Clinical Trials /

[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake

NCT03872778

Description:

First in Human study to characterize the safety, tolerability, pharmacokinetics (PK), distribution, radiation dosimetry, and anti-tumor activity of [177Lu]-NeoB in patients with advanced solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake
  • Official Title: A Phase I/IIa Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Whole-body Distribution, Radiation Dosimetry and Anti-tumor Activity of [177Lu]-NeoB Administered in Patients With Advanced Solid Tumors Known to Overexpress Gastrin-releasing Peptide Receptor (GRPR)

Clinical Trial IDs

  • ORG STUDY ID: CAAA603A12101
  • SECONDARY ID: 2018-004727-37
  • NCT ID: NCT03872778

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
[177Lu]-NeoBPhase I Cohort I
[68Ga]-NeoBPhase I Cohort I

Purpose

First in Human study to characterize the safety, tolerability, pharmacokinetics (PK), distribution, radiation dosimetry, and anti-tumor activity of [177Lu]-NeoB in patients with advanced solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake.

Trial Arms

NameTypeDescriptionInterventions
Phase I Cohort IExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 50 mCi (1.85 GBq) cycle 1, 60% Estimated Cumulative Dose (ECD) for cycles 2-4, q6w
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase I Cohort IIExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 60% ECD for 3 cycles (q6w)
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase I Cohort IIIExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 80% ECD for 3 cycles (q6w)
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase I Cohort IVExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 100% ECD for 3 cycles (q6w)
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase I Cohort VExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 120% ECD for 3 cycles (q6w)
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase I Cohort VIExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: 100% ECD for 2 cycles (q6w)
  • [177Lu]-NeoB
  • [68Ga]-NeoB
Phase IIaExperimental[68 Ga]-NeoB: 50 micrograms/dose at screening [177Lu]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
  • [177Lu]-NeoB
  • [68Ga]-NeoB

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent prior to participation

          -  Adult patients with advanced solid tumors known to overexpress GRPR

          -  [68Ga]-NeoB tumor lesion uptake on PET/CT or PET/MRI scan at screening visit (>50% of
             lesions detected with conventional imaging are identified as well by [68Ga]-NeoB
             uptake)

          -  At least one measurable lesion per RECIST 1.1/RANO with a [68Ga]-NeoB uptake

          -  Patients for whom no standard therapy is available, tolerated or appropriate

          -  Presence of at least one tumor lesion confirmed with functional or structural imaging
             (PET, SPECT, CT, MRI, bone scan) within 2 months prior to study entry

          -  Patient Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

          -  Life expectancy more than 6 months.

        Exclusion Criteria:

          -  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60
             mL/min or serum creatinine > 1.5 x ULN.

          -  Platelet count of < 75 x 10e9/L

          -  Absolute neutrophil count (ANC) < 1.0 x 10e9/L

          -  Hemoglobin < 9 g/dL

          -  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit
             of normal (ULN) if no demonstrable liver metastases of > 5 x ULN in the presence of
             liver metastases

          -  Total bilirubin > 1.5 ULN, except for patients with documented Gilbert's syndrome who
             are eligible if total bilirubin ≤ x ULN

          -  Serum amylase and/or lipase > 1.5 ULN

          -  Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of their
             excipients

          -  Impaired cardiac function or clinically significant cardiac disease, including any of
             the following:

               -  Clinically significant and/or uncontrolled heart disease such as congestive heart
                  failure requiring treatment (New York Heart Association (NHYA) grade ≥2),
                  uncontrolled arterial hypertension or clinically significant arrhythmia

               -  LVEF < 50% as determined by echocardiogram (ECHO)

               -  QTcF > 470 msec for females and QTcF >450 msec for males on screening
                  electrocardiogram (ECG) or congenital long QT syndrome

               -  Acute myocardial infarction or unstable angina pectoris < 3 months prior to study
                  entry

          -  Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs
             or with fasting plasma glucose > 160 mg/dL (8.9 mmol/L)

          -  Patients with history of or ongoing acute or chronic pancreatitis

          -  Prior administration of a radiopharmaceutical with therapeutic intent within a period
             corresponding to 10 half-lives of the radionuclide used in such radiopharmaceutical

          -  Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow

          -  Patients with a bone scan showing an excessive skeletal radiopharmaceutical uptake
             with absent or faint activity in soft tissues and the genitourinary tract due to
             diffuse bone/bone marrow metastases in bone scan also called a "superscan"

          -  Prior treatment with Radium=223

          -  Patients who have changed the dose of systemic steroid therapy within less than 2
             weeks prior to study entry or patients for whom steroid dose increase is anticipated
             during the study.

          -  Patients who have received prior systemic anti-cancer treatment within the following
             time frames:

               -  Cyclical chemotherapy within a period that is shorter than the cycle length used
                  for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting
                  study treatment

               -  Biologic therapy (e.g. antibodies), continuous or intermittent small molecule
                  therapeutics, or any other investigational agents within a period which is ≤
                  5T1/2 or ≤ 4 weeks (whichever is longer) prior to study entry

          -  History of somatic or psychiatric disease/condition that may interfere with the
             objectives and assessments of the study.

          -  Malignant disease, other than that being treated in this study. Exceptions to this
             exclusion include the following: malignancies that were treated curatively and have
             not recurred within 2 years prior to study treatment; completely resected basal cell
             and squamous cell skin cancers; any malignancy considered to be indolent and that has
             never required therapy; and completely resected carcinoma in situ of any type

          -  pregnant or breast-feeding women

          -  women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, are not allowed to participate in this study UNLESS they are using
             highly effective methods of contraception throughout the study and for 6 months after
             study drug discontinuation. Highly effective contraception methods include:

               -  Total abstinence

               -  Male or female sterilization

               -  Combination of any two of the following (a+b or a+c or b+c)

                    1. Use of oral, injected, or implanted hormonal methods of contraception. In
                       case of use of oral contraception, women should be stable on the same pill
                       for a minimum of 3 months before taking study treatment.

                    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

                    3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
                       cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
                       suppository. Post-menopausal women are allowed to participate in this study.
                       Women are considered post-menopausal and not of child bearing potential if
                       they have had 12 months of natural (spontaneous) amenorrhea with an
                       appropriate clinical profile (e.g. age appropriate, history of vasomotor
                       symptoms) or six months of spontaneous amenorrhea with serum
                       Follicle-Stimulating Hormone (FSH) levels > 40 mIU/mL [for US only: and
                       estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or
                       without hysterectomy) or tubal ligation at least six weeks prior to
                       screening. In the case of oophorectomy alone, only when the reproductive
                       status of the woman has been confirmed by follow-up hormone level assessment
                       is she considered not of child bearing potential. Sexually active males must
                       use a condom during intercourse while taking the drug and for 6 months after
                       stopping treatment and should not father a child in this period. A condom is
                       required to be used also by vasectomized men in order to prevent delivery of
                       the drug via seminal fluid.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: identify maximum tolerated and/or recommended Phase II dose
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Determine Tissue Activity Curves (ACs) [177Lu-NeoB]
Time Frame:18 months
Safety Issue:
Description:ratio of radioactivity in tissue vs blood
Measure:Determine Time Activity Curves
Time Frame:18 months
Safety Issue:
Description:ratio of % activity injected vs time
Measure:Absorbed radiation dose
Time Frame:18 months
Safety Issue:
Description:absorbed radiation dose to critical organs
Measure:Urinary excretion of [177Lu]-NeoB
Time Frame:18 months
Safety Issue:
Description:measure amount of [177Lu]-NeoB excreted in Urine
Measure:Blood Half-life of [177Lu]-NeoB
Time Frame:18 months
Safety Issue:
Description:
Measure:Organ Residence time of [177Lu]-NeoB
Time Frame:18 months
Safety Issue:
Description:
Measure:Objective Response Rate
Time Frame:18 months
Safety Issue:
Description:
Measure:Duration of Response
Time Frame:18 months
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:18 months
Safety Issue:
Description:
Measure:Adverse Events [177Lu-NeoB]
Time Frame:18 months
Safety Issue:
Description:
Measure:Dose modifications
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Advanced Accelerator Applications

Last Updated

August 6, 2020