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Prostate CancerPhase 2NCT00831792

TKI258 in Castrate Resistant Prostate Cancer

A Phase 2 study testing TK1258 in people with Prostate Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

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

Official record
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Trial summary

The goal of this clinical research study is to learn if a decrease in the levels of prostate specific antigen (PSA) may be linked with the status of prostate cancer that has spread to the bones. Read more about this study

Who is it for?
Any age, men only
Conditions the study is for
Prostate Cancer
What is being tested?
TK1258
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
7 Apr 2010to 12 Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 2. (Karnofsky Performance Status >/= 50%)
  • Serum testosterone levels </= 50ng/ml
  • Ongoing gonadal androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study.
  • Progression of disease despite androgen ablation (either documented osseous or soft tissue metastatic disease progression or by PSA criteria progression). a)Definition of Progressive disease by PSA evidence: a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. The participant will need a baseline test and a test to show that the PSA has increased.
  • Discontinue diethylstilbestrol (DES) for >/= 4 weeks and antiandrogens >/= 6 weeks prior to study drug.
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  • Discontinue any steroids prescribed to specifically treat prostate cancer (for e.g as a secondary hormonal manipulation or for cord compression) >/= 4 weeks prior to study drug. Steroids chronically prescribed for a non-cancer-related illness (e.g. asthma or COPD) that is well controlled with medical management are permissible to an equivalent of < 10 mg Prednisone daily.
  • Antiandrogen Withdrawal: Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen. Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression.
  • For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
  • For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation
  • Laboratory Requirements: 1) Adequate adrenal function (absence of symptoms or electrolyte imbalances that indicate adrenal insufficiency); 2) White blood cell count (WBC) count >/= 3,000/microl; 3) Absolute Neutrophil Count (ANC) >/= 1,500/microl; 4) Hemoglobin >/= 8.0 g/dL independent of transfusion; 5) Platelet count >/= 75,000/microL; 6) Serum albumin >/= 3.0 g/dL; 7) Serum creatinine < 1.5 x ULN or a calculated creatinine clearance > 60 mL/min (as calculated by Cockcroft-Gault method) 8) Serum potassium >/= 3.5 mmol/L
  • No evidence of chronic or acute DIC (Disseminated Intravascular Coagulation) or bleeding tendency and no angina at rest.
  • Patient must be willing and able to comply with protocol requirements. All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must also have signed an authorization for the release of their protected health information.

Who cannot join

  • Histologic variants other than adenocarcinoma in the primary tumor
  • Abnormal liver functions consisting of any of the following: a) Serum bilirubin >/= 1.5 * upper limit of normal (ULN) b) AST and ALT > 2.5 * ULN
  • Therapy with other hormonal therapy, including any dose of Ketoconazole, finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (eg, Saw Palmetto and PC-SPES) within 4 weeks of study drug.
  • Requirement for corticosteroids greater than the equivalent of 7.5 mg of prednisone daily.
  • Therapy with samarium or strontium within 8 weeks prior to first dose of study drug.
  • Active infection or concomitant illness that is not controlled with medical management.
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  • Prior radiation therapy completed < 4 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
  • Any currently active second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.
  • Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
  • Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study
  • Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)
  • Acute or chronic hepatitis B or C
  • Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 4-week washout period before treatment initiation
  • Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study drug. Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy during the study.
  • Impaired cardiac function or clinically significant cardiac diseases, including any of the following: a.) History or presence of serious uncontrolled ventricular arrhythmias or presence of atrial fibrillation; b.) Clinically significant resting bradycardia (< 50 beats per minute); c.) Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher);
  • (# 13 Conti'd) Any of the following within 6 months prior to study entry: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE); e.) Uncontrolled hypertension defined by an SBP>150 and/or a DBP>100 mm Hg with or without anti-hypertensive medication; f.) Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month.
  • History of pituitary or adrenal dysfunction
  • History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
  • Prior therapy with TKI258
  • Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 3.0) grade of </= 1. Chemotherapy induced alopecia and grade 2 neuropathy is allowed.
  • Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study.
  • Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 8 weeks after the end of study treatment. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: An Observational Study of Continuous TKI258, in Castration-Resistant Prostate Cancer Patients Evaluating Markers of FGF Signaling in Bone Marrow Plasma

The goal of this clinical research study is to learn if a decrease in the levels of prostate specific antigen (PSA) may be linked with the status of prostate cancer that has spread to the bones. Researchers also want to learn how changes in your blood PSA level might affect the rebuilding of healthy bones while you are being treated with TKI258 for prostate cancer.

Read the detailed description

The Study Drug:

TKI258 is designed to perform several anti-tumor functions, including cutting off the blood supply to tumors. Researchers think this may help slow or stop the growth of prostate cancer.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 4 capsules of TKI258 1 time each day for 5 days in a row followed by 2 days of rest (Days 1-5, 8-12, 15-19, and 22-26 of each 28-day study "cycle"). You should take the TKI258 capsules with about 8 ounces of water and at least 1 hour before a meal (breakfast) or at least 2 hours following a meal (breakfast). If you want, you may take the drug with a meal that has fewer than 500 calories and 20 grams of fat.

Study Visits:

Every 28 days makes up 1 study "cycle."

On Day 1 of Cycle 1 and all cycles after that, the following tests and procedures will be performed:

  • Your complete medical history will be recorded.
  • You will be asked about any drugs or treatments you may be receiving.
  • You will be asked about any side effects you may have experienced.
  • You will have a physical exam, including measurement of your vital signs and weight.
  • Your performance status will be evaluated.
  • Blood (about 2 tablespoons) will be collected for routine tests. This blood will also be tested to measure your PSA.
  • You will have a triplicate ECG (3 ECGs in a row) before you take the study drug. You will also have 1 ECG about 6 hours after you take the study drug.

On Day 12 (+/- 3 days) of Cycles 1 and 2, and day 26 of Cycle 1 (+/- 3 days) blood (about 1 tablespoon) will be collected for routine tests. Part of the Cycle 2 blood draw will be used to measure the amount of TKI258 in your system. Note that the Day 26 of Cycle 1 visit could end up being scheduled on the same day as the Day 1 of Cycle 2 visit described above.

On Day 1 of Cycle 2 and every odd numbered Cycle after this (Cycles 3, 5, 7and so on), the following tests and procedures will be performed:

  • Blood (about 2 teaspoons) will be collected for routine tests.
  • Urine will be collected to test for markers relating to your bone.

At the end of every cycle (about Day 26), you will have an ECG.

Every 3 Cycles (about every 12 weeks), the following tests and procedures will be performed:

  • Blood (about 1 teaspoon) will be drawn to measure your levels of heart enzymes
  • You will have an echocardiogram or MUGA scan like the one you had at the screening visit to check your heart function.

About 7-10 weeks after your first dose of study drug, you will have another bone marrow biopsy and aspiration performed to check the status of the disease and for biomarker testing.

CT and/or bone scans will be performed every 8 weeks for the first 6 months and every 3 months after that to check the status of the disease.

Length of Study:

You may remain on study for as long as you are benefiting. You will be taken off study if intolerable side effects occur or if the disease gets worse.

End-of-Study Visit:

Within 4 weeks after your last dose of the study drug, you will return to the clinic for an end-of-study visit. The following tests and procedures will be performed:

  • You will have a physical exam, including measurement of your vital signs, and weight.
  • Your performance status will be evaluated.
  • You will be asked about any drugs or treatments you may be receiving.
  • You will be asked about any side effects you have experienced since you last visit.
  • Blood (about 3 tablespoons) and urine will be collected for routine tests. This blood will also be tested to measure certain hormones, heart enzymes, and PSA.
  • You will have a chest x-ray, bone scan, and either a computed tomography (CT) or magnetic resonance imaging (MRI) scan of your abdomen and pelvis to check the status of the disease.
  • You will have an ECG and either an echocardiogram or a MUGA scan.
  • You will have a bone marrow biopsy and aspiration performed to check the status of the disease and for biomarker testing.

Long-Term Follow-up:

Once you are no longer on this study, the research staff will check up on you about every 3 months. This update will consist of a phone call, an e-mail, or a review of your medical and/or other records. You will not have any extra tests, procedures, or study visits. If contacted by phone, the call would only last about 5 minutes.

This is an investigational study. TKI258 is not FDA approved or commercially available. It is being used in this study for research purposes only.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Prostate Cancer
Being tested
TK1258
Keywords
Prostate Cancer, Advanced Prostate Cancer, Castrate Resistant Prostate Cancer, Prostate Specific Antigen, PSA, Castration-Resistant Prostate Cancer Patients, TK1258, CHIR-258
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • TK1258Drug

    Also called CHIR-258

    4 capsules (100 mg/capsules) of TKI 258 by mouth once daily (total of 400 mg of TKI258 per day).

Study groups in NCT00831792
Study groupRoleWhat they receive
TK1258Experimental4 capsules (100 mg/capsules) of TKI 258 by mouth once daily (total of 400 mg of TKI258 per day). Following an initial 4-week cycle at a starting dose of 400 mg 5 days- on and 2 days off, TKI258 may be escalated to 500 mg/day 5 days-on/2 days off if no significant Grade3/4 AEs or laboratory abnormalities are observed.
Receives: Drug: TK1258

What is being measured

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

  1. The Number of Participants With Improvement, Disease Progression or Stable Disease

    Three consecutive PSA elevations above nadir or baseline are required for progression. Each increment in PSA should be a minimum of 1 ng/ml and at least 2 weeks apart or will not count. The time of PSA progression will be taken as the time of the first of these PSA elevations that represents an increment by at least 25% above the nadir or baseline. Given that increments in PSA do not always represent treatment failure, particularly when novel agents with uncertain effects on PSA levels are being evaluated, clinical and radiological correlation is recommended at the discretion of the treating physician. In patients with PSA progression alone without clinical or radiological evidence of disease progression, continued therapy on study is at the discretion of the treating physician in consultation with the principal investigator.

    Measured: From the time of enrollment until 30 days beyond the date of the last study drug administration

Timeline

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

  1. First posted29 Jan 2009 (estimated)
  2. Study start7 Apr 2010
  3. Primary completion12 Jun 2017
  4. Study completion12 Jun 2017

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
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00831792
Sponsor's protocol ID
2008-0510
Other IDs
NCI-2011-01106
Status last verified
Aug 2019
First submitted
27 Jan 2009
Last updated
11 Sep 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TK1258 in people with Prostate Cancer, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 22 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 11 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 11 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Number of Participants With Improvement, Disease Progression or Stable Disease (time frame: From the time of enrollment until 30 days beyond the date of the last study drug administration). 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 NCT00831792.

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 11 Sep 2019.

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