Hypoxia Imaging for Esophageal Cancer to Guide Personalized Radiation Therapy

Обзор

This is a Phase I trial evaluating the safety of personalized radiation therapy based on levels of hypoxia identified on FMISO-PET and MRI. All patients will receive a baseline FMISO positron emission tomography (PET) and MRI to identify levels of hypoxia. Patients with tumor hypoxia will receive a higher dose of radiation therapy. Subjects who do not have hypoxic tumors will be treated with the standard-of-care radiation regimen. After fraction 10 of radiation therapy, an additional MRI will be performed. If this interim MRI demonstrates little or no response (as defined in Section 6), an optional boost radiation dose can be administered. Trial enrollment will be conducted in two parts. In Part 1, eight patients will be enrolled. After all eight patients have completed the 30 day dose-limiting toxicity (DLT) period, enrollment will be placed on hold and safety will be evaluated. During the interim analysis, one additional patient will be allowed to be enrolled in the trial. If the trial meets stopping rules as described in Section 11.3, the trial will be re-evaluated by the Data and Safety Monitoring Committee (DSMC) and the Principal Investigator. However, if the rate of DLTs remains below the unacceptable toxicity rate, enrollment will open to the enrollment of eight more patients.

Вмешательства

• Лучевая терапия Radiation
  Prior to the start of study therapy, eligible subjects will receive a FMISO-PET scan. If there is uptake visualized on the scan, the tumor will be considered as hypoxic. If there is no uptake seen on the FMISO-PET scan, tumors will be labeled not hypoxic. Subjects with tumors identified by imaging as hypoxic will be treated with a higher dose of radiation therapy. Tumors will be defined as being hypoxic if FMISO accumulation occurs as demonstrated by standardized uptake value (SUV) uptake in the
• Препарат FMISO PET CT
  Prior to the start of study therapy, eligible subjects will receive a FMISO-PET scan. If there is uptake visualized on the scan, the tumor will be considered as hypoxic. If there is no uptake seen on the FMISO-PET scan, tumors will be labeled not hypoxic.

Первичные конечные точки

• rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 30 days of finishing radiation therapy [Срок оценки: 30 days after last study therapy]
• rate of grade ≥ 4 esophageal adverse events attributed to radiation therapy that occur within 84 days of finishing radiation therapy [Срок оценки: 84 days after last study therapy]
• frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment [Срок оценки: 84 days after last study therapy]

Вторичные конечные точки (2)

• Progression-free survival (PFS) [Срок оценки: Time from study therapy initiation to the time documented disease progression (as assessed by RECIST 1.1) or death from any cause for up to 18 months after last dose of study therapy]
• Pathological complete response (pCR) rate [Срок оценки: Long term follow up to occur for up to 18 months after last dose of study therapy.]

Критерии участия

Критерии включения

• Male or female subject aged ≥ 18 years.
• Esophageal cancer patient eligible to undergo either neoadjuvant or definitive chemoradiation therapy (CRT).

Note: Stage IV patients with limited metastatic disease burden may be eligible if CRT is recommended by the multidisciplinary team.

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

• Women < 50 years of age:

• Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
• Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
• Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥ 50 years of age:

• Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
• Had radiation-induced menopause with last menses >1 year ago; or
• Had chemotherapy-induced menopause with last menses >1 year ago; or
• Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
• Recovery to baseline or ≤ Grade 2 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Критерии исключения

• Unable to undergo an MRI for any reason, including:

• Severe claustrophobia not amenable to pre-medication
• Presence of metallic objects or implanted medical devices in the body that are not MRI-compatible (e.g., non-MRI-compatible cardiac pacemaker, deep brain stimulator, neurostimulator, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
• 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 radiation therapy are eligible for this trial.
• The subject has severe, uncontrolled, significant intercurrent or recent illness that would exclude them from being a candidate for chemoradiation therapy.

• Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
• Known HIV infection with a detectable viral load at the time of screening.

• Note: Patients on effective antiretroviral therapy or who will plan on going on antiretroviral therapy at the time of screening are eligible for this trial. HIV testing is not required for eligibility.
• Known prior severe hypersensitivity to gadolinium, FMISO or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Huntsman Cancer Institute — Salt Lake City

Публикации

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• Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW PMID 26254683
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• Tomblyn MB, Goldman BH, Thomas CR Jr, Benedetti JK, Lenz HJ, Mehta V, Beeker T, Gold PJ, Abbruzzese JL, Blanke CD; SWOG GI Committee. Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414). J Thorac Oncol. 2012 May;7(5):906-12. doi: 10.1097/JTO.0b013e31824c7bed. PMID 22481235

Идентификаторы

NCT: NCT04846309 · HCI137650

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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