A Study of Dovitinib With Androgen Deprivation Therapy (ADT) in Patients With Metastatic Prostate Cancer Receiving Primary ADT

NCT02065323 | Withdrawn Phase 2 DMC

• 2 other identifiers: CCCN-PC1301CTKI258AUS18T
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate if adding the investigational drug Dovitinib to standard androgen ablation therapy (ADT) is beneficial in prolonging the time to disease progression in patients with metastatic prostate cancer who are receiving ADT for the first time. Dovitinib belongs to the class of drugs known as tyrosine kinase receptor inhibitors. Tyrosine kinase receptor inhibitors have been shown to have anti-tumor effects and inhibit new blood vessel formation. New blood vessel development is necessary for the growth and spread of certain tumors, such as prostate cancer. It is thought that by inhibiting new blood vessel formation, any existing or new tumors may be unable to grow. Dovitinib targets existing cancer cells and also works to stop the formation of new blood vessels. Patients will be randomly assigned to received ADT alone or ADT plus Dovitinib. ADT will be administered per standard of care. Dovitinib will be taken by mouth once daily for 5 continuous days, followed by 2 days with no Dovitinib. This schedule will repeat and continue until disease progression or removal from treatment for other reasons. Participants may start ADT prior to entering the study; however, treatment with Dovitinib must begin no later than 120 days from the start of ADT. Participants will be asked to donate blood samples for research purposes; this is an optional part of the study. Research on blood samples will study circulating tumor cells and certain biomarkers (proteins on cells) to increase the understanding of prostate cancer and explore if certain biomarkers can help predict how tumors will react to treatment. Samples of existing tumor tissue will also be examined for research purposes.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Metastatic; Hormone-sensitive; Androgen Deprivation Therapy (ADT); Castration-Resistant Prostate Cancer (CRPC); Dovitinib; TKI258; Circulating Tumor Cells

Outcome Measures

Primary Outcomes (1)

• Time to onset of castration resistant prostate cancer (CRPC)

  CRPC defined as documented presence of two of the following criteria: PSA progression, radiographic progression, and/or symptomatic deterioration due to prostate cancer.

  Every 12 weeks from the start of treatment until the date of first documented progression, up to 24 months.

Secondary Outcomes (6)

• Effect on predictive PSA benchmarks

  PSA measured at baseline and every 12 weeks until the date of first documented progression, up to 24 months.

• Overall survival

  From date of randomization until date of death, or patient lost to follow up. Survival will be assessed at least every 4 weeks during treatment and every 6 months after disease progression up to 5 years.

• Radiographic response rate and progression free survival in patients with measurable disease.

  Radiographic evaluations occur at baseline and every 12 weeks while on study until date of first documented disease progression, up to 24 months.

• Adverse event frequency

  Assessed every 2 weeks for first 8 weeks, then every 4 weeks while on study and at 30 days following last dose of dovitinib, up to 24 months.

• Changes in circulating tumor cell counts

  Baseline and every 3 months while on study until date of first documented progression, up to 24 months.

Other Outcomes (4)

• Exploratory: Pharmacodynamic effect on plasma biomarkers

  Baseline and every 3 months while on study until date of first documented progression, up to 24 months.

• Exploratory: Archival tissue expression of biomarkers and mutations related to dovitinib mechanism of action and correlation with clinical outcome

  Baseline one-time.

• Exploratory: Circulating Tumor Cell expression of biomarkers and mutations related to dovitinib mechanism of action and correlation with clinical outcome

  Baseline and every 3 months while on study until date of first documented progression, up to 24 months.

Study Arms (2)

ADT alone

ACTIVE COMPARATOR

Standard androgen deprivation therapy (LHRH analogue or orchiectomy)

Drug: Standard ADT

ADT plus Dovitinib

EXPERIMENTAL

Standard androgen deprivation therapy (LHRH analogue or orchiectomy) Dovitinib 500 mg/day given on a five-days-on-two-days-off schedule. One cycle equals 28 days. Cycles will repeat continuously until disease progression, or removal from study for other reasons.

Drug: Standard ADT; Drug: Dovitinib

Interventions

Standard ADT DRUG

Standard androgen deprivation therapy with either continually dosed LHRH agonist or antagonist, or achieved via bilateral orchiectomy.

ADT alone; ADT plus Dovitinib

Dovitinib DRUG

Dovitinib 500 mg/day given on a five-days-on-two-days-off schedule. One cycle equals 28 days. Cycles will repeat continuously until disease progression, or removal from study for other reasons.

Also known as: TKI258

ADT plus Dovitinib

Eligibility Criteria

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

You may qualify if:

• Men with metastatic hormone-sensitive metastatic prostate cancer
• ECOG (WHO) performance status 0-2
• Age ≥ 18 years old
• PSA \> 4.0
• Patients must have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) \> 9 g/dL
• Serum total bilirubin: ≤ 1.5 x ULN
• ALT and AST ≤ 3.0 x ULN (for patients with or without liver metastases)
• Serum creatinine ≤ 1.5 x ULN or serum creatinine \> 1.5 - 3 x ULN if calculated creatinine clearance (CrCl) is ≥ 30 mL/min using the Cockroft-Gault equation
• Urine dipstick reading negative for proteinuria, or if 1+, then total urinary protein must be less than 500 mg and measured creatinine cleaners ≥ 50 mL/min/1.73m2 from a 24 hour urine collection
• Histologically or cytologically confirmed prostate cancer.
• Urine dipstick reading negative for proteinuria, or, if documentation of +1 results for protein on dipstick reading, then total urinary protein ≤ 500 mg and measured creatinine clearance ≥ 50 mL/min/1.73m2 from a 24 hour urine collection.
• Patients may have begun hormonal therapy, but must have done so within 120 days of study treatment.

You may not qualify if:

• Patients with brain metastases
• Patients with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer (such as basal cell carcinoma, squamous cell carcinoma, or non-melanomatous skin cancer)
• Patients who have received prior cytotoxic chemotherapy within 3 years of starting study drug.
• Patients who have received targeted therapy (e.g., sunitinib, sorafenib, pazopanib) ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy.
• Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g., for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities.
• Patients who have undergone major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury.
• Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases
• Neurological compromise or dysfunction due to metastases
• Ureteral or bladder outlet obstruction due to metastases or local invasion
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Patients who are currently receiving anticoagulation treatment with therapeutic doses of warfarin
• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol

Sponsors & Collaborators

• Oscar Goodman, Jr.: lead
• Comprehensive Cancer Centers of Nevada: collaborator

Study Sites (1)

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89148, United States

Location

Related Publications (5)

• Goodman OB Jr, Febbraio M, Simantov R, Zheng R, Shen R, Silverstein RL, Nanus DM. Neprilysin inhibits angiogenesis via proteolysis of fibroblast growth factor-2. J Biol Chem. 2006 Nov 3;281(44):33597-605. doi: 10.1074/jbc.M602490200. Epub 2006 Aug 28.

  PMID: 16940054 BACKGROUND

• Horiguchi A, Zheng R, Goodman OB Jr, Shen R, Guan H, Hersh LB, Nanus DM. Lentiviral vector neutral endopeptidase gene transfer suppresses prostate cancer tumor growth. Cancer Gene Ther. 2007 Jun;14(6):583-9. doi: 10.1038/sj.cgt.7701047. Epub 2007 Apr 6.

  PMID: 17415380 BACKGROUND

• Horiguchi A, Chen DY, Goodman OB Jr, Zheng R, Shen R, Guan H, Hersh LB, Nanus DM. Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis. Prostate Cancer Prostatic Dis. 2008;11(1):79-87. doi: 10.1038/sj.pcan.4500984. Epub 2007 Jun 12.

  PMID: 17563767 BACKGROUND

• Goodman OB Jr, Symanowski JT, Loudyi A, Fink LM, Ward DC, Vogelzang NJ. Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2011 Sep;9(1):31-8. doi: 10.1016/j.clgc.2011.04.001. Epub 2011 Jun 25.

  PMID: 21705286 BACKGROUND

• Mitra R, Chao OS, Nanus DM, Goodman OB Jr. Negative regulation of NEP expression by hypoxia. Prostate. 2013 May;73(7):706-14. doi: 10.1002/pros.22613. Epub 2012 Nov 8.

  PMID: 23138928 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis; Neoplastic Cells, Circulating

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Oscar B Goodman, Jr., MD, PhD

  Comprehensive Cancer Centers of Nevada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician, Comprehensive Cancer Centers of Nevada; Professor of Pharmaceutical Sciences, Roseman University of Health Sciences

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 19, 2014
• Primary Completion: August 1, 2014
• Last Updated: January 19, 2015

Record last verified: 2015-01

Locations

US (1)