Freitag, 3. Mai 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE

Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma

Rekrutierend

NCT-Nummer:
NCT05858710

Studienbeginn:
April 2023

Letztes Update:
18.10.2023

Wirkstoff:
DPPG2-TSL-DOX

Indikation (Clinical Trials):
Sarcoma, Hyperthermia

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Thermosome GmbH

Collaborator:
-

Studienleiter

Peter Reichardt, PD Dr.
Principal Investigator
Helios Klinikum Berlin-Buch GmbH

Kontakt

Studienlocations
(2 von 2)

Studien-Informationen

Detailed Description:

Considering that up to 40 percentage of patients with soft tissue sarcoma (STS) will develop

metastatic disease and that for these patients overall survival (OS) ranges between 3.7 to 25

months it becomes clear that new therapeutic approaches for the treatment of advanced STS are

urgently needed. Doxorubicin (DOX) is a cytotoxic compound that belongs to the class of

anthracyclines. DOX has had market authorization since 1960s and is considered the most

active chemotherapeutic drug for the treatment of STS. DPPG2-TSL-DOX is a novel formulation

of DOX encapsulated in DPPG2-containing thermosensitive liposomes (TSL). Regional

hyperthermia (RHT) with a tumor target temperature of ≥41.5 to ≤44 degree of Celsius combined

with anthracycline-based chemotherapy has shown to improve survival in patients with

localized high-risk STS. Treatment with DPPG2-TSL-DOX aims at combining the confirmed

anti-tumor efficacy of anthracyclines in the treatment of locally advanced STS with

RHT-triggered DOX release from circulating liposomes resulting in 10-15-fold higher local DOX

concentrations in the tumor as observed in preclinical studies.

DPPG2-TSL-DOX combined with RHT has been investigated in feline sarcoma at 1 mg/kg dose level

resembling the clinically recommended dose level of standard DOX with considerably improved

efficacy and better tolerability. The proposed study will characterize the safety and

tolerability and, if applicable, the maximum tolerable dose (MTD) of DPPG2-TSL-DOX in

combination with RHT in patients with advanced or metastatic STS who have been pre-treated

with DOX but not assessed as refractory to DOX. An adapted 3+3 MAD study design with sentinel

dosing and a starting dose of 20 mg/m^2 DPPG2-TSL-DOX is applied in this study to identify

dose-limiting toxicities (DLTs) of DPPG2-TSL-DOX in combination with RHT.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Age at the time of consent ≥18 years

- Patient has provided written informed consent prior to any study-specific procedure

- Locally advanced (unresectable) or metastatic soft tissue sarcoma (STS) histologically

diagnosed by local pathology review for which treatment with doxorubicin (DOX)

monotherapy is appropriate, as confirmed by the investigator

- Pretreatment with DOX combination chemotherapy (DOX/ifosfamide, DOX/dacarbazine or

other anthracycline combination therapies) provided at least stable disease was

achieved. For patients who received DOX in an adjuvant setting, local recurrence free

interval of > 6 months is required

- Progressive disease not suitable for surgery after

1. only one further line of chemotherapy (including tyrosine-kinase inhibitor) if

the regional hyperthermia (RHT) field targets the clinically relevant tumor

manifestation/s (e.g., locally advanced or multifocal intraabdominal STS; diffuse

metastatic STS in which RHT of a tumor manifestation [e.g., liver] is considered

relevant although other systemic metastases are present that do not endanger the

patient, as per the judgment of the investigator), or

2. two or more further lines of chemotherapies (including TKI) for patients with

metastatic STS and a tumor manifestation suitable for RHT

- All previous oncological treatments must have been completed ≥3 weeks (21 days) prior

to the first dose of study treatment, ensuring a sufficient washout period

- Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors

(RECIST 1.1) (Eisenhauer et al. 2009)

- Tumor accessible for RHT

- Left ventricular ejection fraction (LVEF) >50% (within 28 days prior to enrolment)

- Adequate hematologic, organ and coagulation function within 14 days prior to enrolment

as assessed by local lab:

1. Absolute neutrophil count (ANC) ≥1.5×10^9/L. Granulocyte-colony stimulating

factor (G-CSF) cannot be administered within 2 weeks (14 days) prior to enrolment

2. Platelet count ≥100×10^9/L

3. Hemoglobin ≥9.0 g/dL. No transfusions are allowed within 2 weeks (14 days) prior

to enrolment

4. Serum creatinine ≤1.5 times upper limit of normal (ULN)

5. Negative dipstick for proteinuria or if proteinuria ≥2+, then additional 24 h

urine collection <1g protein/ 24 h

6. Total bilirubin within ULN (except for patients with Gilbert's syndrome, who must

have a total bilirubin <3 mg/dL)

7. Alanine aminotransferase (ALT)/ Aspartate aminotransferase (AST) ≤3.0×ULN; if the

liver has tumor involvement, AST and ALT ≤5.0×ULN are acceptable

8. An adequate coagulation function as defined by international normalized ratio

(INR) ≤1.5×ULN or prothrombin time ≤1.5×ULN, and partial thromboplastin time

≤1.5×ULN (unless receiving anticoagulant therapy). Patients receiving

phenprocoumon are recommended to switch to low molecular weight heparin and

should have achieved stable coagulation status prior to the first dose of study

treatment

- Tubular excretion rate (TER) by Mercaptoacetyltriglycin-3 (MAG-3)-clearance ≥ TERLoLi

(TERLoLi = 70% TERNorm)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

- If female, must:

1. Be not of child-bearing potential due to surgical sterilization (at least 6 weeks

following surgical bilateral oophorectomy with or without hysterectomy or tubal

ligation) confirmed by medical history or menopause

2. Be a post-menopausal woman, defined as a woman meeting either of the following

criteria:

i. spontaneous amenorrhea for at least 12 months, not induced by a medical condition

such as anorexia nervosa and not taking medications during the amenorrhea that induced

the amenorrhea (for example, oral contraceptives, hormones, gonadotropin-releasing

hormone, antiestrogens, selective estrogen receptor modulators [SERMs], or

chemotherapy) ii. spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating

hormone level >40 mIU/mL

- Women of childbearing potential (WOCBP) and men able to father a child must be ready

and able to use two medically acceptable methods of birth control per ICH M3 (R2) that

result in a low failure rate of less than 1 percentage per year when used consistently

and correctly beginning at screening, during trial participation, and until 6 months

after last dose of study treatment. Also, partner of male participants, who is of

childbearing potential must use a highly effective method of contraception during the

same duration.

- At least 3 months' life expectancy in the investigator's assessment

Exclusion Criteria:

- Progressive disease under previous treatment with anthracyclines

- Patients already enrolled in any clinical study involving an investigational product

or medical device or have participated within the past 30 days in a clinical trial

involving an investigational product or medical device

- History of another primary malignancy, with the exception of:

1. curatively treated non-melanomatous skin cancer

2. curatively treated cervical carcinoma in situ

3. non-metastatic prostate cancer, or

4. other primary non-hematologic malignancies that had been treated with curative

intent, no known active disease, and no treatment administered during the last 3

years prior to enrolment that the investigator agrees will not affect the

interpretation of study results or would be unsuitable for participation in the

study

- Active fungal, bacterial and/or known viral infection including human immunodeficiency

virus or viral (A, B, or C) hepatitis

- Resting heart rate of >100 bpm

- Uncontrolled intercurrent illness including, but not limited to, an ongoing/active

infection - - Have a serious cardiac condition, such as:

1. unstable angina pectoris

2. angioplasty, cardiac stenting, or myocardial infarction within 6 months of

enrolment

3. valvulopathy that is severe, moderate, or deemed clinically significant

4. arrhythmias that are symptomatic or require treatment

- Have a QTcF interval of >450 msec for males and >470 msec for females on screening

electrocardiogram (ECG) utilizing Fridericia's correction

- Psychiatric illness or social situation that would limit compliance with study

requirements.

- Any planned or required major surgery during the course of the study

- Pregnant or breastfeeding female

- Individuals who are institutionalized on a judicial or regulatory order

Studien-Rationale

Primary outcome:

1. Maximum tolerated dose (MTD (Time Frame - End of study (up to 14 months)):
Assessment of the maximum tolerated dose based on the adapted 3+3 method



Secondary outcome:

1. Adverse Events (AEs) (Time Frame - End of study (up to 14 months)):
Number of treatment-emergent AEs according to CTCAE 5.0

2. Serious Adverse Events (SAEs) (Time Frame - End of study (up to 14 months)):
Number of treatment-emergent SAEs according to CTCAE 5.0

3. Laboratory abnormalities (Time Frame - End of study (up to 14 months)):
Number of laboratory abnormalities

4. Electrocardiogram (ECG) abnormalities (Time Frame - End of study (up to 14 months)):
Number of participants with ECG abnormalities

5. Echocardiogram (ECHO) abnormalities (Time Frame - End of study (up to 14 months)):
Number of participants with ECHO abnormalities

6. Renal toxicities (Time Frame - End of study (up to 14 months)):
Number of participants with renal toxicities

7. Area under the plasma concentration versus time curve (AUC) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
AUC of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

8. Peak Plasma Concentration (cmax) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
cmax of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

9. Time of Peak Plasma Concentration (tmax) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
tmax of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

10. Clearance (Cl) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
Cl of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

11. Mean Residence Time (MRT) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
MRT of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

12. Percent Injected Dose (%ID) without RHT (Time Frame - day 2-3 (+/-3) in the study for each participant):
%ID of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

13. Area under the plasma concentration versus time curve (AUC) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
AUC of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

14. Peak Plasma Concentration (cmax) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
cmax of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

15. Time of Peak Plasma Concentration (tmax) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
tmax of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

16. Clearance (Cl) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
Cl of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

17. Mean Residence Time (MRT) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
MRT of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

18. Percent Injected Dose (%ID) with RHT (Time Frame - day 23-24 (+/-3) in the study for each participant):
%ID of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX without RHT (cycle 1; 12 time points)

Geprüfte Regime

  • DPPG2-TSL-DOX (Doxorubicin):
    DPPG2-TSL-DOX is a thermosensitive liposomal formulation of doxorubicin.

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.