First-in-human Study of the Theranostic Pair [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G in Pancreatic Cancer

Обзор

This is a Phase I, first-in-human study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G theranostic pair in patients with locally advanced or metastatic pancreatic adenocarcinoma (PDAC).

Подробное описание

This is a Phase I, first-in-human study to evaluate the safety and efficacy of the \[68Ga\]Ga DOTA-5G /\[177Lu\]Lu DOTA-ABM-5G theranostic pair in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). PET imaging using \[68Ga\]Ga DOTA-5G will be used to diagnose patients who are eligible for the \[177Lu\]Lu DOTA-ABM-5G. The overall purpose of this study is to identify the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) of \[177Lu\]Lu DOTA-ABM-5G. A 3+3 study design in is proposed to identify the RP2D of \[177Lu\]Lu DOTA-ABM-5G. An expansion group will receive the RP2D in order to obtain initial estimates of response and additional information on safety of \[177Lu\]Lu DOTA-ABM-5G.

The hypotheses of this phase I study are that a) \[68Ga\]Ga DOTA-5G will detect lesions in patients with locally advanced or metastatic pancreas cancer b) the theranostic pair \[68Ga\]Ga DOTA-5G/ \[177Lu\]Lu DOTA-ABM-5G will be safe and well tolerated c) we will be able to identify a Recommended Phase 2 Dose (RP2D) for \[177Lu\]Lu DOTA-ABM-5G therapy to be used in subsequent Phase II trials.

Вмешательства

• Препарат [68Ga]Ga DOTA-5G and [177Lu]Lu DOTA-ABM-5G.
  PET imaging using \[68Ga\]Ga DOTA-5G will be used to diagnose patients who are eligible for treatment with the \[177Lu\]Lu DOTA-ABM-5G.

Первичные конечные точки

• [68Ga]Ga DOTA-5G PET/CT imaging [Срок оценки: 2 hours from time of injection]
• [177Lu]Lu DOTA-ABM-5G dose escalation therapy [Срок оценки: 30 days from time of injection]

Вторичные конечные точки (1)

• Assessment of organ dosimetry of [177Lu]Lu DOTA-ABM-5G [Срок оценки: 7-14 days from time of injection]

Критерии участия

Критерии включения

\[68Ga\]Ga DOTA-5G PET/CT Inclusion Criteria:

• Ability to understand and willingness to sign a written informed consent document.
• Age 18 or more years
• Confirmed presence of locally advanced, unresectable or metastatic pancreatic adenocarcinoma (other pancreatic malignant histologies are excluded) with measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion > 1 cm or lymph node > 1.5 cm in short axis)
• Participant must have documented tumor progression during or following at least one prior systemic regimen as established by CT or MRI scan within 28 days of enrollment
• Eastern Cooperative Oncology Group Performance Status ≤ 2
• Participant must have completed prior chemotherapy at least 2 weeks (washout period) prior to \[68Ga\]Ga DOTA-5G PET scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved to Grade 1 or baseline.
• Hematologic parameters defined as:

• Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 8 g/dL
• Blood chemistry levels defined as:

• AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
• Total bilirubin ≤ 2 times ULN
• Creatinine ≤ 2 times ULN
• Anticipated life expectancy ≥ 3 months
• Able to remain motionless for up to 30-60 minutes per scan

\[177Lu\]Lu DOTA-ABM-5G therapy Inclusion Criteria:

• Completion of entry into \[68Ga\]Ga DOTA-5G PET study and completion of scan
• The presence of at least one measurable disease by \[68Ga\]Ga DOTA-5G PET/CT (SUVmax>2-fold above normal lung or liver)

Критерии исключения

• \[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G therapy Exclusion Criteria:

• Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA)
• Participants with Class 3 or 4 NYHA Congestive Heart Failure
• Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding)
• Pregnant or lactating women
• Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e. larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks
• Has an additional active malignancy requiring therapy within the past 2 years
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Psychiatric illness/social situations that would interfere with compliance with study requirements
• Previous radiation therapy for the treatment of advanced or metastatic disease
• Cannot undergo PET/CT scanning because of weight limits (350 lbs)
• INR>1.2; PTT>5 seconds above UNL

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of California Davis — Sacramento

Идентификаторы

NCT: NCT04665947 · 1667622

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗