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

NCT02805894 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: NBTXR3-104
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose and early Dose Limiting Toxicities (DLT) of NBTXR3

  24 months

• Recommended Dose(s) of NBTXR3

  24 months

Study Arms (2)

NBTXR3 activated by IMRT only

EXPERIMENTAL

Part I Dose Escalation NBTXR3 will be administered by intra-prostate injection and then activated 10 days later by: \- EBRT delivered as 45 Gy in 25 fractions of 1.8 Gy each; to the prostate and seminal vesicles, followed by 34.2 Gy in 19 fractions to the prostate and proximal seminal vesicles , over 9-10 weeks, utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT A)

Drug: NBTXR3 activated by IMRT only

NBTXR3 activated by Brachytherapy & IMRT

EXPERIMENTAL

Part I Dose Escalation NBTXR3 will be administered by intra-prostate injection and then activated 10 days later by: \- Brachytherapy Boost and EBRT delivered as a single fraction of 15 Gy in one day to the prostate by High Dose Rate Brachytherapy followed by EBRT (initiated within 2-4 weeks after completion of Brachytherapy), delivered as 45 Gy in 25 fractions of 1.8 Gy to the prostate and seminal vesicles utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT B)

Drug: NBTXR3 activated by Brachytherapy & IMRT

Interventions

NBTXR3 activated by IMRT only DRUG

Single local administration of NBTXR3 by injection into the prostate gland prior to the IMRT treatment

Also known as: Hafnium Oxide nanoparticles

NBTXR3 activated by IMRT only

NBTXR3 activated by Brachytherapy & IMRT DRUG

Single local administration of NBTXR3 by injection into the prostate gland prior to the Brachytherapy \& IMRT treatment

Also known as: Hafnium Oxide nanoparticles

NBTXR3 activated by Brachytherapy & IMRT

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nanobiotix: lead

Study Sites (2)

Dana Farber Cancer Institute/Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Adam Dicker, MD

  Thomas Jefferson University Hospital Philadelphia, PA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 20, 2016
• Study Start: November 15, 2017
• Primary Completion: March 19, 2020
• Study Completion: March 19, 2020
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)