Trial Title:
Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma
NCT ID:
NCT05858710
Condition:
Sarcoma, Soft Tissue
Conditions: Official terms:
Sarcoma
Hyperthermia
Doxorubicin
Conditions: Keywords:
Sarcoma, Soft Tissue
Doxorubicin/ IV + Liposomes
Doxorubicin
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
an adapted 3+3 multiple ascending dose (MAD) design with sentinel dosing
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
DPPG2-TSL-DOX
Description:
DPPG2-TSL-DOX is a thermosensitive liposomal formulation of doxorubicin.
Arm group label:
IV DPPG2-TSL-DOX
Other name:
Doxorubicin
Summary:
This study aims to explore a new therapeutic approach for advanced soft tissue sarcoma
(STS) by investigating the safety, tolerability, and maximum tolerable dose (MTD) of
DPPG2-TSL-DOX combined with regional hyperthermia (RHT) in patients who have been
pre-treated with doxorubicin (DOX).
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Helios Klinikum Berlin-Buch GmbH
Address:
City:
Berlin
Zip:
13125
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Peter Reichardt, PD Dr.
Investigator:
Last name:
Peter Reichardt, Prof. PD Dr.
Email:
Principal Investigator
Investigator:
Last name:
Annette Reichardt, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Ghani Saeed, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Benjamin Unger, Dr.
Email:
Sub-Investigator
Facility:
Name:
Klinikum der Universität München (KUM) Campus Großhadern
Address:
City:
Munich
Zip:
81377
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Dorit Di Gioia, PD Dr.
Investigator:
Last name:
Dorit Di Gioia, PD Dr.
Email:
Principal Investigator
Investigator:
Last name:
Gesa-Elena Schuebbe, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Sinan Enre Gueler, Dr.
Email:
Sub-Investigator
Investigator:
Last name:
Luc Maxime Berclaz, Dr.
Email:
Sub-Investigator
Start date:
April 18, 2023
Completion date:
December 2024
Lead sponsor:
Agency:
Thermosome GmbH
Agency class:
Industry
Source:
Thermosome GmbH
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05858710
https://www.thermosome.com/
