AzTrials
AzTrials

Bone-Metastatic, Castration-Resistant Prostate CancerPhase 2NCT01074138

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

A Phase 2 study testing KX2-391 in people with Bone-Metastatic, Castration-Resistant Prostate Cancer, run by Athenex, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years, men only
What is being tested?
KX2-391
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
5 sitesUnited States
Study dates
Feb 2010to Oct 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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;
  • The patient must have adequate renal function as demonstrated by a creatinine level ≤ 1.5 times the ULN and a creatinine clearance (measured or calculated) ≥ 35 mL/min;
  • Patients with partners of child-bearing potential must be willing to abstain from sexual activity or practice physical barrier contraception during study participation and for at least 3 months after completion of KX2-391 treatment;
  • The patient must be able to self-administer KX2-391 and agree to adhere to the study visit schedule; study treatment schedule and other protocol requirements.

Who cannot join

  • 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 a history of major cardiovascular or neurologic disease within the 6 months prior to enrollment, including, but not limited to, uncontrolled hypertension (at the discretion of the Investigator)< NYHA Class III or IV congestive heart failure, myocardial infarction, confirmed significant cardiac conduction abnormalities (including QTc > 0.45 sec) or arrhythmias, cerebrovascular accident(s), transient ischemic attack(s), clinically significant peripheral artery disease (i.e., claudication on walking less than one block), or other major arterial thrombotic events (e.g., pulmonary embolism) (Note: Patients with deep venous thrombosis are eligible for inclusion if they have been on a stable dose of anticoagulation therapy for at least 4 weeks prior to 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;
Show all 34Show fewer
  • 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;
  • The patient received other hormonal therapy [e.g., aminoglutethimide, megestrol, diethylstilbestrol (DES)] within 6 weeks of study entry;
  • The patient is on other concurrent endocrine therapy, the exception of 1) steroids for adrenal insufficiency or autoimmune disease, if on a stable dose for > 3 months, 2) intermittent dexamethasone as an antiemetic (to be avoided, if at all possible); and 3) hormones for non-disease-related illnesses (e.g. insulin for diabetes);
  • The patient received strontium chloride (Sr89) or samarium (Sm153) lexidronam pentasodium therapy within 12 weeks of study entry;
  • The patient received extensive radiation therapy (including sternum, pelvis, scapulae, vertebrae or skull) within 4 weeks of study entry;
  • The patient received extensive radiation therapy > 4 weeks before study entry and has not recovered from side effects of therapy;
  • The patient received palliative low dose radiation therapy limited to the limbs within 2 weeks of initiating KX2-391;
  • The patient is on bisphosphonates and the dose has changed in the 4 weeks prior to study entry (initiation of bisphosphonates during the study is not permitted);
  • The patient is receiving full-dose anticoagulation therapy and dose has been modified in the 4 weeks prior to study entry (patients on low molecular weight heparin or aspirin are eligible for study enrollment);
  • PT or INR is > 1.5 times the upper limit of normal and the patient is not on any anti-coagulation therapy or anti-platelet agents;
  • The patient is expected to initiate chemotherapy or palliative radiotherapy while on the study;
  • The patient is either currently receiving or is expected to receive treatment with filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) during the study period (these medications and therapies may only be initiated when clinically indicated during the study);
  • The patient has had major surgery within 4 weeks of study entry;
  • The patient has had major surgery within > 4 weeks prior to study entry and has not fully recovered from the surgery;
  • The patient received other investigational agents/therapies within 28 days of study entry;
  • The patient has persistent ≥ grade 2 treatment-related toxicity from prior anti-cancer therapy, including other investigational agents;
  • The patient has any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study, including, but not limited to, end organ failure, coagulation disorder, hemolytic condition (e.g. sickle cell disease) or active infection;
  • The patient has any other condition(s) which could significantly interfere with protocol compliance, including, but not limited to, dementia, psychosis, cognitive impairment, or other major psychiatric disorder;
  • The patient has previously participated in the Phase I clinical trial of KX2-391.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21205

  • University of Chicago

    Chicago, Illinois, 60637

  • Wayne State University-Karmanos Cancer Center

    Detroit, Michigan, 48201

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • University of Washington

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II, Open-Label, Single-Arm Study Evaluating the Safety, Efficacy and Pharmacokinetics of KX2-391 in Patients With Bone-Metastatic, Castration-Resistant Prostate Cancer Who Have Not Had Prior Chemotherapy

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.

Read the detailed description

This is a multi-center, single-arm, open-label, prospective phase II clinical trial evaluating the efficacy, safety and pharmacokinetics of orally administered KX2-391 in adult male patients with progressive bone-metastatic CRPC. Patients must have 1) documented bone-metastatic prostate cancer, 2) castrate levels of testosterone, 3) not received prior chemotherapy, and 4) documented disease progression based on rising PSA, progressive measurable visceral disease and/or progressive bone lesions (one criteria is sufficient) as per the Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines (Scher et al 2008).

Being tested
KX2-391
Keywords
CPRC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KX2-391Drug

    Also called KXO1

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

Study groups in NCT01074138
Study groupRoleWhat they receive
TreatmentExperimentalSubjects 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.
Receives: Drug: KX2-391

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 24 weeks

Secondary outcomes (2)

  1. Determine the proportion of patients who do not have PSA progression

    PSA will be measure at baseline and at the start of each of 6, 28 day cycles

    Measured: 24 weeks

  2. Determine the pharmacokinetics of KX2-391

    Pharmacokinetic parameters will be determined in patients receiving 40 mg KX2-391, twice daily.

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionJun 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01074138
Sponsor's protocol ID
KXO1-002-09
Status last verified
Feb 2023
First submitted
22 Feb 2010
Last updated
2 Feb 2023
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 18309951

  • 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.

    PubMed 19097774

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KX2-391 in people with Bone-Metastatic, Castration-Resistant Prostate Cancer, run by Athenex, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients who do not have clinical or radiographic progression (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01074138, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in