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

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oscar Goodman, Jr.
• Collaborator: Comprehensive Cancer Centers of Nevada
• Treatments: Androgens; Ascorbic Acid; Estrogens, Conjugated (USP); Methyltestosterone

Criteria

Inclusion Criteria:

• 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.

• Patients must have metastatic disease (extensive or limited).

• Scans (CT chest, abdomen, and pelvis) and bone scan must be obtained within 4 weeks of treatment.

• Written informed consent obtained according to local guidelines

Exclusion Criteria:

• 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

• Rising PSA meeting criteria for progression to CRPC

• Patients unwilling or unable to comply with the protocol