First-in-Human Phase I and II Study to Determine Safety and Efficacy of Proton-Spatially Fractionated Radiotherapy (P-SFRT) in Retroperitoneal Soft Tissue Sarcoma
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.
• 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