Rectal Hydrogel Spacer for Prostate Cancer

(FIRST STAR Trial)

Overseen By Andrea DeAbreu

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Anticoagulants

Disqualifiers: Castrate resistance, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6-8 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to reduce bowel problems in prostate cancer patients undergoing a second round of radiation treatment. The treatment involves placing a biodegradable gel, called SpaceOAR (or Rectal Hydrogel Spacer), between the prostate and rectum to shield the rectum from radiation. This approach may improve patients' comfort and quality of life by reducing radiation side effects. Individuals whose prostate cancer has returned after initial radiation treatment and who are willing to participate may be suitable for this trial. As an unphased study, this trial allows participants to contribute to innovative research that could enhance future treatment options.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on anticoagulation medication and it's unsafe to discontinue, you may be excluded from the trial.

What prior data suggests that this hydrogel spacer is safe for reducing rectal toxicity in prostate cancer patients?

Research shows that using a hydrogel spacer, such as SpaceOAR, is generally safe for patients undergoing radiation therapy for prostate cancer. Studies indicate that these spacers can reduce harm to the rectum after radiation. For example, one review found a very low complication rate of just 0.96% with hydrogel spacers, and importantly, no severe gastrointestinal problems were reported.

A hydrogel spacer can result in less radiation reaching the rectum, leading to fewer side effects and better bowel health over time. Patients who used SpaceOAR during radiation therapy experienced fewer significant declines in their bowel quality of life. Overall, evidence suggests that SpaceOAR is well-tolerated and helps protect the rectum during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about SpaceOAR because it offers a unique approach to protecting the rectum during prostate cancer treatment. Unlike traditional methods that rely on precise radiation techniques to minimize damage, SpaceOAR involves placing a hydrogel spacer between the prostate and rectum. This spacer physically separates the two organs, reducing the risk of radiation hitting the rectum and potentially improving bowel quality of life for patients. By minimizing radiation exposure to healthy tissue, SpaceOAR aims to decrease side effects and enhance the overall treatment experience for prostate cancer patients.

What evidence suggests that this hydrogel spacer is effective for reducing rectal toxicity in prostate cancer treatment?

Research has shown that using a hydrogel spacer like SpaceOAR, which participants in this trial will receive, can reduce rectal damage during prostate cancer radiation therapy. Studies have found that these spacers decrease the radiation reaching the rectum, resulting in fewer side effects such as bowel problems. For patients undergoing radiation, this leads to a better quality of life with fewer post-treatment issues. Specifically, one study found that patients using the hydrogel spacer experienced less decline in bowel, urinary, and sexual health compared to those who did not use it. Overall, these spacers offer a promising way to make radiation treatment safer and more comfortable for prostate cancer patients. ^{1 2 3 4 5}

Who Is on the Research Team?

Amandeep Taggar, MD

Principal Investigator

Sunnybrook

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer that has come back locally and can be seen on scans. They must be able to fill out health questionnaires and agree to join the study. Men are excluded if they have resistant cancer, spread of cancer outside the pelvis, previous high-dose radiation therapy, bleeding disorders, poor urinary function, MRI contraindications or cannot stop blood thinners safely.

Inclusion Criteria

Able and willing to complete EPIC and EQ-5D questionnaires

My prostate cancer has come back in the same area and has been confirmed by tests.

Willing to give informed consent to participate in this clinical trial

Exclusion Criteria

My prostate cancer is resistant to hormone therapy, with a PSA > 3 ng/ml and low testosterone.

I have been diagnosed with a bleeding disorder.

I have had intense radiotherapy with doses of 5Gy or more per session.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Hydrogel Spacer Placement

Placement of a hydrogel spacer between the prostate and rectum to decrease toxicity and improve bowel quality of life

1 week

1 visit (in-person)

Treatment

Participants undergo hypofractionated external beam radiotherapy (SABR) for re-irradiation of locally recurrent prostate cancer

6-8 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life using IPSS, EPIC, and EQ-5D scores

5 years

What Are the Treatments Tested in This Trial?

Interventions

• SpaceOAR

Trial Overview The trial tests a biodegradable gel called SpaceOAR placed between the prostate and rectum during salvage SABR (a type of focused radiation therapy) to reduce bowel side effects and improve quality of life in patients undergoing re-irradiation for recurrent prostate cancer.

How Is the Trial Designed?

Group I: Study Arm Experimental Treatment 1 Intervention

All patients with local recurrence of prostate cancer post irradiation will undergo placement of a hydrogel spacer between the prostate and rectum, in an effort to decrease toxicity and improve patient's bowel quality of life prior to SABR.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

The engineered 3D hydrogel system successfully supports the co-culture of prostate cancer patient-derived xenograft (PDX) cells and osteoblastic cells, effectively mimicking the tumor-stromal interactions found in bone metastasis.

This model not only maintains cell viability and the osteogenic phenotype of PDX cells but also demonstrates that the interaction between prostate cancer cells and osteoblasts promotes cancer progression, making it a valuable tool for studying prostate cancer bone metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions. Fong, EL., Wan, X., Yang, J., et al.[2022]

In a study involving nude mice, LNCaP human prostate cancer cells mixed with gelatin sponges (VETSPON) resulted in 100% tumor incidence, while only 70% of those mixed with Matrigel developed tumors, indicating that VETSPON is more effective in supporting tumor growth.

Tumors formed in VETSPON showed less variability in volume and promoted better cell survival at early stages compared to Matrigel, suggesting that gelatin sponges may be a superior choice for modeling prostate cancer in preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemostatic gelatin sponge is a superior matrix to matrigel for establishment of LNCaP human prostate cancer in nude mice. Cui, L., Chen, P., Tan, Z., et al.[2021]

SpaceOAR® hydrogel injection is a safe and minimally invasive outpatient procedure for creating space between the prostate and rectum before radiotherapy, with a very low complication rate observed in 58 patients.

The procedure has a short learning curve for healthcare providers with adequate ultrasound experience, making it feasible to implement in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First experience in the Czech Republic with perirectal hydrogel injection before radiotherapy for prostate cancer. Vik, V., Novotný, T., Lukeš, M., et al.[2021]

An injectable hydrogel made from hydrolyzed collagen shows promise as a regenerative matrix for patients after radical prostatectomy, adapting to tissue shapes and promoting healing without affecting nerve growth.

The hydrogel can also deliver a chemotherapeutic drug that inhibits harmful cell growth while preserving the health of nerve cells, suggesting it could help prevent complications like fibrosis and tumor relapse after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate carcinoma cell growth-inhibiting hydrogel supports axonal regeneration in vitro. Franke, K., Baur, M., Daum, L., et al.[2013]

The study developed a patient-derived xenograft (PDX) model of bone metastatic prostate cancer using immunocompromised mice, which better mimics the disease compared to traditional cell lines.

Encapsulating PDX tumor cells in a three-dimensional hyaluronan-based hydrogel preserved cell viability and androgen receptor expression, allowing for more accurate drug sensitivity testing, such as the differential response to docetaxel compared to standard cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening. Fong, EL., Martinez, M., Yang, J., et al.[2021]

The use of the hydrogel spacer SpaceOAR significantly reduced the incidence of low-grade diarrhoea and proctitis in prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT), with 21.4% of patients without SpaceOAR experiencing low-grade diarrhoea compared to only 6.2% with it.

Patients with SpaceOAR also had a lower cumulative incidence of proctitis (26.7% vs 9.2% for grades G1 and G2), indicating that the spacer effectively minimizes rectal toxicity associated with radiotherapy for up to 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late toxicities of prostate cancer radiotherapy with and without hydrogel SpaceAOR insertion. Te Velde, BL., Westhuyzen, J., Awad, N., et al.[2020]

The SpaceOAR® hydrogel system, designed to protect the rectum during prostate radiotherapy, can potentially cause rectal toxicity, as evidenced by a case where a 75-year-old man developed a rectal ulcer after its insertion.

Post-implant magnetic resonance imaging (MRI) was effective in detecting hydrogel infiltration into the rectum, suggesting that MRI could be a valuable follow-up tool to monitor for complications related to SpaceOAR® hydrogel use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous remission of rectal ulcer associated with SpaceOAR® hydrogel insertion in radiotherapy for prostate cancer. Imai, K., Sakamoto, H., Akahane, M., et al.[2022]

The SpaceOAR hydrogel spacer is a safe and well-tolerated procedure with a 99% technical success rate, effectively creating over 1 cm of space between the prostate and rectum, which significantly reduces rectal radiation exposure during prostate cancer treatment.

Patients receiving the hydrogel spacer experienced lower rates of acute and long-term rectal toxicity, as well as improved bowel, urinary, and sexual quality of life, with notable improvements in sexual function observed at 37 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data. Karsh, LI., Gross, ET., Pieczonka, CM., et al.[2018]

In a study of 149 patients, hydrogel spacers were effective in significantly reducing rectal radiation dose during prostate cancer treatment, even when the spacers were asymmetrically placed, with 98.7% of patients achieving significant dose reduction.

Rectal wall infiltration of the hydrogel spacer occurred in only 6% of patients, and this infiltration did not correlate with any adverse events or complications, indicating a favorable safety profile for the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: Impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall. Fischer-Valuck, BW., Chundury, A., Gay, H., et al.[2018]

The absorbable hydrogel perirectal spacer (SpaceOAR®) was successfully implanted in 222 men undergoing prostate cancer radiotherapy, with a 99.3% success rate and minimal mild transient side effects, indicating it is a safe and tolerable procedure.

The spacer significantly reduced the rectal radiation dose in 97.3% of patients and led to lower rates of late rectal toxicity and improved bowel quality of life compared to the control group, suggesting it enhances the safety and efficacy of prostate radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrogel Spacer Application Technique, Patient Tolerance and Impact on Prostate Intensity Modulated Radiation Therapy: Results from a Prospective, Multicenter, Pivotal Randomized Controlled Trial. Pieczonka, CM., Mariados, N., Sylvester, JE., et al.[2023]

SpaceOAR® hydrogel injection, approved by the FDA, effectively reduces rectal radiation exposure during prostate radiotherapy, leading to lower rates of rectal toxicity, but remains in early clinical use with emerging safety concerns.

A review of safety reports revealed serious complications associated with SpaceOAR, including acute pulmonary embolism and rectal wall erosion, indicating a need for ongoing monitoring and further research as its use becomes more widespread.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Major Complications and Adverse Events Related to the Injection of the SpaceOAR Hydrogel System Before Radiotherapy for Prostate Cancer: Review of the Manufacturer and User Facility Device Experience Database. Aminsharifi, A., Kotamarti, S., Silver, D., et al.[2020]

A new capillary force-based method for seeding prostate cancer cells into hydrogels significantly improved cell distribution and numbers compared to traditional methods like static and centrifugation seeding.

While the cells proliferated well within the hydrogels, a necrotic zone developed after 7 days due to limited oxygen and nutrient diffusion, which could be mitigated by using dynamic culture methods like orbital shaking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capillary force seeding of sphere-templated hydrogels for tissue-engineered prostate cancer xenografts. Long, TJ., Takeno, M., Sprenger, CC., et al.[2021]

In a study of 222 men undergoing radiation therapy for prostate cancer, the use of the SpaceOAR hydrogel significantly reduced the incidence of rectal toxicity, with grade ≥1 toxicity occurring in 2.0% of the spacer group compared to 9.2% in the control group after 3 years.

Quality of life assessments showed that the spacer group experienced less decline in bowel and urinary quality of life compared to the control group, with significant differences in bowel quality of life meeting the threshold for clinical importance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. Hamstra, DA., Mariados, N., Sylvester, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9734283/

Comprehensive review of hydrogel spacers prior to ... Hydrogel spacers provide a low morbidity method potentially reducing rectal toxicity following radiation therapy in men with prostate cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1879850025000955

Implantable Rectal Spacers in Prostate Cancer Radiation ... This systematic review provides an overview of the available literature regarding the efficacy and safety of implantable rectal spacers (IRSs) in reducing ...

3. e-juo.org e-juo.org/m/journal/view.php?number=611

Initial Experiences With SpaceOAR Hydrogel Insertion for ... Statistical analyses evaluated the impact of age, prostate volume, and operative time on complication rates and procedural efficiency. Results.

4. spaceoar.com spaceoar.com/us/en/about-spaceoar-hydrogel.html

What is SpaceOAR™ Hydrogel | Prostate Cancer Rectal ... *After radiotherapy was complete, control patients experienced a clinically significant decline in bowel, urinary and sexual quality of life eight times more ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2767246

Perirectal Hydrogel Spacer Placement and Clinical ... Perirectal hydrogel spacer placement was associated with less rectal irradiation, fewer rectal toxic effects, and higher bowel-related quality of life in long- ...