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JOURNAL ONKOLOGIE – STUDIE

Study to Evaluate the Safety and Activity (Including Distribution) of 177Lu-3BP-227 in Subjects With Solid Tumours Expressing Neurotensin Receptor Type 1.

Rekrutierend

NCT-Nummer:
NCT03525392

Studienbeginn:
Mai 2018

Letztes Update:
25.02.2021

Wirkstoff:
177Lu-3BP-227 (also called 177Lu-IPN01087)

Indikation (Clinical Trials):
Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis, Bone Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Ipsen

Collaborator:
-

Studienleiter

Ipsen Medical Director
Study Director
Ipsen

Kontakt

Studienlocations
(3 von 9)

The University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
University Medical Center Groningen
9713 Groningen
NetherlandsRekrutierend» Google-Maps
Universitäts Spital Zürich
8091 Zürich
SwitzerlandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study is being done because new treatment for patients with metastatic or locally

advanced cancers expressing Neurotensin receptor 1 (NTSR1) is being studied. This study will

be the first administration of a radioactive drug called 177Lu-3BP-227 to patients under

controlled conditions of a clinical study. The purpose of this study is to evaluate how safe

this investigational drug is as well to verify how well it is tolerated by patients after

several intravenous administrations. In addition, we will evaluate the effect of the study

drug on tumoral lesions and how it distributes throughout the body and at which rate it is

removed from the body. Since 177Lu-3BP-227 is a radio-labelled drug, it will also be measured

how the emitted radiation is distributed throughout the body (dosimetry).

The study consists of a phase I with a dose escalation part (and potential expansion cohorts)

and a phase II either in selected or over multiple indications in a basket approach. For the

dose escalation part, it is anticipated that approximately 30 subjects will be included, in

up to six escalation steps. In case of the implementation of phase I expansion cohorts, up to

45 additional subjects will be enrolled. For the phase II, approximately 125 subjects (55

Pancreatic ductal adenocarcinoma and 70 Colorectal cancer subjects) are planned to be

enrolled for Basket trial or Optimal Simon's Two Stage design. If additional cohorts of

subjects with Gastric cancer (GC) or Squamous-cell carcinoma of head and neck (SCCHN) in the

phase II are to be studied, approximately 100 additional subjects will be enrolled.

Ein-/Ausschlusskriterien

Inclusion Criteria :

- Signed informed consent form prior to all study procedures

- Aged 18 years or older.

- Histologically or cytologically confirmed unresectable locally advanced or metastatic

disease and has received prior lines of standard-of-care chemotherapy/treatment and

has no further suitable treatment options and documented decision by a

multidisciplinary oncology board including a specialist of the concerned pathology.

- Subjects have (a) pancreatic ductal adenocarcinoma (PDAC), or (b) colorectal cancer

(CRC), or (c) gastric adenocarcinoma (GC), or (d) gastrointestinal stromal tumours

(GIST), or (e) squamous-cell carcinoma of head and neck (SCCHN), or (f) Ewing Sarcoma

(ES)

- Tumour showing: (a) by uptake of 177Lu-3BP-227 (screening formulation) in known

primary or metastatic sites as judged by the investigator to be greater than

background; or (b) uptake of 111In 3BP 227 in known primary or metastatic sites (for

subjects who participated in Study D FR 01087 002) as judged by the investigator to be

greater than background.

- Measurable disease (based on RECIST version1.1).

- Documentation of progressive disease in the 6 months prior to study start (treatment).

- Eastern Cooperative Oncology Group performance status of 0 or 1 (unless if disability

is related to surgery in ES and Agreed with the Sponsor).

- Adequate organ function as evidenced by: (a) Leukocytes ≥3000/μL (b) Absolute

neutrophil count ≥1500/µL (c) Platelets ≥75,000/µL (d) Hb >9 g/dL or >10 g/dL (if

history of cardiac disease) (e) Total serum bilirubin ≤2 times upper normal

institutional limits (ULN) (f) Aspartate aminotransferase/alanine aminotransferase

(ALT) ≤2.5×ULN (or ≤5×ULN, if subject has liver metastases) (g) Estimated glomerular

filtration rate (eGFR) ≥55 mL/min.

- Estimated life expectancy >3 months.

- Female subjects must not be pregnant or lactating at study entry and during the course

of the study and must not become pregnant for at least 6 months following the last

study treatment. Women of childbearing potential must agree to use a highly effective

method of contraception

- For male subjects, must not father children during the study and for at least 6 months

after the last study treatment and in addition must agree to use a condom for this

period to protect his partner from contamination with the IMP. For males with partners

who are of child bearing potential, effective contraception is a combination of male

condom with either cap, diaphragm or sponge with spermicide (double barrier methods),

but these are not considered to be highly effective. A man is considered to be

infertile if he has had bilateral orchidectomy or successful vasectomy. Effective

contraception includes a female partner of childbearing potential if she is using

highly efficacious contraception, but the male subject must agree to use a condom to

protect his partner as described above.

- Must be willing and able to comply with study restrictions and to remain at the clinic

for the required time during the study period and willing to return to the clinic for

the follow-up evaluation, as specified in the protocol.

Exclusion Criteria :

- Prior treatment received (a) Any antitumor treatment since last documented disease

progression (b) Any chemotherapy within 3 weeks or nitrosourea within 6 weeks prior to

first treatment investigational medicinal product (IMP) administration (c) Any

curative radiotherapy within 4 weeks, or palliative radiotherapy within 7 days prior

to first treatment IMP administration (d) Any monoclonal antibodies within 4 weeks or

tyrosine kinases inhibitors within 2 weeks prior to the first treatment IMP

administration, (e) Any other IMP within 2 weeks prior to first treatment IMP

administration, if the previous compound is a mechanism-based molecularly targeted

agent whose half-life (t1/2) is not well-characterized.

- Brain metastases.

- Nephrectomy, renal transplant or concomitant nephrotoxic therapy putting the subject

at high risk of renal toxicity during the study.

- Only non-measurable metastatic bone lesions

- Existing or planned colostomy during study participation.

- Any history of inflammatory bowel disease.

- Any uncontrolled significant medical, psychiatric or surgical condition or laboratory

finding, that would pose a risk to subject safety or interfere with study

participation or interpretation of individual subject results.

- Clinically significant abnormalities on electrocardiogram (ECG) at screening including

corrected QT interval (Fridericia's formula) >450 msec for males or 470 msec for

females at screening.

- Previously received external beam irradiation to a field that includes more than 30%

of the bone marrow or kidney.

- Any unresolved NCI-CTCAE Grade 2 or higher toxicity (except alopecia) from previous

antitumor treatment and/or medical/surgical procedures/interventions.

- Known allergy to IMP or its excipients administered in this study, including imaging

contrast media.

- Positive pregnancy test (female subjects).

- Likely to be uncompliant or uncooperative during the study, in the judgment of the

investigator.

- Unable to understand the nature, scope, and possible consequences of the study, in the

judgment of the investigator.

- Sponsor employees or investigator site personnel directly affiliated with this study,

and their immediate families. Immediate family is defined as a spouse, parent, child

or sibling, whether biological or legally adopted.

Studien-Rationale

Primary outcome:

1. Incidence of dose limiting toxicities (DLTs) and organ exposure to radiation - phase I (Time Frame - From Day 1 (first administration) up to 6 weeks after the second administration):
DLTs are defined for Investigational Medicinal Product (IMP) related AEs according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale version 4.03. Criteria for Adverse Events (NCI-CTCAE) scale version 4.03



Secondary outcome:

1. Maximal uptake (%) of 177Lu-3BP-227 at target lesions and discernible organs - phase I (Time Frame - During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment))

2. Highest absorbed dose to the target lesions (Gy/GBq) of 177Lu-3BP-227 - phase I (Time Frame - During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment))

3. Specific absorbed per organ (Gy/GBq) of 177Lu-3BP-227 - phase I (Time Frame - During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment))

4. Cumulative absorbed organ doses (Gy) of 177Lu-3BP-227 - phase I (Time Frame - During the core study period from Day 1 up to 14 weeks (From Day 1 to Day 5 post infusion for each cycle of treatment))

5. Observed maximal (peak) concentration (Cmax) of 3BP-227 - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

6. Area under the (plasma concentration versus time) curve (AUC) of 3BP-227 - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

7. Half-life (t1/2) of 3BP-227 - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

8. Clearance (CL) of 3BP-227 - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

9. Volume of distribution (Vd) of 3BP-227 - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

10. Cumulative amount of unchanged drug excreted into the urine (Ae) - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

11. Renal clearance of 177Lu-3BP-227 from plasma (CLR), as measured in plasma and urine - phase I (Time Frame - Day 1: before infusion (baseline), at the end of infusion (0), 5, 30 minutes, 1 and 4, 6, 10 and 18 hours after the end of infusion; Day 2: 24 hours after the end of infusion; Day 3: 48 hours after the end of infusion)

12. Objective response rate of 177Lu-3BP-227 - phase I (Time Frame - From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration)):
Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product

13. Disease control rate of 177Lu-3BP-227 - phase I (Time Frame - From Day 1 up to the end of the long-term follow up period of 60 months (whole study period)):
Determined by RECIST version 1.1 in subjects who received Investigational Medicinal Product

14. Progression-free survival (PFS) - phase I (Time Frame - From Day 1 up to the end of the long-term follow up period of 60 months (whole study period)):
Determined from start of study treatment until occurrence of event and/or end of observation period

15. Overall survival (OS) - phase I (Time Frame - From Day 1 up to the end of the long-term follow up period of 60 months (whole study period)):
Determined from start of study treatment until occurrence of event and/or end of observation period

16. Evaluation of metabolic tumour response using Positron emission tomography (PET) Response Criteria In Solid Tumours (version 1.0) or practical PERCIST - phase I (Time Frame - From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration)):
In centers where PET scans are part of clinical practice

17. Changes in serum tumour markers relevant and specific to the underlying tumour disease - phase I (Time Frame - From Day 1 up to 16 weeks (starts at the first administration and ends 6 weeks after the second administration))

Geprüfte Regime

  • 177Lu-3BP-227 (also called 177Lu-IPN01087) (177Lu-IPN01087):
    The cumulative activity of the treatment investigational medicinal product (IMP) formulation will be administered in two intravenous (i.v.) infusions separated by at least 4 weeks (28 days). Up to 6 administrations can be given (2 cycles plus 4 optional additional)

Quelle: ClinicalTrials.gov


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