PLX3397, Radiation Therapy, and Antihormone Therapy in Treating Patients With Intermediate- or High-Risk Prostate Cancer

NCT02472275 | Completed Phase 1 DMC

• 4 other identifiers: 2014-075NCI-2015-007421501013723P30CA022453
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I trial studies the side effects and best dose of multitargeted tyrosine kinase inhibitor PLX3397 (PLX3397) when given together with radiation therapy and antihormone therapy in treating patients with prostate cancer that is at intermediate or high risk of spreading. Multitargeted tyrosine kinase inhibitor PLX3397 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may also help the radiation therapy work better. Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin acetate, or degarelix, may lessen the amount of androgens made by the body. Giving multitargeted tyrosine kinase inhibitor PLX3397 with radiation therapy and antihormone therapy may be a better treatment for prostate cancer.

Conditions

Stage I Prostate Adenocarcinoma; Stage II Prostate Adenocarcinoma; Stage III Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Grade of specific types of toxicity

  Frequency distributions will be generated by dose level, and overall.

  Up to 30 days after end of study treatment

• MTD of multitargeted tyrosine kinase inhibitor PLX3397, determined according to incidence of DLT

  4 months

Secondary Outcomes (3)

• Change in metabolic syndrome parameters

  Baseline to month 7

• Change in PSA levels

  Baseline to up to month 7

• Change TAM levels as measured by immunohistochemistry

  Baseline to month 2

Study Arms (1)

Treatment (PLX3397, radiation therapy, ADT)

EXPERIMENTAL

Patients receive multitargeted tyrosine kinase inhibitor PLX3397 PO BID for 6 months, undergo radiation therapy for 2 months daily (Monday-Friday) beginning at month 3, and undergo ADT with leuprolide acetate, goserelin acetate, or degarelix injections in any month.

Drug: Antiandrogen Therapy; Other: Laboratory Biomarker Analysis; Drug: Multitargeted Tyrosine Kinase Inhibitor PLX3397; Radiation: Radiation Therapy

Interventions

Antiandrogen Therapy DRUG

Undergo ADT with leuprolide acetate, goserelin acetate, or degarelix

Also known as: ADT, Androgen Deprivation Therapy, Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation Therapy

Treatment (PLX3397, radiation therapy, ADT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (PLX3397, radiation therapy, ADT)

Multitargeted Tyrosine Kinase Inhibitor PLX3397 DRUG

Given PO

Also known as: PLX3397

Treatment (PLX3397, radiation therapy, ADT)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (PLX3397, radiation therapy, ADT)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed diagnosis of prostate adenocarcinoma
• Must have confirmed viable archival prostate biopsy tissue available as per Section 8.1 (this will be collected for patients going on study after the MTD has been reached
• Intermediate or high risk prostate cancer patients who are candidates for radiation therapy:
• Gleason \>7 or
• Clinical or pathological \> T2b disease or
• PSA \> 10 ng/mL
• No evidence of metastatic disease by clinical and radiological staging
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
• No standard contraindications to radiation therapy including prior significant radiation therapy, inflammatory bowel disease, irritable bowel syndrome or collagen vascular disease
• Prior history of up to 8 weeks of androgen deprivation therapy defined as lutenizing-hormone releasing hormone (LHRH) or other medical castration therapy prior to registration is acceptable. This will be in addition to the 6 months of ADT on study.
• Life expectancy of at least 3 months
• Adequate hematologic, hepatic, and renal function as defined by:
• Absolute neutrophil count ≥ 1.5 × 109/L
• Hemoglobin \> 10 g/dL
• Platelet count ≥ 100 × 109/L

You may not qualify if:

• Investigational drug use within 28 days of the first dose of PLX3397 or concurrently
• At Screening QTcF ≥450 msec
• Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results
• Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption of study drug
• Known active or chronic human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection and with normal liver function (ALT, AST, total and direct bilirubin ≤ ULN) is allowed.
• Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if TBil is ≤ 1.5 × ULN.
• Active cancer (either concurrent or within the last 3 years) that requires nonsurgical therapy (e.g. chemotherapy or radiation therapy), with the exception of surgically treated basal or squamous cell carcinoma of the skin, or melanoma insitu.
• AST/ALT \> 2.5X ULN or \>5X ULN in the presence of liver metastases.
• Current treatment with anti-androgen is allowed for a maximum of one month to prevent flare response with ADT
• Concomitant use of acid reducing agents (e.g., proton pump inhibitors, H2 receptor antagonists, antacids)
• Concomitant use of strong and moderate CYP3A4 inhibitors and inducers
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of the study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Karmanos Cancer Institute at McLaren Northern Michigan - Petoskey Radiation Oncology

Petoskey, Michigan, 49770, United States

Location

Karmanos Cancer Institute at McLaren Northern Michigan- Petoskey Medical Oncology

Petoskey, Michigan, 49770, United States

Location

MeSH Terms

Interventions

Androgen Antagonists; pexidartinib; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutics; Physical Phenomena

Study Officials

• Elisabeth I. Heath, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 15, 2015
• Study Start: June 1, 2015
• Primary Completion: August 5, 2019
• Study Completion: August 5, 2019
• Last Updated: October 6, 2020

Record last verified: 2020-10

Locations

US (3)