Clinical trial NCT04849247: 68Ga-DOTA-FAPI and 177Lu-DOTA-FAPI Theranostic Pair in Patients With Various Types of Cancer (Locally Advanced or Metastatic Cancer)
Official title: 68Ga-DOTA-FAPI and 177Lu-DOTA-FAPI Theranostic Pair in Patients With Various Types of Cancer (Locally Advanced or Metastatic Cancer)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: 177Lu-DOTA-FAPI
68Ga-DOTA-FAPI
Theranostic
Lead sponsor: The First Affiliated Hospital of Xiamen University
Sponsor class: OTHER
First posted: 2021-04-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a first-in-human 3 + 3 study design to identify dose limiting toxicity and recommended phase 2 dose Masking: None (Open Label)
Primary purpose: TREATMENT

Brief summary: This is a Phase I, first-in-human study to evaluate the safety and efficacy of the 68Ga-DOTA-FAPI and 177Lu-DOTA-FAPI theranostic pair in patients with various types of cancer (locally advanced or metastatic cancer).

Detailed description: This is a Phase I, first-in-human study to evaluate the safety and efficacy of the 68Ga-DOTA-FAPI and 177Lu-DOTA-FAPI theranostic pair in patients with various types of cancer. PET imaging using 68Ga-DOTA-FAPI will be used to diagnose patients who are eligible for the 177Lu-DOTA-FAPI. The overall purpose of this study is to identify the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) of 177Lu-DOTA-FAPI. A 3+3 study design in is proposed to identify the RP2D of 177Lu-DOTA-FAPI. An expansion group will receive the RP2D in order to obtain initial estimates of response and additional information on safety of 177Lu-DOTA-FAPI.

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

Eligibility criteria: Inclusion Criteria:

* \[68Ga\]Ga-DOTA-FAPI PET/CT Inclusion Criteria: (i) adult participants (aged 18 years or order); (ii) Confirmed presence of various types of locally advanced or metastatic cancer 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); (iii) 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; (iv) participants who were able to provide informed consent (signed by participant, parent or legal representative) and assent according to the guidelines of the Clinical Research Ethics Committee. (v) Eastern Cooperative Oncology Group Performance Status ≤ 2; (vi) Participant must have completed prior therapy at least 1 month (washout period) prior to \[68Ga\]Ga DOTA-FAPI 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:

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

  (i) AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN); (ii) Total bilirubin ≤ 2 times ULN; (iii) Creatinine ≤ 2 times ULN; (iv) Anticipated life expectancy ≥ 6 months; (v) Able to remain motionless for up to 10-20 minutes per scan;
* \[177Lu\]Lu-DOTA-FAPI therapy Inclusion Criteria: (i) Completion of entry into \[68Ga\]Ga-DOTA-FAPI PET study and completion of scan; (ii) CThe presence of at least one measurable disease by \[68Ga\]Ga-DOTA-FAPI PET/CT (SUVmax \> 10-fold above normal lung or liver);
* Exclusion Criteria:

  (i) 1.Participant on any chemical anticoagulant including antiplatelet agents (excluding ASA); (ii)Participants with Class 3 or 4 NYHA Congestive Heart Failure (iii) Clinically significant bleeding within two weeks prior to trial entry (e.g. gastrointestinal bleeding, intracranial bleeding); (iv) Pregnant or lactating women; (v)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; (vi)Has an additional active malignancy requiring therapy within the past 2 years; (vii)Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy; (viii)Psychiatric illness/social situations that would interfere with compliance with study requirements; (ix)Cannot undergo PET/CT scanning because of weight limits (350 lbs); (x)INR\>1.2; PTT\>5 seconds above UNL

Primary outcomes:
measure: 68Ga-DOTA-FAPI PET/CT imaging
timeFrame: 1 hours from time of injection
measure: [177Lu]Lu-DOTA-FAPI dose escalation therapy
timeFrame: 60 days from time of injection
Secondary outcomes:
measure: Assessment of organ dosimetry of 177Lu-DOTA-FAPI
timeFrame: 1-7 days from time of injection
Other outcomes:
Locations:
city: XiaMen
country: China
facility: First affiliated hospital of xiamen university
state: Fujian
Study officials:
affiliation: The First Affiliated Hospital of Xiamen University
name: Long Sun, PhD
role: STUDY_CHAIR
References: