Proton Therapy for Recurrent Cancer

(ReRT Trial)

Overseen By Isabelle Choi, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The New York Proton Center

Disqualifiers: Connective tissue disorders, Non malignant systemic disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

1800 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Proton Therapy for Recurrent Cancer?

Research shows that intensity modulated proton therapy (IMPT) can improve the precision of radiation delivery, sparing healthy tissue while effectively targeting cancer cells. This has been observed in conditions like pancreatic, thoracic, and esophageal cancers, suggesting potential benefits for recurrent cancer as well. ^{1 2 3 4 5}

Is proton therapy generally safe for humans?

Proton therapy, including intensity modulated proton therapy (IMPT), has been used in treating various cancers like pancreatic, head and neck, and anal cancer. It is known for its ability to target tumors more precisely, potentially reducing damage to surrounding healthy tissues and lowering the risk of side effects compared to traditional radiation therapy. Initial studies suggest it is promising and generally safe, but ongoing research is needed to fully understand its safety profile. ^{1 4 5 6 7}

How is proton therapy different from other treatments for recurrent cancer?

Proton therapy, specifically intensity-modulated proton therapy (IMPT), is unique because it can precisely target tumors while minimizing damage to surrounding healthy tissues, unlike traditional radiation therapies. This precision is particularly beneficial for recurrent cancers where sparing normal tissue is crucial. ^{1 2 3 4 8}

What is the purpose of this trial?

The goal of this clinical research trial is to study the use of differing investigational doses and scheduling for Proton Therapy for tumors previously treated with radiation therapy. Generally, when patients are first treated for cancer with radiation therapy, they are treated with traditional photon (or x-ray) radiation therapy, which uses high-energy waves to kill tumor cells. In some cases, the cancer either returns or a new tumor can present in a different part of the body. With the usual radiation treatment, the photon beams travel all the way through the body. As a result, healthy tissues in front of and behind the tumor are exposed to radiation. Physicians who treat these cases where the tumor has returned often use a much lower dose of radiation to prevent patients from experiencing serious and long-term side-effects. This dose is often not strong enough to destroy the cancerous tumor. Alternatively, they may also treat a smaller area than would be indicated for complete tumor eradication, again in an attempt to prevent serious and long-term toxicities, but at the cost of optimally treating the cancer. Proton therapy, however, may offer a chance to safely deliver a more effective dose and volume of radiation as it is more targeted and can spare healthy tissues surrounding the tumor. The reason we are conducting this research study is to look at whether Proton therapy can be a better way to treat reoccurring tumors in patients who have previously received radiation therapy to the same area, compared to treatment approaches used to date.

Eligibility Criteria

This trial is for adults over 18 who've had radiation therapy before and now have recurring tumors. It's open to those with various cancers, including lung, brain, breast, gastrointestinal, and more. Participants need a recent physical exam and an ECOG performance status of 0-2. Those with severe non-cancer diseases or certain cancer histories are excluded.

Inclusion Criteria

Patient provides study specific informed consent prior to study entry

Documented history and physical exam within 90 days prior to registration

I've been mostly active and able to care for myself in the last 3 months.

Exclusion Criteria

I don't have any health conditions that would stop me from participating in the study.

I have been cancer-free from another type of cancer for over 3 years.

I have a history of conditions like lupus, scleroderma, or dermatomyositis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive investigational doses of Proton Therapy for tumors previously treated with radiation therapy

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Proton Therapy

Trial Overview The study tests Proton Therapy as a targeted treatment for tumors that have returned after previous radiation therapy. Unlike traditional photon radiation that affects tissues beyond the tumor, Proton Therapy aims to deliver higher doses directly to the tumor while sparing surrounding healthy tissue.

Participant Groups

Group I: Cohort 7: Gynecological Experimental Treatment 1 Intervention

Group 1: Locally recurrent gynecological cancer within previous field * Single arm, prospective, phase II study design * Patients with history of gyn cancer for which definitive or adjuvant/salvage PORT was given, now with recurrence within 50% IDL recommended for radiotherapy * At least 1 year between RT courses * No persistent grade 3+ toxicity from prior RT * Concurrent chemotherapy excluded * Uncontrolled or widely metastatic disease * Life expectancy \>6 months

Group II: Cohort 6: Genitourinary Experimental Treatment 1 Intervention

Group 1 Locally recurrent prostate cancer w/in prev. radiation field Phase II * Patients w/recurrent prostate adenocarcinoma w/in prev. irradiated field w/indication for repeat course of radiation * Min. 1 year interval b/w RT courses * Prostate gland or recurrent tumor \<100 cc or 6 cm in largest dimension * No persistent grade 2+ toxicity from prior radiation * Negative metastatic workup (bone scan, CT scan or PSMA/axumin scan Group 2 Regional prostate cancer recurrence adjacent to the previous field Phase II * Patients w/recurrent prostate adenocarcinoma beyond prior RT field (outside 50% IDL) but w/in pelvis) * Min.1 year interval b/w RT courses (EBRT or brachy) * No persistent grade 2+ toxicity from prior radiation Group 3 Prostate Reirradiation Registry * Patients w/recurrent prostate adenocarcinoma (prostate gland, postop bed, or pelvi c LN) who require RT to the prostate or pelvis in the setting of prior pelvis RT * No DM * Concurrent chemotherapy excl.

Group III: Cohort 5: Gastrointestinal Experimental Treatment 1 Intervention

Group 1 Esophagus \& GEJ Reirradiation Phase II * Patients w/history of E/GEJ cancer s/p RT, now w/recurrent/new primary nonmetastatic E/GEJ cancer for which salvage RT is recommended * Negative metastatic workup Group 2 Liver Reirradiation Phase II * Patients w/history of HCC, cholangiocarcinoma or liver mets (any histology), s/p prior EBRT, now with in field recurrence/new primary/met, for which definitive reRT is recommended * CTP A or B7 * Excl. prev. Y 90/radioembolization * Allow prior TACE * Overlap w/50% IDL prior RT * Adequate bone marrow function Group 3 Lower GI Reirradiation Phase II * Patients w/history of rectal/anal cancer s/p RT now w/recurrent/new primary nonmetastatic rectal/anal cancer for whom salvage RT is recommended +/ chemotherapy * Negative metastatic workup (PET/CT or CT C/A/P) Group 4 GI Reirradiation Registry •Patients w/histologically document recurrent or new GI malignancy with prior history of RT w/overlap of current RT volume by the 50% IDL

Group IV: Cohort 4: Thoracic Experimental Treatment 1 Intervention

Group 1: Definitive Reirradiation for Locally Advanced Disease * Single arm, prospective, phase II study * Patients with a history of lung cancer s/p definitive RT , now with local recurrence of new primary centrally located and w/I 50% IDL of prior RT field * Definitive reRT concurrent systemic therapy * Adequate pulmonary function defined as an FEV1 of \>35% (with or without bronchodilator) within 90 days prior to registration * Minimum 6 month interval between RT courses * Negative metastatic workup Group 2: Thoracic Registry Study * Registry design * Patients with histologically confirmed thoracic malignancy (NSCLC, SCLC , mesothelioma, thymoma, carcinoid, intrathoracic sarcoma) with prior thoracic RT * Minimum 3 month interval between RT courses * Negative metastatic workup

Group V: Cohort 3: Breast Experimental Treatment 1 Intervention

Group 1 Partial Breast Reirradiation (Phase II) * Patients with a history of breast cancer s/p BCT, now with small (≤3cm), unicentric, ipsilateral breast cancer recurrence receiving repeat BCT * Node negative * Negative margins * No LVI * Lumpectomy cavity:whole breast \<30% * Minimum 1 year interval between RT courses Group 2: Regional LN and Breast/CW ReRT (Phase II) * Patients with a history of breast cancer s/p RT , now with recurrence or new primary with indication for reirradiation to the breast/chest wall and regional LN * Minimum 1 year interval between RT courses * Negative metastatic workup (PET/CT or CT C/A/P + bone scan) * Excludes concurrent chemotherapy Group 3: Breast Reirradiation Registry * Patients with a history of breast cancer s/p RT , now with recurrence or new primary breast cancer with indication for reirradiation * Some overlaps of dose with prior RT course * Negative metastatic workup (PET/CT or CT C/A/P + bone scan) * Excludes concurrent chemotherapy

Group VI: Cohort 2: Head/Neck Experimental Treatment 1 Intervention

Group 1 Full Dose Reirradiation Phase II * Patients w/history of HNC for which RT was delivered definitively, now with recurrence to h/n amenable to full dose reRT * Gross unresected disease or PORT 2/2 RF * Received at least 40 Gy overlapping w/new target region * Min. 6 month interval b/w RT courses * Overlap of prior RT field (50% IDL) * Subgroup analysis: surgery, HPV status, concurrent ST Group 2 Early (\<6months for prior RT) Palliative H/N ReRT Phase I * Patients w/history of HNC for which RT was delivered definitively/adjuvant setting, now with biopsy proven recurrence to h/n with indication for palliative RT * At least 30 Gy prior RT overlapping with new treatment volume * \<6 month interval between RT courses Group 3 Head/Neck ReRT Registry * Patients w/history of HNC for which RT was delivered now with recurrence/secondary primary requiring reRT * Postop or definitive * Prior RT dose at least 30 Gy overlapping w/new treatment volume * Min.6 month interval b/w RT courses

Group VII: Cohort 1: Central Nervous System Experimental Treatment 1 Intervention

Group 1 Definitive Reirradiation Phase II * Patients w/history of intracranial or spinal (extradural, intradural, and/or intramedullary) CNS tumors for which radiation therapy was prev. delivered either to gross disease or in the postoperative setting * Min. 6 month interval b/w RT courses * Overlap of prior RT field (50% IDL) * Subgroup analysis: receipt of surgery for recurrence/second IC tumor; concurrent ST; tumor histology Group 2 CNS Reirradiation Registry * Patients for whom a repeat course of RT to the CNS is indicated for recurrent disease or secondary primary * Postop or intact setting * Min. 6 month interval b/w RT courses * Overlap of prior RT field (50% IDL) * Histologically/clinically documented recurrent CNS tumor (benign or malignant) * Glioblastoma (histologic or molecular including IDH wildtype) * Astrocytoma (molecular IDH1 mutant) * Oligodendroglioma (molecular 1p19q co deleted) * Meningioma * Ependymoma * Chordoma/chondrosarcoma

Group VIII: Cohort 8: Registry Active Control 1 Intervention

* Registry design * Any cancer patient for whom RT is indicated in the setting of prior RT and do not meet eligibility criteria for other cohorts * Overlap of 50% IDL of current treatment volume with prior RT field

Proton Therapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in European Union as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Canada as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Approved in Japan as Proton Therapy for:

• Head and neck cancer
• Pediatric cancers
• Spine tumors
• Breast cancer
• Sarcoma
• Brain tumors
• Prostate cancer

Who Is Running the Clinical Trial?

The New York Proton Center

Lead Sponsor

Trials

3

Recruited

1,900+

Findings from Research

Pencil-beam scanning intensity modulated proton therapy (IMPT) for localized pancreatic cancer showed significant reductions in radiation exposure to surrounding organs at risk, such as the small bowel and liver, compared to volumetric modulated arc therapy (VMAT).

No patients experienced severe (grade ≥3) treatment-related adverse events, and there was no significant change in health-related quality of life scores during treatment, indicating that IMPT is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. Jethwa, KR., Tryggestad, EJ., Whitaker, TJ., et al.[2022]

Intensity modulated proton therapy (IMPT) was successfully used in 34 patients with lung and mediastinal cancers, showing significant improvements in sparing normal tissues compared to both intensity modulated radiation therapy (IMRT) and passive scattering proton therapy (PSPT).

IMPT achieved lower doses to critical organs like the lungs and heart while maintaining higher doses to the tumor, demonstrating effective motion management and robust treatment planning through advanced 4D CT simulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implementation of intensity modulated proton therapy for thoracic malignancies. Chang, JY., Li, H., Zhu, XR., et al.[2022]

Intensity-modulated proton therapy (IMPT) combined with chemotherapy showed a high clinical complete response rate of 84% in 19 patients with esophageal carcinoma, indicating its efficacy in treating this type of cancer.

With a median follow-up of 17 months, patients experienced a median overall survival of 39.2 months, and the treatment was associated with acceptable levels of acute toxicity, primarily esophagitis and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. Prayongrat, A., Xu, C., Li, H., et al.[2022]

Intensity-modulated photon radiotherapy (IMRT) provided better dose conformity to the prostate cancer target compared to three-dimensional conformal proton therapy (3D-CPT), while both methods effectively delivered the prescribed dose to at least 98% of the target volume.

Proton therapy, particularly with optimized configurations, significantly reduced radiation exposure to the bladder and rectum at lower doses, indicating a potential advantage in sparing healthy tissues during prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Trofimov, A., Nguyen, PL., Coen, JJ., et al.[2020]

Intensity modulated proton therapy (IMPT) enhances the precision of proton beam delivery, allowing for better targeting of tumors while minimizing damage to surrounding healthy tissue compared to traditional X-ray therapies.

IMPT utilizes the unique Bragg peak of protons to achieve localized dose modulation, which can potentially improve treatment outcomes, but it also presents technical and clinical challenges that need to be addressed for effective implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy. Kooy, HM., Grassberger, C.[2018]

Proton radiation therapy, particularly intensity-modulated proton therapy (IMPT), offers better dose localization compared to conventional photon radiation therapy, potentially reducing damage to surrounding healthy tissues in patients with head and neck and skull base tumors.

Initial clinical experiences suggest that IMPT may lead to fewer acute and long-term toxicities, and ongoing multi-institutional trials aim to further establish its effectiveness in treating these complex tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation therapy for head and neck cancer. Chan, AW., Liebsch, NJ.[2018]

In a study of 41 anal cancer patients treated with either intensity modulated proton therapy (IMPT) or intensity modulated radiation therapy (IMRT), IMPT resulted in lower doses to pelvic bone marrow and active bone marrow, suggesting a potential for reduced toxicity.

Despite the lower radiation doses to bone marrow with IMPT, there was no significant difference in hematologic toxicity between the two treatment groups, indicating that IMPT may not lead to fewer severe blood-related side effects compared to IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients. Nelson, B., Tadesse, DG., Sudhoff, M., et al.[2023]

Intensity-modulated proton therapy (IMPT) showed significant dosimetric advantages over intensity-modulated radiotherapy (IMRT) in sparing adjacent organs at risk (OAR) in 15 out of 29 OAR for 10 patients with nasopharyngeal carcinoma.

With a median follow-up of 24.5 months, IMPT achieved a 100% locoregional control rate and an 88.9% overall survival rate, suggesting excellent clinical outcomes that warrant further investigation into potential reductions in toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes. Lewis, GD., Holliday, EB., Kocak-Uzel, E., et al.[2022]

References

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

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. [2022]

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

Clinical implementation of intensity modulated proton therapy for thoracic malignancies. [2022]

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

Clinical outcomes of intensity modulated proton therapy and concurrent chemotherapy in esophageal carcinoma: a single institutional experience. [2022]

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

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Intensity modulated proton therapy. [2018]

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

Proton radiation therapy for head and neck cancer. [2018]

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

Hematologic Toxicity Comparison of Intensity Modulated Proton Therapy and Intensity Modulated Radiation Therapy in Anal Cancer Patients. [2023]

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

Intensity-modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes. [2022]