Trial Title:
Proton-Spatially Fractionated Radiotherapy and Standard Radiation Therapy for the Treatment of Newly Diagnosed Retroperitoneal Soft Tissue Sarcoma
NCT ID:
NCT06327477
Condition:
Retroperitoneal Sarcoma
Conditions: Official terms:
Sarcoma
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Radiation
Intervention name:
Intensity-Modulated Radiation Therapy
Description:
Undergo IG-IMRT
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
IMRT
Other name:
Intensity modulated radiation therapy (procedure)
Other name:
Intensity Modulated RT
Other name:
Intensity-Modulated Radiotherapy
Other name:
Radiation, Intensity-Modulated Radiotherapy
Intervention type:
Procedure
Intervention name:
Resection
Description:
Undergo surgical resection
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
Surgical Resection
Intervention type:
Radiation
Intervention name:
Spatially-fractionated Radiation Therapy
Description:
Undergo P-SFRT
Arm group label:
Treatment (P-SFRT, IG-IMRT)
Other name:
GRID Therapy
Other name:
SFRT
Summary:
This phase I/II trial studies the side effects and best dose of proton-spatially
fractionated radiotherapy (P-SFRT) and to see how well it works with standard radiation
therapy in treating patients with newly diagnosed retroperitoneal soft tissue sarcoma.
Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer
cells and shrink tumors. Standard spatially fractionated radiotherapy (SFRT) refers to
how the radiation is delivered to the tumor. SFRT means that different parts of the tumor
are receiving different doses of radiation (fractionation) through beams that allow areas
of higher and lower (peaks and valleys) of doses of the radiation. This spatial
fractionation allows an overall high-dose radiation to be given in the peaks and those
areas of the tumor may release cells and substances that may help with killing tumor
cells, reducing tumor symptoms and shrinking tumors. Proton therapy is a type of
radiation therapy that can overcome some of the barriers of standard SFRT. Protons are
tiny radioactive particles that can be controlled in a beam to travel up to the tumor
and, compared to the particles used in standard radiotherapy, proton therapy can deliver
higher doses to the tumor because smaller doses of radiation are delivered to tissues
away from the tumor. This allows radiation therapy dose-escalated (continuously
increasing the dose of radiation) treatment to tumors even though the tumor is near
radiation sensitive organs like the colon. Giving P-SFRT with standard radiation therapy
may work better in treating patients with newly diagnosed retroperitoneal soft tissue
sarcoma.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) for P-SFRT, which will be used as the
recommended phase II dose (RP2D) for P-SFRT prior to standard fractionated radiation
therapy and surgical intervention for retroperitoneal sarcoma (RPS). (Phase I) II. To
determine the efficacy of P-SFRT prior to standard fractionated radiation therapy and
surgical intervention for RPS. (Phase II)
SECONDARY OBJECTIVES:
I. To determine whether P-SFRT is safe when administered prior to standard fractionated
radiation therapy and surgery for RPS. (Phase I) II. To determine progression-free
survival (PFS) in patients with RPS who have been treated with P-SFRT prior to standard
fractionated radiation therapy and surgical intervention. (Phase II) III. To determine
overall survival (OS) in patients with RPS who have been treated with P-SFRT prior to
standard fractionated radiation therapy and surgical intervention. (Phase II) IV. To
determine objective response (OR) in patients with RPS who have been treated with P-SFRT
prior to standard fractionated radiation therapy and surgical intervention. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of P-SFRT followed by a phase II study.
Patients undergo P-SFRT over 1 fraction and then undergo image-guided intensity modulated
radiation therapy (IG-IMRT) over 25-28 fractions for 35 to 42 days. Patients undergo
surgical resection 21 to 35 days after radiation therapy. Patients undergo blood sample
collection during screening and on study. Patients also undergo biopsy during screening
and computed tomography (CT) on study and on follow up.
After completion of study treatment, patients are followed up at 30 and 90 days after
surgery, and then up to 36 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have newly diagnosed, histologically or cytologically confirmed,
untreated retroperitoneal soft tissue sarcoma
- The soft-tissue sarcoma tumor must be at least 3 cm in diameter
- Patients must have measurable disease according to Response Evaluation Criteria in
Solid Tumors (RECIST) version (v) 1.1.
- Patients must be age ≥ 18 years on day of signing any informed consent documents
- Patients must exhibit a performance status of 0 or 1 on the Eastern Cooperative
Oncology Group (ECOG) performance scale or >70% on the Karnofsky Scale
- Leukocytes (white blood cells [WBC]) ≥ 3,000/mcL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Note: growth factor/transfusion is not permitted prior to these measurements
being taken
- Hemoglobin (Hgb) ≥ 9 g/d
- Platelets (PLT) ≥ 100,000/mcL
- Total bilirubin < 1.5 x upper limit of normal (ULN) (or direct bilirubin < ULN)
- Aspartate Transferase (AST) ( serum glutamic-oxaloacetic transaminase [SGOT]) ≤ 2.5
x institutional ULN
- Alanine transaminase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 2.5 x
institutional ULN
- Creatinine ≤ 1.5 x upper limit of normal (ULN)
- Creatinine clearance ≥ 50mL/min
- International normalized ratio (INR) (or prothrombin time [PT] or partial
thromboplastin time [PTT]; one will be used) < 1.5 x ULN (unless subject is
receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT)
is within therapeutic range of intended use of anticoagulants [within 10 days of
treatment initiation])
- Activated partial thromboplastin time (aPTT) < 1.5 X ULN (unless subject is
receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of
intended use of anticoagulants [within 10 days of treatment initiation])
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Patients of child-bearing potential (POCBP) must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) from time of informed
consent and for the duration of study participation. Patients who can impregnate
their partners must agree to use adequate contraception (hormonal or barrier method
of birth control, abstinence) from time of informed consent and for the duration of
study participation. Should a patient become pregnant or suspect they are pregnant
while they or their partner is participating in this study, they should inform their
treating physician immediately.
- Note: At the discretion of the investigator, acceptable methods of
contraception may include total abstinence in cases where the lifestyle of the
patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation,
symptothermal, postovulation methods] and withdrawal are not acceptable methods
of contraception.)
- Note: A POCBP is any person with an egg-producing reproductive tract
(regardless of sexual orientation, having undergone a tubal ligation, or
remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy
- Has had menses at any time in the preceding 12 consecutive months (and
therefore has not been naturally postmenopausal for > 12 months)
- POCBP must have a negative urine pregnancy test within 72 hours prior to undergoing
CT simulation for P-SFRT. If a urine pregnancy test is positive or cannot be
confirmed negative, a serum pregnancy test will be required
- POCBP must be willing and able to use an adequate method of contraception
- Patients with sperm-producing reproductive capacity (PWSPRC) must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
from time of informed consent, for the duration of study participation, and for 120
days following completion of therapy. PWSPRC treated or enrolled on this protocol
must also agree to refrain from donating sperm from time of informed consent for the
duration of study participation and for 120 days following completion of therapy
- Patients must have the ability to understand and the willingness to sign a written
informed consent document
- Patients must be medically fit to undergo surgery
- Patients must have plans to undergo neoadjuvant radiation therapy and surgery with
curative intent
Exclusion Criteria:
- Patients who have had one of the following soft tissue sarcoma subtypes where
neoadjuvant chemotherapy is established as standard-of-care:
- Extra-skeletal Ewing sarcoma
- Embryonal rhabdomyosarcoma
- Alveolar rhabdomyosarcoma
- Desmoplastic small round cell tumor
- Patients who have had any prior radiation therapy to the affected area
- Patients who have had chemotherapy, radiotherapy, or other antineoplastic agents ≤
28 days (6 weeks for nitrosureas or mitomycin C) prior to planned treatment start
date
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia
- Patients who have taken steroid therapy or any other immunosuppressive therapy
within 7 days of first dose prior to trial treatment
- Patients with a known history of active tuberculosis (TB) (Bacillus tuberculosis)
- Patients with a known history of active hepatitis B (e.g., hepatitis B surface
antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic
acid [RNA] [qualitative] is detected) infection
- Patients with current or a history of any distant metastatic disease (including
brain). Note: an isolated or oligo-metastatic regional occurrence may be allowed if
all other criteria have been met and curative attempt is being pursued
- Patients with a known history of (non-infectious) pneumonitis that required steroids
or had evidence of current pneumonitis
- Patients who have received a live vaccine within 30 days of planned start of study
therapy. Note: Seasonal influenza vaccines for injection are generally killed virus
vaccines, and as such, patients who have received these vaccines are not excluded;
however, intranasal influenza vaccines are live attenuated vaccines and are not
allowed
- Patients who have had an allogenic tissue/solid organ transplant
- Patients with a history of inflammatory bowel disorders (i.e., ulcerative colitis,
Crohn's disease) or rheumatologic disorders (i.e., Sjogren's, scleroderma,
rheumatoid arthritis) that serve as a contraindication to retroperitoneal radiation
therapy
- Patients who have an uncontrolled intercurrent illness including, but not limited to
any of the following, are not eligible:
- Hypertension that is not controlled on medication
- Ongoing or active infection requiring systemic treatment
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Major surgery within 30 days of registration
- Any other illness or condition that the treating investigator feels would
interfere with study compliance or would compromise the patient¡¦s safety or
study endpoints
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements
- Patients who are pregnant (positive urine pregnancy test within 72 hours prior to
enrollment) or nursing. If a urine pregnancy test is positive or cannot be confirmed
negative, a serum pregnancy test will be required
- Patients who are expecting to become pregnant or impregnate their partner within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment
- Patients who are currently participating in or have participated in a study of an
investigational agent or has used an investigational device within 4 weeks prior to
the first dose of study intervention
- Other study specific or disease criteria for exclusion (e.g., certain disease
sub-types that are not eligible, patients who are unable to swallow oral medication
if the study involves oral agents, etc.)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Seth M. Pollack
Phone:
312-695-6180
Investigator:
Last name:
Seth M. Pollack, MD
Email:
Principal Investigator
Start date:
April 2, 2024
Completion date:
July 1, 2028
Lead sponsor:
Agency:
Northwestern University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Northwestern University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06327477
