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

NCT05313191 | Recruiting DMC FDA Device

• 1 other identifier: NYPC ERC# 2019-002
• Study Type: interventional
• Target: 1,800
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Cancer; Gynecologic Cancer; Prostate Cancer; Thoracic Cancer; Breast Cancer; CNS Cancer; GI Cancer

Keywords

Reirradiation; Cancer; Proton Therapy; Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• To determine the cumulative rate of CTCAE v5.0 Grade ≥3 acute and late treatment related adverse events within 1 year of definitive reirradiation completion using proton therapy for recurrent or second primary tumor.

  5 years

Secondary Outcomes (8)

• To determine the 1 year freedom from local failure.

  1 year

• To determine the 1 year freedom from progression free survival.

  1 year

• To determine the 1 year freedom from overall survival.

  1 year

• To determine the acute cumulative rate of CTCAE v5.0 Grade ≥3 treatment related adverse events at 90 days of reirradiation completion.

  90 days

• To determine the late cumulative rate of CTCAE v5.0 Grade ≥3 treatment related adverse events at 2 years of reirradiation completion.

  2 years

Study Arms (8)

Cohort 1: Central Nervous System

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 2: Head/Neck

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 3: Breast

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 4: Thoracic

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 5: Gastrointestinal

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 6: Genitourinary

EXPERIMENTAL

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.

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 7: Gynecological

EXPERIMENTAL

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

Radiation: Pencil Beam Scanning Proton Therapy

Cohort 8: Registry

NO 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

Interventions

Pencil Beam Scanning Proton Therapy RADIATION

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

Cohort 1: Central Nervous System; Cohort 2: Head/Neck; Cohort 3: Breast; Cohort 4: Thoracic; Cohort 5: Gastrointestinal; Cohort 6: Genitourinary; Cohort 7: Gynecological

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The New York Proton Center: lead

Study Sites (1)

The New York Proton Center

New York, New York, 10035, United States

RECRUITING

MeSH Terms

Conditions

Central Nervous System Neoplasms; Head and Neck Neoplasms; Gastrointestinal Neoplasms; Prostatic Neoplasms; Breast Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Ryan Holder, BS

CONTACT

646-968-9055; research@nyproton.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase: Registry, Phase I, Phase II Study Design/Methodology: Cohort-defined, single arm prospective study

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 6, 2022
• Study Start: January 24, 2022
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)