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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03872778
Recruitment Status : Recruiting
First Posted : March 13, 2019
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Advanced Accelerator Applications

Tracking Information
First Submitted Date  ICMJE March 11, 2019
First Posted Date  ICMJE March 13, 2019
Last Update Posted Date July 24, 2019
Actual Study Start Date  ICMJE May 24, 2019
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • Phase I: identify maximum tolerated and/or recommended Phase II dose [ Time Frame: 18 months ]
  • Phase II: assess disease control rate 20 weeks after completion of treatment [ Time Frame: 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03872778 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • Determine Tissue Activity Curves (ACs) [177Lu-NeoB] [ Time Frame: 18 months ]
    ratio of radioactivity in tissue vs blood
  • Determine Time Activity Curves [ Time Frame: 18 months ]
    ratio of % activity injected vs time
  • Absorbed radiation dose [ Time Frame: 18 months ]
    absorbed radiation dose to critical organs
  • Urinary excretion of [177Lu]-NeoB [ Time Frame: 18 months ]
    measure amount of [177Lu]-NeoB excreted in Urine
  • Blood Half-life of [177Lu]-NeoB [ Time Frame: 18 months ]
  • Organ Residence time of [177Lu]-NeoB [ Time Frame: 18 months ]
  • Objective Response Rate [ Time Frame: 18 months ]
  • Duration of Response [ Time Frame: 18 months ]
  • Progression Free Survival [ Time Frame: 18 months ]
  • Adverse Events [177Lu-NeoB] [ Time Frame: 18 months ]
  • Dose modifications [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 11, 2019)
  • Relative radiotracer uptake [ Time Frame: 18 months ]
  • Adverse Events [68Ga-NeoB] [ Time Frame: 18 months ]
  • [177Lu]-NeoB vs [68Ga]-NeoB biodistribution [ Time Frame: 18 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake
Official Title  ICMJE A Phase I/IIa Open-label, Multi-center Study to Evaluate the Safety, Tolerabiity, 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Phase I: dose range finding to identify Recommended Phase II Dose Phase IIa: assessment of anti-tumor activity
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: [177Lu]-NeoB
    [177Lu]-NeoB: peptide receptor radionuclide therapy
  • Drug: [68Ga]-NeoB
    [68Ga]-NeoB radioactive diagnostic agent
Study Arms  ICMJE
  • Experimental: Phase I Cohort I

    [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

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase I Cohort II

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: 60% ECD for 3 cycles (q6w)

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase I Cohort III

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: 80% ECD for 3 cycles (q6w)

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase I Cohort IV

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: 100% ECD for 3 cycles (q6w)

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase I Cohort V

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: 120% ECD for 3 cycles (q6w)

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase I Cohort VI

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: 100% ECD for 3 cycles (q6w)

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
  • Experimental: Phase IIa

    [68 Ga]-NeoB: 50 micrograms/dose at screening

    [177Lu]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w

    Interventions:
    • Drug: [177Lu]-NeoB
    • Drug: [68Ga]-NeoB
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 11, 2019)
71
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Frederic Cortes, Ph.D. +41 78 732 28 45 frederic.cortes@adacap.com
Listed Location Countries  ICMJE Austria,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03872778
Other Study ID Numbers  ICMJE CAAA603A12101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Advanced Accelerator Applications
Study Sponsor  ICMJE Advanced Accelerator Applications
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Advanced Accelerator Applications
PRS Account Advanced Accelerator Applications
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP