Safety and Efficacy Study of KX2-391 for Treatment of Bone-Metastatic, Castration-Resistant Prostate Cancer

NCT01074138 | Completed Phase 2

• 1 other identifier: KXO1-002-09
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 5

Brief Summary

The standard of care for patients with bone-metastatic, castrate-resistant prostate cancer is chemotherapy. If a patient elects not to choose chemotherapy, 70% will progress within 6 months. KX2-391 given orally twice a day for 6 months will be evaluated for its ability to delay/prevent disease progression in patients who have not had prior chemotherapy.

Conditions

Bone-Metastatic, Castration-Resistant Prostate Cancer

Keywords

CPRC

Outcome Measures

Primary Outcomes (1)

• The proportion of patients who do not have clinical or radiographic progression

  At screening/baseline, target lesions will be identified and measured by CT scan and bone lesions will be enumerated by bone scintigraphy. At 12 and 24 weeks after treatment with KX2-391, patients will be assessed by CT and bone scan to assess whether radiographic progression has occurred. At monthly visits and throughout the study, clinical progression will be evaluated.

  24 weeks

Secondary Outcomes (2)

• Determine the proportion of patients who do not have PSA progression

  24 weeks

• Determine the pharmacokinetics of KX2-391

  24 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Subjects will be enrolled into a 28-day dose-escalation study. If no DLT's are observed during the first 28 days, subjects are eligible to continue treatment in the Extension Phase and can remain on treatment until toxicity occurs or until disease progression.

Drug: KX2-391

Interventions

KX2-391 DRUG

KX2-391 will be administered as a 40 mg oral dosing solution, twice daily, for 6 28-day cycles.

Also known as: KXO1

Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must provide signed informed consent prior to performing any study-related procedures;
• The patient must have histologically or cytologically confirmed prostate adenocarcinoma;
• The patient must have presence of at least one documented osseous metastasis on bone scan;
• The patient must have a castrate testosterone level \<50ng/dl within 4 weeks prior to initiation of KX2-391 treatment. If chemically castrate, the patient must also agree to stay on luteinizing hormone releasing hormone (LHRH) agonist medication for the duration of the study;
• The patient must have documented disease progression as evidenced by one or more of the following 3 criteria:
• Rising PSA, defined as three rising PSA values ≥ 2 weeks apart with the 3rd value 2ng/ml or greater (historical values may be used). Rising PSA must be seen in the 3rd value relative to the 2nd value AND in the 2nd value relative to the 1st value (i.e. two consecutive rises over time muse be noted). Given potential for fluctuations in PSA values, one drop in rising PSA values over time may be seen when determining eligibility. Pre-therapy PSA doubling time may also be calculated (if there are 3 or more values 4 or more weeks apart.
• Evidence of nodal or visceral progression. Progression must be evident within 3 months prior to study entry.
• Radiographic documentation of disease is required by CT (or MRI, when CT is not available)(using RECIST 1.1 criteria) within 4 weeks of study entry.The patient must have at least 1 unidimensionally measurable lesion ≥ 20mm by conventional techniques (i.e., conventional CT or chest x-ray) OR ≥ 10mm by spiral CT scan.Only lymph nodes ≥ 20mm in diameter may be counted.CT is preferred over MRI. The radiographic measurement technique used at Baseline must be serially used throughout the duration of the study.
• Evidence of progression of bone metastases on bone scan. Appearance of ≥ 2 new lesions since the prior scan (prior scan obtained within 3 months of study entry).Documentation of bone metastases by bone scintigraphy (using PCWG2 criteria) within 4 weeks of study entry.
• The patient must have no known brain metastases (confirmation by CT and/or MRI is not required);
• The patient be a ≥ 18 year old male at the time of enrollment;
• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2;
• The patient must have an estimated life expectancy of ≥ 6 months;
• The patient must have adequate hematopoietic function as demonstrated by 1) hemoglobin of ≥ 9.0g/dL, 2) platelet count ≥ 100,000ul, 3) WBC count ≥ x109/L, and 4) ANC ≥ 1.5 x109/L;
• The patient must have adequate hepatobiliary function as demonstrated by 1) a bilirubin level ≤ 1.5 times the upper limit of normal (ULN), unless the patient has Gilbert's syndrome in which case he/she must have a bilirubin level ≤ 2.5 times the upper limit of normal and 2) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times the ULN;

You may not qualify if:

• The patient has had other prior malignancy (with the exception of basal cell or squamous cell carcinoma of the skin and superficial transitional cell carcinoma of the bladder) within 3 years of study entry;
• The patient has peripheral neuropathy ≥ grade 2 as defined using Common Terminology Criteria for Adverse Events (CTCAE);
• The patient has uncontrolled diabetes mellitus in the opinion of the Investigator;
• The patient has experienced hemoptysis or significant bleeding episode within 6 months prior to enrollment;
• The patient has had upper or lower gastrointestinal (GI) bleeding within 6 months prior to enrollment;
• The patient has had a GI perforation within 12 months prior to enrollment;
• The patient has had major surgery of the GI tract or a history of inflammatory bowel disease, malabsorption syndrome or other medical condition that would interfere with oral drug absorption;
• The patient has a serious or non-healing wound or ulcer;
• The patient has a known history of pathological bone fracture;
• The patient has a known history of hepatitis B, C, or human immunodeficiency virus (HIV) infection;
• The patient received moderate or strong CYP450 3A4 modulators (inducers or inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) prior to initiation of KX2-391 dosing and during the study;
• The patient received prior treatment with estramustine or suramin;
• The patient received treatment with flutamide, bicalutamide, nilutamide, or ketoconazole within 4 weeks of study entry;
• The patient received prior chemotherapy for prostate cancer;
• The patient received 5α-reductase inhibitors (e.g., finasteride, dutasteride) within 4 weeks of study entry;

Sponsors & Collaborators

• Athenex, Inc.: lead

Study Sites (5)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Wayne State University-Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. doi: 10.1200/JCO.2007.12.4487.

  PMID: 18309951 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

MeSH Terms

Interventions

tirbanibulin

Study Officials

• Michael Carducci, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Min-Fun Rudolf Kwan, MD

  Kinex Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2010
• First Posted: February 24, 2010
• Study Start: February 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: October 1, 2012
• Last Updated: February 2, 2023

Record last verified: 2023-02

Locations

US (5)