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

Trial Summary

What is the purpose of this trial?

There are several single institutional series that have reported their experience with salvage radiotherapy options that include EBRT, LDR and HDR brachytherapy. Gastrointestinal (GI) toxicity with salvage radiotherapy range between14-58%, respectively for patients undergoing re-irradiation. There is a concern for an increased risk of fistula development in these patients who receive second course of radiation. Hypofractionation using SABR has been utilized in the re-irradiation setting for prostate cancer with good tumor control and toxicity outcomes. In order to decrease the rectal toxicity, dose to the rectum should be kept as low as possible. Several techniques can be used to achieve this: tighter dosimetric dose painting, better patient or organ immobilization or use of a biodegradable gel. The Investigators ropose a phase I study to assess placement of a hydrogel spacer between the prostate and rectum, in an effort to decrease toxicity and improve patient's bowel quality of life.

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 data supports the idea that Rectal Hydrogel Spacer for Prostate Cancer is an effective treatment?

The available research shows that the Rectal Hydrogel Spacer, known as SpaceOAR, is effective in reducing the side effects of prostate cancer radiation therapy. Studies indicate that it helps create a safe distance between the prostate and the rectum, which reduces the amount of radiation the rectum receives. This leads to fewer problems with the rectum, bladder, and sexual health both in the short term and long term. Compared to not using the spacer, patients experience less discomfort and fewer complications, making it a beneficial addition to prostate cancer treatment. ^{1 2 3 4 5}

What safety data is available for the rectal hydrogel spacer used in prostate cancer treatment?

The rectal hydrogel spacer, known as SpaceOAR, has been evaluated in several studies, including phase 2 and 3 clinical trials. It is FDA-approved and has shown benefits in reducing rectal radiation dose and toxicity during prostate radiotherapy. However, safety reports indicate potential complications such as pain, needle penetration, gel injection into nearby organs, local inflammation, infection, urinary retention, and rectal injury. More severe complications reported include acute pulmonary embolism, severe anaphylaxis, prostatic abscess, sepsis, rectal wall erosion, and rectourethral fistula. These findings suggest a need for further study of the device's safety as its clinical use increases. ^{1 3 6 7 8}

Is the treatment in the trial titled 'Rectal Hydrogel Spacer for Prostate Cancer' a promising treatment?

Yes, the hydrogel spacer is a promising treatment for prostate cancer. It helps reduce the growth of cancer cells and supports nerve healing, which can help prevent side effects like erectile dysfunction and incontinence after surgery. ^{9 10 11 12 13}

Research Team

Amandeep Taggar, MD

Principal Investigator

Sunnybrook

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data. [2018]

2. United States 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. [2023]

3. United States 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. [2018]

4. Australia pubmed.ncbi.nlm.nih.gov

Late toxicities of prostate cancer radiotherapy with and without hydrogel SpaceAOR insertion. [2020]

5. Australia pubmed.ncbi.nlm.nih.gov

Spontaneous remission of rectal ulcer associated with SpaceOAR® hydrogel insertion in radiotherapy for prostate cancer. [2022]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

First experience in the Czech Republic with perirectal hydrogel injection before radiotherapy for prostate cancer. [2021]

7. United States 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. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Prostate carcinoma cell growth-inhibiting hydrogel supports axonal regeneration in vitro. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Hemostatic gelatin sponge is a superior matrix to matrigel for establishment of LNCaP human prostate cancer in nude mice. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Hydrogel-based 3D model of patient-derived prostate xenograft tumors suitable for drug screening. [2021]

12. Netherlands 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. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Capillary force seeding of sphere-templated hydrogels for tissue-engineered prostate cancer xenografts. [2021]