Sherbrooke	Sherbrooke	Quebec
France	Center Hospitalier Regional Universitaire de Besancon - Site Jean Minjoz	Besançon	Bourgogne-Franche-Comte
France	Institut Bergonie	Bordeaux	Nouvelle Aquitaine
France	CHRU Brest Hopital Morvan	Brest	Bretagne
France	Hopital Claude Huriez	Lille	Hauts De France
France	Hopital de la Timone	Marseille
France	Insitut de Cancerologie de l'Ouest	Saint-Herblain	Pays-de-la-Loire
France	Institute de Cancerologie de Lorraine	Vandœuvre-lès-Nancy	Meurthe-et-Moselle
Netherlands	Netherlands Cancer Institute	Amsterdam
Portugal	Fundacao Champalimaud	Lisbon
Portugal	Hospital Da Luz	Lisbon
Portugal	Centro Hospitalar Universitario Sao Joao	Porto
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Clinico U San Carlos (HSC)	Madrid
Spain	START Madrid-HM CIOCC Hospital Universitario	Madrid
Spain	INCLIVA University of Valencia	Valencia
United States	University of Michigan	Ann Arbor	Michigan
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Texas Oncology- Charles A. Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Des Moines Oncology Research Association	Des Moines	Iowa
United States	Duke University Medical Center	Durham	North Carolina
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	West Cancer Center	Germantown	Tennessee
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	Kansas University Cancer Center	Kansas City	Kansas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	UW Carbone Cancer Center	Madison	Wisconsin
United States	Baptist Clinical Research Institute	Memphis	Tennessee
United States	Miami Cancer Institute	Miami	Florida
United States	MetroMetro-Minnesota Community Oncology Research Consortium (MMCORC)	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Sarah Cannon Research Institute- Tennessee Oncology-Nashville	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University- Irving Medical Center	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	University of California Irvine Health	Orange	California
United States	Capital Health Medical Center/ Hopewell	Pennington	New Jersey
United States	Mayo Clinic	Phoenix	Arizona
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Florida Cancer Specialists - North	Saint Petersburg	Florida
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Sanford Research	Sioux Falls	South Dakota
United States	Stony Brook University Hospital	Stony Brook	New York
United States	Arizona Oncology Associates	Tucson	Arizona
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	MD Anderson Cancer Center at Cooper	Voorhees	New Jersey
United States	Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Actuate Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Netherlands,  Portugal,  Spain, 

References & Publications (13)

Anraku T, Kuroki H, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar A, Giles FJ, Ugolkov A, Tomita Y. Clinically relevant GSK-3beta inhibitor 9-ING-41 is active as a single agent and in combination with other antitumor therapies in human renal cancer. Int J — View Citation

Ding L, Madamsetty VS, Kiers S, Alekhina O, Ugolkov A, Dube J, Zhang Y, Zhang JS, Wang E, Dutta SK, Schmitt DM, Giles FJ, Kozikowski AP, Mazar AP, Mukhopadhyay D, Billadeau DD. Glycogen Synthase Kinase-3 Inhibition Sensitizes Pancreatic Cancer Cells to Ch — View Citation

Jeffers A, Qin W, Owens S, Koenig KB, Komatsu S, Giles FJ, Schmitt DM, Idell S, Tucker TA. Glycogen Synthase Kinase-3beta Inhibition with 9-ING-41 Attenuates the Progression of Pulmonary Fibrosis. Sci Rep. 2019 Dec 12;9(1):18925. doi: 10.1038/s41598-019-5 — View Citation

Karmali R, Chukkapalli V, Gordon LI, Borgia JA, Ugolkov A, Mazar AP, Giles FJ. GSK-3beta inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents. Oncotarget. — View Citation

Kuroki H, Anraku T, Kazama A, Bilim V, Tasaki M, Schmitt D, Mazar AP, Giles FJ, Ugolkov A, Tomita Y. 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977. — View Citation

Pal K, Cao Y, Gaisina IN, Bhattacharya S, Dutta SK, Wang E, Gunosewoyo H, Kozikowski AP, Billadeau DD, Mukhopadhyay D. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer. Mol Cancer Ther. 2014 Feb;13(2):285-96. doi — View Citation

Sahin I, Eturi A, De Souza A, Pamarthy S, Tavora F, Giles FJ, Carneiro BA. Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses. Cancer Biol Ther. 2019;20(8):1047-1056. doi: 10.1080/15384047.20 — View Citation

Ugolkov A, Gaisina I, Zhang JS, Billadeau DD, White K, Kozikowski A, Jain S, Cristofanilli M, Giles F, O'Halloran T, Cryns VL, Mazar AP. GSK-3 inhibition overcomes chemoresistance in human breast cancer. Cancer Lett. 2016 Oct 1;380(2):384-392. doi: 10.101 — View Citation

Ugolkov A, Qiang W, Bondarenko G, Procissi D, Gaisina I, James CD, Chandler J, Kozikowski A, Gunosewoyo H, O'Halloran T, Raizer J, Mazar AP. Combination Treatment with the GSK-3 Inhibitor 9-ING-41 and CCNU Cures Orthotopic Chemoresistant Glioblastoma in P — View Citation

Ugolkov AV, Bondarenko GI, Dubrovskyi O, Berbegall AP, Navarro S, Noguera R, O'Halloran TV, Hendrix MJ, Giles FJ, Mazar AP. 9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma. Anticancer Drugs. 2018 Sep;29(8):717-7 — View Citation

Ugolkov AV, Matsangou M, Taxter TJ, O'Halloran TV, Cryns VL, Giles FJ, Mazar AP. Aberrant expression of glycogen synthase kinase-3beta in human breast and head and neck cancer. Oncol Lett. 2018 Nov;16(5):6437-6444. doi: 10.3892/ol.2018.9483. Epub 2018 Sep — View Citation

Walz A, Ugolkov A, Chandra S, Kozikowski A, Carneiro BA, O'Halloran TV, Giles FJ, Billadeau DD, Mazar AP. Molecular Pathways: Revisiting Glycogen Synthase Kinase-3beta as a Target for the Treatment of Cancer. Clin Cancer Res. 2017 Apr 15;23(8):1891-1897. — View Citation

Wu X, Stenson M, Abeykoon J, Nowakowski K, Zhang L, Lawson J, Wellik L, Li Y, Krull J, Wenzl K, Novak AJ, Ansell SM, Bishop GA, Billadeau DD, Peng KW, Giles F, Schmitt DM, Witzig TE. Targeting glycogen synthase kinase 3 for therapeutic benefit in lymphoma — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1/2: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	The standard assessments used to assign a score to any affected organ system as per the NCI CTCAE 4.03 will be conduced at each protocol-specified timepoint.	3 months to 3 years
Primary	Part 3 Arm B	To determine the 1-year survival rate of patients treated on the 9-ING-41 schedule chosen from the run-in stage of the study compared to the control arm	3 months to 3 years