Prospective Evaluation of Pencil Beam Scanning Proton Therapy for Previously Irradiated Tumors

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Age 18 years.

- Patient provides study specific informed consent prior to study entry.

- Documented history and physical exam within 90 days prior to registration.

- ECOG PS 0, 1, or 2 within 90 days prior to registration.

Exclusion Criteria:

- Non malignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up.

- Prior invasive non study malignancy unless disease free for ≥ 3 years.

- Non melanoma skin cancer, low risk prostate cancer, well differentiated thyroid cancers, in situ carcinomas of the oral cavity, cervix, and other organs, and tumors that are not thought to impact the life expectancy of the patient are permissible.

- History of active connective tissue disorder (i.e., systemic lupus erythematosus, scleroderma), dermatomyositis, xeroderma pigmentosum

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05313191
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	The New York Proton Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	CNS Cancer, Head and Neck Cancer, GI Cancer, Gynecologic Cancer, Prostate Cancer, Thoracic Cancer, Breast Cancer

Arms & Interventions

Arms

Experimental: Cohort 1: Central Nervous System

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

Experimental: Cohort 2: Head/Neck

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

Experimental: Cohort 3: Breast

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

Experimental: Cohort 4: Thoracic

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

Experimental: Cohort 5: Gastrointestinal

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

Experimental: Cohort 6: Genitourinary

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.

Experimental: Cohort 7: Gynecological

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

No Intervention: Cohort 8: Registry

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

Interventions

Radiation: - Pencil Beam Scanning Proton Therapy

Use of Pencil Beam Scanning Proton Therapy compared with historical outcomes using photon therapy for the reirradiation of recurrent or new primary malignancies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

The New York Proton Center, New York, New York

Status

Recruiting

Address

The New York Proton Center

New York, New York, 10035

Site Contact

Isabelle Choi, MD

[email protected]

646-968-9060