Trial Title:
Promitil Treatment of Patients With Solid Tumors Associated With Deleterious Mutations Who Have Progressed After Therapy
NCT ID:
NCT06478862
Condition:
Cancer of Ovary
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Ovarian Neoplasms
Mitomycins
Mitomycin
Conditions: Keywords:
Solid tumors
metastatic
inoperable
BRCA mutations
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
There will be 2 cohorts with up to 10 patients per cohort indication
(ovarian/pancreatic). Eligible patients will be assigned in parallel to receive 6 cycles
of Promitil treatment.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Promitil
Description:
The 10 patients recruited in each of the cohorts will receive intravenously (IV)
administered 2.0 mg/kg Promitil on Day 1 of each 28-day cycle, for up to 6 cycles.
Subjects who complete the 6-cycle Treatment Phase have the option to continue to receive
Promitil until disease progression, death, unacceptable toxicity or withdrawal of
consent.
Arm group label:
Ovarian cancer
Arm group label:
Pancreatic cancer
Other name:
Pegylated Liposomal Mitomycin-C Lipid-based Prodrug
Summary:
This multicenter Phase 2a study was designed to evaluate the safety, tolerability, and
efficacy of Promitil in patients with recurrent ovarian cancer and inoperable, locally
advanced or metastatic pancreatic cancer, which bears deleterious germline or somatic
mutations in BRCA1, BRCA2, or HRD (homologous recombination deficiency) -related genes.
Based on reported preclinical and clinical efficacy of Mitomycin C in BRCA-mutated
tumors, and together with the demonstrated improved safety profile of Promitil in humans,
it is expected that this liposomal formulation will have a favorable therapeutic index
and significant clinical antitumor activity in patients with tumors bearing BRCA 1/2
and/or PALB2 mutations.
Detailed description:
The study will include a Screening, Treatment Phase and Long-Term Follow-up (LTFU) Phase.
Upon signing the informed consent form, all subjects will undergo screening procedures to
assess eligibility within 21 days prior to receiving study drug. Eligible subjects will
be intravenously (IV) administered 2.0 mg/kg Promitil on Day 1 of each 28-day cycle, for
up to 6 cycles. Subjects who complete the 6-cycle Treatment Phase have the option to
continue to receive Promitil until disease progression, death, unacceptable toxicity or
withdrawal of consent. During the 6-month Treatment Phase, safety assessments will be
conducted at each study visit (Days 1, 2, 7 and 14 of Cycle 1, Day 1 of Cycle 2 and
Cycles 4 and beyond and Days 1, 2 and 7 of Cycle 3). Safety will be assessed by
measurement of weight, physical examinations, vital signs, ECG recordings, blood
chemistry, hematologic and urinalysis parameters, and review of Adverse and Serious
Adverse events (SAEs) and concomitant medications. Response will be assessed by
CT/MRI/PET-CT scans and biomarker levels, with imaging conducted every 8 weeks (every 2
treatment cycles).For patients who stopped receiving Promitil for any reason other than
disease progression, response will continue to be assessed every 12 weeks, until disease
progression, death or withdrawal of consent, but no later than 1 year from first dose of
Promitil. Once study treatment ends, all subjects will be followed up long-term, with
survival status assessed every 3 months for up to 1 year or until death, the earlier of
the two.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 18 years of age or older on day of consent
2. Patient with either one of the following histologically or cytologically confirmed,
deemed incurable malignancies:
1. Recurrent ovarian cancer
2. Inoperable, locally advanced or metastatic pancreatic ductal adenocarcinoma
(PDAC)
3. Patient with PDAC measurable by RECIST 1.1. Previously irradiated lesions may be
considered measurable if there has been demonstrated progression in these lesions.
Ovarian cancer patients can have either measurable or non-measurable lesions (i.e.,
ovarian cancer patients with mostly ascites or pleural effusion are eligible)
4. Tumor with a known pathogenic or likely pathogenic germline or somatic mutation in
BRCA1, BRCA2 or HRD-related genes as determined by a Clinical Laboratory Improvement
Amendments (CLIA)-certified or equivalently accredited laboratory. Note: Patients
with positive HRD score can be eligible regardless of any evidence for germline or
somatic mutations
5. Patient received at least 1 line of chemotherapy for advanced pancreatic
adenocarcinoma or ovarian cancer. Prior neoadjuvant and adjuvant chemotherapy are
allowed, and platinum re-challenge is allowed for ovarian cancer patients for whom
it is felt to be in their best interests, as determined by the Investigator. Prior
PARP inhibitor, hormonal, biological, or immunological therapy are allowed.
Palliative radiation therapy is allowed, provided it was/will be completed ≥2 weeks
prior starting trial therapy
6. Capable of providing written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form
7. ECOG performance status of 0 or 1
8. Adequate organ function as defined by:
1. Absolute neutrophil count (ANC) ≥ 1500/µL
2. Platelet count ≥ 100,000/µL
3. Hemoglobin ≥ 9 g/dL
4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
5. AST and ALT ≤ 3 x ULN OR ≤ 5 x ULN in the presence of liver metastases
6. Albumin ≥ 3g/dL
7. INR<1.5 unless on anticoagulants
9. Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/minute (as calculated by the
Cockcroft-Gault formula)
10. Estimated life expectancy of at least 3 months
11. Patients (men and women) of reproductive potential willing and able to use an
acceptable method of birth control as approved by the PI
12. With the exception of alopecia and neuropathy, resolution of all acute toxic effects
of any prior chemotherapy, surgery or radiotherapy to NCI CTCAE (Version 5.0) Grade
≤ 1 or to the baseline laboratory values as defined in Inclusion Criteria Number 8
and 9.
Exclusion Criteria:
1. Uncontrolled intercurrent illness including, but not limited to, severe or ongoing
active infection, symptomatic congestive heart failure, unstable angina pectoris,
serious cardiac arrhythmias, or psychiatric illness/social situations that would
limit compliance with study requirements
2. Any other severe concurrent disease which, in the judgment of the investigator,
would make the subject unsuited for treatment
3. History of chronic active hepatitis, including carriage of hepatitis B virus (HBV)
or hepatitis C virus (HCV), unless patient is adequately treated and shown to be
serum virus-free
4. Evidence of active bleeding
5. Untreated brain metastases Note: Patients with brain metastases treated by surgery
or radiation who are stable and symptom-free (≤ 4 mg dexamethasone/day) are eligible
to participate in the study
6. Patient is pregnant or lactating
7. Prior intravenous treatment with MMC, either alone or in combination
8. Other anti-cancer treatment within 2 weeks before start of study drug
9. Other myelosuppressive treatment within 4 weeks before start of study drug
10. Treatment with other investigational drugs within 5 drug half-lives of day 1 of
study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Soroka Medical Center
Address:
City:
Be'er Sheva
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Claudia Rahimian
Phone:
+972-8-6245198
Email:
ClaudiaRa@clalit.org.il
Investigator:
Last name:
Amichai Meirovitz
Email:
Principal Investigator
Facility:
Name:
Rambam Health Care Campus
Address:
City:
Haifa
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Ruth Perets, Dr.
Email:
ru_perets@rambam.health.gov.il
Contact backup:
Last name:
Inbar Kolsky
Phone:
+972-4-7776223
Email:
I_KOLSKY@rambam.health.gov.il
Investigator:
Last name:
Ruth Perets, Dr.
Email:
Principal Investigator
Facility:
Name:
Wolfson Medica Center
Address:
City:
H̱olon
Zip:
5822012
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Gali Bortnik
Phone:
+972-3-5028408
Email:
scurology@wmc.gov.il
Investigator:
Last name:
Tali Levy, MD
Email:
Principal Investigator
Facility:
Name:
Shaare Zedek Medical Center
Address:
City:
Jerusalem
Zip:
9103102
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Dalia Sherizen
Phone:
+972-2-6555424
Email:
daliash@szmc.org.il
Contact backup:
Last name:
Aaron Goldberg
Phone:
+972-2-5645637
Email:
aarongo@szmc.org.il
Investigator:
Last name:
Ofer Purim, MD
Email:
Principal Investigator
Investigator:
Last name:
Ora Rosengarten, MD
Email:
Principal Investigator
Facility:
Name:
Tel-Aviv Sourasky Medical Center
Address:
City:
Tel-Aviv
Zip:
64239
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Ravit Geva, Dr.
Phone:
972-3-6973082
Email:
ravitg@tlvmc.gov.il
Contact backup:
Last name:
Yasmine Levi
Phone:
+972-3-6972484
Email:
yasminlevi@tlvmc.gov.il
Investigator:
Last name:
Ravit Geva, Dr.
Email:
Principal Investigator
Facility:
Name:
Shamir Medical Center (Asaf Harofeh)
Address:
City:
Zerifin
Zip:
70300
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Nirit Yarom, MD
Email:
nirit.yarom@gmail.com
Contact backup:
Last name:
Sharona Ben-Ami
Phone:
+972-8-9778003
Email:
SharonaB@shamir.gov.il
Investigator:
Last name:
Nirit Yarom, MD
Email:
Principal Investigator
Start date:
June 13, 2024
Completion date:
January 2027
Lead sponsor:
Agency:
Lipomedix Pharmaceuticals Inc.
Agency class:
Industry
Source:
Lipomedix Pharmaceuticals Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06478862
