NBTXR3 Nanoparticles and EBRT or EBRT With Brachytherapy in the Treatment of Prostate Adenocarcinoma

• Status: Terminated
• Trial end date: 2020-03-19
• Target enrollment: 0
• Participant gender: Male

Summary

This study is a Phase 1/2 open-label involving 2 groups of patients newly diagnosed with either unfavorable intermediate risk or high risk prostate adenocarcinoma. One group will receive only EBRT and the other group will receive a Brachytherapy boost and EBRT. Both groups will receive treatment with androgen deprivation. There will be 2 consecutive steps, a dose escalation and a subsequent dose expansion part.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nanobiotix

Criteria

Inclusion Criteria:

• Age ≥ 18

• Histologically confirmed adenocarcinoma of the prostate gland by needle core samples with assigned Gleason score

• Subjects ADT naive or subjects who are already on ADT treatment and scheduled to receive radiation therapy for their adenocarcinoma of prostate are eligible. An 8-week course of ADT is required to be completed prior to NBTXR3 administration and initiation of radiation therapy.

• Pelvic and para-aortic lymph nodes must be negative on CT-scan or MRI of the abdomen and pelvis performed within 12 weeks prior to enrollment into the study

• Prostate adenocarcinoma with High Risk (HR) and Unfavorable Intermediate Risk (UIR) for recurrence classification as determined by one of the following combinations:

• High risk (HR): subjects with one or more of the following risk factors:

• Clinical stage: T3/T4

• Gleason score (GS): 8-10

• PSA > 20

• N0

• Unfavorable Intermediate Risk (UIR): subjects with no HR features but with one or more of the following adverse risk factors:

• At least 2 of the following 3 factors: Gleason score(GS) 3+4=7 and/or PSA 10-20 and/or T2b/c

• Gleason score (GS) 4+3=7

• Greater than 50% of biopsy cores positive and at least one other risk factor:

Gleason score (GS) 7 and/or PSA 10-20 and/or T2b/c

• No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if bone CT or MRI of hot spots are negative for metastasis

• Baseline serum PSA value performed with an FDA-approved assay within 120 days prior to registration. Study entry PSA should not be obtained within 10-day period following prostate biopsy or following initiation of hormonal therapy

• ECOG performance status must be 0 or 1

• Adequate function of bone marrow:

• Hemoglobin > 100 g/L

• Absolute Neutrophils > 1.5 x 109/L

• Platelets > 100 x 109/L,

• Adequate function of kidney:

• Serum creatinine < 1.5 x ULN

• Adequate function of liver:

• AST ≤ 3.0 x ULN

• ALT ≤ 3.0 x ULN

• Total bilirubin ≤ 1.5 x ULN

• Non-Childbearing Potential: Male subjects and their partners must meet one of the following criteria to be considered of non-childbearing potential:

• Males have undergone sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate, or

• Heterosexually active males and their partners of childbearing potential must agree or use at least 2 forms of highly effective methods of contraception, including at least 1 barrier method. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of <1% per year when used consistently and correctly (i.e., perfect use). Contraception must include male condom or female condom used with a spermicide (i.e., foam, gel, film, cream, suppository) as well as established use of oral, injected or implanted hormonal methods of contraception, correctly placed intrauterine device or intrauterine system.

Exclusion Criteria:

• Written Informed Consent not obtained, signed and dated

• History of colorectal surgery, or repeated endoscopic examinations/interventions related to anorectal diseases or proximal urethral stricture requiring dilatation

• Prostate size volume ≥90 cc

• Brachytherapy with EBRT in subjects whose prostate volume is >60cc

• Severe, active co-morbidity, defined as follows:

• Inflammatory bowel disease, active rectal diverticulitis, Crohn's disease affecting the rectum, anal stenosis or ulcerative colitis. (Nonactive diverticulitis and Crohn's disease not affecting the rectum are allowed)

• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months

• Myocardial infarction within the last 6 months

• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization

• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC (Centers for Disease Control) definition

• Prior invasive malignancy, except non-melanoma skin cancer, carcinoma in-situ of the bladder or head and neck region, unless disease free for a minimum of 2 years

• Subjects with congenital long QT syndrome or subjects taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. subjects with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events

• Uncontrolled lung disease

• Subjects with any evidence of distant metastases

• subjects with any contraindication to pelvic radiotherapy including, but not limited to, previous pelvic radiotherapy or brachytherapy

• Presence of bilateral hip replacement prostheses

• Hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist or oral anti-androgen) exceeding 4 months prior to registration

• Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician

• Complete initial work up earlier than 12 weeks prior to subject registration

• Subjects unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

• Subjects participating in another clinical investigation at the time of signature of the informed consent.