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Evaluate the Safety, Tolerability, Biodistribution and Anti Tumour Activity of 177LU-OPS201 With Companion Imaging 68Ga-OPS202 PET/CT in Previously Treated Subjects With Locally Advanced or Metastatic Cancers Expressing Somatostatin Receptor 2 (SSTR2) (SSTR2+)

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ClinicalTrials.gov Identifier: NCT03773133
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Tracking Information
First Submitted Date  ICMJE November 30, 2018
First Posted Date  ICMJE December 12, 2018
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE May 15, 2019
Estimated Primary Completion Date February 16, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2019)
  • Maximum tolerated cumulative activity (MTCA) - phase I [ Time Frame: From Day 1 (first administration of 177Lu-OPS201) up to 6 weeks after the second administration. ]
    Determined as the incidence of Dose Limiting Toxicities (DLTs) and the cumulative organ absorbed doses (Gy) during two cycles of treatment. if the MTCA is not identified during the phase I, primary endpoint will be the Maximum administrable cumulative activity (MACA).
  • Objective response rate (ORR) over the two treatment cycles - phase II [ Time Frame: 6 weeks after each administration of 177Lu-OPS201 during the core study or at the time of occurrence of first clinical signs of disease progression as determined by the investigator up to 90 days ]
    Objective response is defined as the sum of PR and CR measured by CT or MRI using RECIST version 1.1. Tumour response assessments are performed 6 weeks after each administration of 177Lu-OPS201 during the core study or at the time of occurrence of first clinical signs of disease progression as determined by the investigator.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • Maximum administered cumulative activity (MTCA) - phase I [ Time Frame: From Day 1 (first administration of 177Lu-OPS201) up to 6 weeks after the second administration. ]
    Determined as the incidence of Dose Limiting Toxicities (DLTs) and the cumulative organ absorbed doses (Gy) during two cycles of treatment. if the MTCA is not identified during the phase I, primary endpoint will be the Maximum administrable cumulative activity (MACA).
  • Objective response rate (ORR) over the two treatment cycles - phase II [ Time Frame: 6 weeks after each administration of 177Lu-OPS201 during the core study or at the time of occurrence of first clinical signs of disease progression as determined by the investigator up to 90 days ]
    Objective response is defined as the sum of PR and CR measured by CT or MRI using RECIST version 1.1. Tumour response assessments are performed 6 weeks after each administration of 177Lu-OPS201 during the core study or at the time of occurrence of first clinical signs of disease progression as determined by the investigator.
Change History Complete list of historical versions of study NCT03773133 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2019)
  • Maximum observed concentration of 177Lu-OPS201 (Cmax) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Time to maximum observed concentration of 177Lu-OPS201 (tmax) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Maximal uptake (%) of 177Lu-OPS201 - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Area under the curve (AUC) of 177Lu-OPS201 at the target lesions, discernible organs and blood - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Elimination half life (t1/2) of radioactivity concentrations in blood - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Highest absorbed dose to the target lesions (Gy/GBq) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Specific absorbed dose per organ (Gy/GBq) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Total plasma clearance (CL) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Apparent volume of distribution (Vd) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Cumulative amount (of unchanged drug) excreted into the urine (Ae) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Renal clearance - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) up to 4 cycles ]
  • Mean change in tumour volume - phase I [ Time Frame: 46 weeks after each 177Lu-OPS201 administration compared to Screening as assessed by CT or MRI ]
  • Best overall response - phase I [ Time Frame: Up to 24 months from the study start ]
    The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Pharmacodynamics (PD) the smallest measurements recorded since the treatment started)
  • Overall survival (OS) [ Time Frame: At 1-year and 2-years follow-up from the study start ]
  • Quantitative changes in tumour [ Time Frame: From Screening to 6 weeks after second 177Lu-OPS201 administration up to 90 days ]
  • Durable response rate (DRR) - phase II [ Time Frame: From Screening and 6 weeks after each 177Lu-OPS201 administration up to 90 days ]
    DRR: Complete response (CR) or Partial response (PR) lasting ≥6 months
  • Progression free survival (PFS) - phase I [ Time Frame: From start of study treatment until disease progression or death ]
  • Progression free survival (PFS) - phase II [ Time Frame: From start of study treatment until disease progression or death ]
  • Diagnostic sensitivity of 68Ga-OPS202 [ Time Frame: Up to End of core trial cycle ]
    Diagnostic sensitivity of 68Ga-OPS202 imaging using Response evaluation criteria in solid tumours (RECIST), mGa-RECIST by subject-based analysis and organ-based and lesion-based analysis compared to standard-of-truth (SOT) of Contrast enhanced CT (ceCT) (or ceMRI).
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • Maximum observed plasma drug concentration of 177Lu-OPS201 (Cmax) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Time to maximum observed drug concentration of 177Lu-OPS201 (tmax) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Maximal uptake (%) of 177Lu-OPS201 - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Area under the plasma concentration time curve (AUC) of 177Lu-OPS201 at the target lesions, discernible organs and blood - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Elimination half life (t1/2) of radioactivity concentrations in blood - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Highest absorbed dose to the target lesions (Gy/GBq) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Specific absorbed dose per organ (Gy/GBq) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Total plasma clearance (CL) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Apparent volume of distribution (Vd) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Cumulative amount (of unchanged drug) excreted into the urine (Ae) - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Renal clearance - phase I [ Time Frame: Day 1, 2, 3, 4/5, 6 of each cycle (each cycle is 42 days) ]
  • Mean change in tumour volume - phase II [ Time Frame: 46 weeks after each 177Lu-OPS201 administration compared to Screening as assessed by CT or MRI ]
  • Best overall response - phase I [ Time Frame: Up to 24 months from the study start ]
    The best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Pharmacodynamics (PD) the smallest measurements recorded since the treatment started)
  • Overall survival (OS) [ Time Frame: At 1-year and 2-years follow-up from the study start ]
  • Quantitative changes in tumour [ Time Frame: From Screening to 6 weeks after second 177Lu-OPS201 administration up to 90 days ]
  • Durable response rate (DRR) - phase II [ Time Frame: From Screening and 6 weeks after each 177Lu-OPS201 administration up to 90 days ]
    DRR: Complete response (CR) or Partial response (PR) lasting ≥6 months
  • Progression free survival (PFS) - phase II [ Time Frame: From Screening and 6 weeks after each 177Lu-OPS201 administration up to 90 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluate the Safety, Tolerability, Biodistribution and Anti Tumour Activity of 177LU-OPS201 With Companion Imaging 68Ga-OPS202 PET/CT in Previously Treated Subjects With Locally Advanced or Metastatic Cancers Expressing Somatostatin Receptor 2 (SSTR2)
Official Title  ICMJE A Multicentre, Open-Label Phase I/II Study to Evaluate the Safety, Tolerability, Biodistribution and Anti Tumour Activity of 177LU-OPS201 With Companion Imaging 68Ga OPS202 PET/CT in Previously Treated Subjects With Locally Advanced or Metastatic Cancers Expressing Somatostatin Receptor 2 (SSTR2)
Brief Summary This study consists of two phases. The phase I study is designed to investigate the safety and tolerability of Satoreotide tetraxetan following fractionated i.v. administrations in pre-treated subjects with locally advanced or metastatic cancers expressing sstr2 as identified by Satoreotide trizoxetan Positron Emission Tomography (PET/CT) scans. This phase will encompass both radioactivity escalation and peptide mass dose evaluation. Phase II will assess the efficacy of Satoreotide tetraxetan in subjects in selected indications, in a basket design.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Small Cell Lung Cancer and Breast Cancer
Intervention  ICMJE
  • Drug: Satoreotide tetraxetan
    Radioactivity delivered in 2 administrations (cycles): one loading dose followed by a lower maintenance dose, 6 weeks apart until progression or unacceptable toxicity (up to 4 additional cycles could be administered depending on efficacy and tolerability).
    Other Name: 177Lu-OPS201
  • Drug: Satoreotide trizoxetan
    Imaging companion: 1 administration at screening and one administration at End of core Trial cycle.
    Other Name: 68Ga-OPS202
Study Arms  ICMJE Experimental: Treatment
i.v. administrations of up to three radioactivity levels of Satoreotide tetraxetan.
Interventions:
  • Drug: Satoreotide tetraxetan
  • Drug: Satoreotide trizoxetan
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: June 19, 2019)
30
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2018)
172
Estimated Study Completion Date  ICMJE December 13, 2024
Estimated Primary Completion Date February 16, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Consenting adults of Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
  • Histologically confirmed locally advanced or metastatic disease which has progressed during or after, failed to respond to, or for which there is poor tolerability or after a contraindication to available Standard of Care (SoC) treatment options as per the assessment of the investigator; initially, subjects with the disease below may be considered:

    1. Subjects who had Extensive Disease (ED-SCLC) at presentation who have progressed on or after one line standard chemotherapy. If a subject had Limited Disease (LD-SCLC) at presentation and received surgery and/or radiotherapy as first line treatment (with or without chemotherapy) and has localized relapse, further local treatment (such as surgery) should be considered in addition to the chemotherapy options; For subjects with either ED-SCLC or LD-SCLC, if subjects relapse more than 6 months after first-line treatment, re-treatment with their initial regimen is recommended. Subjects may have received prior immunotherapy.
    2. Subjects with Human Epidermal Growth Factor Receptor (HR+)/(HER2-) metastatic BC after a failure of prior SoC-treatments and who have received, if indicated, at least one line of hormonal therapy, Cyclin-dependent kinase (CDK4/6) inhibitor and/or everolimus for advanced or metastatic disease and at least one line of chemotherapy for metastatic disease; subjects with a Breast Cancer (BRCA)-mutated metastatic disease who may have received a Poly adenosine diphosphate ribose polymerase (PARP) inhibitor, if available, are eligible; prior adjuvant hormonal treatment and prior adjuvant chemotherapy are allowed.
  • Documented progressive disease (radiological, based on RECIST v1.1) within 3 months prior to first study drug administration. Screening study-related images should be sent to the Imaging core laboratory (ICL).
  • Adequate organ function determined within 28 days prior to 177Lu-OPS201 administration, defined as follows:

    • Haematological: white blood cells (WBC) ≥3000/μL, with absolute neutrophil count ≥1000/μL, platelet ≥100,000/μL and haemoglobin ≥9 g/dL (without a need for hematopoietic growth factor or transfusion support).
    • Renal: Estimated glomerular filtration rate (eGFR) ≥55 mL/minute/1.73m2
    • Hepatic: total serum bilirubin ≤2×ULN; aspartate aminotransferase/ alanine aminotransferase ≤2.5×ULN (≤5×ULN if a subject has liver metastases)
  • Formalin fixed paraffin embedded tumour sample (archival tumour sample obtained within 1 month prior to concent from the primary or metastatic lesion OR is willing to undergo newly obtained biopsy prior to the first dose of study treatment. Subjects who are unable or do not concent to provide acceptable tissue may not be enrolled unless there has been prior agreement with the sponsor.
  • 68Ga OPS202 uptake in the target tissue (a primary tumour, lymph nodes longest diameter on PET/CT as confirmed by a central reader.
  • Radiologically, ≥50% matching between the lesions detected on 68Ga OPS202-PET/CT and on 18F-fluorodeoxyglucose (18F-FDG)-PET/CT as confirmed by central reader

Exclusion Criteria:

  • Male subjects with BC.
  • Unstable central nervous system metastasis
  • Centrally located lung tumours that show radiogical evidence (CT or MRI) of either:

    • cavitation or necrosis, or
    • focal invasion for major blood vessels.
  • Subjects had received chemotherapy within the previous 4 weeks or had not recovered from adverse events due to chemotherapy. Additional exclusion criteria were previous hemibody external radiotherapy, systemic radiotherapy with radioisotopes within the previous 24 weeks
  • Previous chemotherapy within a cycle interval, curative radiotherapy within 4 weeks or palliative radiotherapy within 7 days prior to Investigational radiopharmaceutical product (IRPP) administration.
  • Prior treatment with any other investigational medicinal product (IMP) within five half-lives of the previous IMP or within 2 weeks, if the previous compound is a mechanism-based molecularly targeted agent whose half-life is not well characterized and toxicities have not resolved from Grade 2 or higher prior to IRPP administration.
  • Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia and Grade 2 platinum-therapy related neuropathy) from previous antitumour treatment and/or medical/surgical procedures/interventions.
  • Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject at high risk of renal toxicity during the study as assessed by the investigator.
  • Any significant medical or surgical condition that would affect safety or the assessment of efficacy or the ability of a person to comply with the protocol.
  • Any condition that precludes the proper performance of PET and/or SPECT scans, CT scans and/or MRI:

    1. subjects who are not able to tolerate the CT contrast agent.
    2. subjects with metal implants or joint prosthesis (depending on the location, if interferes with the PET and/or CT analysis)
    3. or any other objects that might interfere with the PET and/or CT analysis.
    4. subjects unable to raise arms for prolonged imaging purposes.
    5. subjects unable to lie still for the entire imaging time.
    6. subjects weighing greater than 130 kg (287 lb).
  • Pregnant or lactating female. Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 6 months after the last dose of 177Lu-OPS201.
  • Male subject who is unwilling to use acceptable method of effective contraception during treatment and through 6 months after the last dose of 177Lu-OPS201.
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: Ipsen Recruitment Enquiries clinical.trials@ipsen.com
Listed Location Countries  ICMJE Austria,   Belgium,   France,   Germany,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03773133
Other Study ID Numbers  ICMJE D-FR-01072-002
2017-005173-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
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
Plan to Share IPD: Yes
Plan Description: Where patient data can be anonymised, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available.
Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.
Responsible Party Ipsen
Study Sponsor  ICMJE Ipsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ipsen Medical Director Ipsen
PRS Account Ipsen
Verification Date October 2019

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