- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03823989
Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients
An Open-label, Phase 1b Study of Intravenously Administered Pegylated Liposomal Mitomycin C Lipid-based Prodrug (PROMITIL) in Combination With External Beam Radiotherapy in Patients With Advanced Cancer Requiring Palliative Radiotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
As combination with radiotherapy is expected to provide an additive or synergistic effect, the current dose-escalation study will begin with a dose of 1.25 mg/kg, to be followed by an increase (1.5 mg/kg) in Cohort 2 and a further increase 1.8 mg/kg in Cohort 3 in the absence of DLTs after two treatment cycles, with an interluding 10-fraction course of radiotherapy.
PROMITIL will be intravenously delivered on Day 1 of each of the two 21-day cycles.
Cohort 1: The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.
Cohort 2: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL. However, if 1 DLT is recorded, the second cohort of 6 patients will receive the same dose of 1.25 mg/kg PROMITIL. If 2 DLTs are recorded in Cohort 1, the second cohort of 6 patients will receive 1.0 mg/kg PROMITIL.
Cohort 3: If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study of the first 3 patients of Cohort 2, a third cohort will enroll 6 patients to receive treatment at a dose level of 1.8 mg/kg PROMITIL. If none or 1 DLT is recorded, the dose of 1.8 mg/kg will be cleared as recommended dose for phase 2. If 2 DLT are recorded, the study will be terminated as soon as the 2nd DLT is recorded, and the prior dose level of 1.5 mg/kg will be cleared as recommended dose for phase 2
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ashdod, Israel, 7747629
- Assuta Ashdod
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Jerusalem, Israel, 9112001
- Hadassah Medical Center
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Tel Aviv, Israel, 6971028
- Assuta Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with histologically or cytologically confirmed recurrent and/or metastatic, cancer, with at least one measurable lesion (≤10 cm diameter) on file, and with no definitive curative treatment option.
- A ≥21-day treatment-free interval from last chemotherapeutic treatment (including cytotoxic or non-cytotoxic myelosuppressive agents), and ≥14-day treatment-free interval from biological therapies consisting of CDK 4/6 inibitiors, PARP inhibitors, m-TOR inhibitors Hormonal therapies including LH-RH analogs or anagonists, tamoxifen, aromatase inhibitors, bicalutamide, aboraterone, corticosteroids, or enzalutamide may be continued uninterruptedly.
- No prior intravenous treatment with mitomycin-C either alone or in combination
- No prior extensive radiotherapy (e.g., whole pelvis, or greater than 50% of neuroaxis, whole abdomen, whole body or half-body) or bone marrow transplantation with high dose chemotherapy.
- No prior radiotherapy to the same anatomic site aimed for radiotherapy.
- Age ≥18years
- BMI: 18-36
- ECOG Performance Status ≤ 2
- Estimated life expectancy of at least 3 months
- Adequate bone marrow function (an absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5 g/dl, and a platelet count ≥100,000/mm3);
- Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤3× ULN, albumin ≥34g/L)
- Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥40 ml/min/1.73m2)
- Women of child-bearing potential practicing an acceptable method of birth control.
- Understanding of study procedures and willingness to comply for the entire length of the study and to provide written informed consent
Exclusion Criteria:
- Known hypersensitivity to the study drug or to any of its components
- Prior intravenous treatment with mitomycin C
- Patients requiring whole-brain irradiation
- Patients requiring re-irradiation of the same tumor/anatomical site.
- CHF (NYHA = Class IV)
- Severe COPD or Stage ≥3 severe emphysema with FEV1 between 30 and 50 percent of normal
- Chronic liver disease or cirrhosis with Child-Pugh Class C score
- Any other severe concurrent disease which in the judgment of the investigator would make the subject unsuitable for entry into this study
- History of human immunodeficiency virus (HIV) infection
- History of chronic active hepatitis including subjects who are carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless adequately treated and shown to be serum virus-free.
- Presence of uncontrolled infection.
- Evidence of active bleeding or bleeding diathesis
- Pregnant or lactating
- Treatment with other investigational drugs within <21 days of start of day 1 of study drug.
Uncontrolled ascites (defined as 2 or more palliative taps in the last 21 days before screening).
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Promitil 1.25 mg/kg
Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.25 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
|
The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.
If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL.
Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third cohort (n=6) will be recruited and will be treated with a dose level of 1.8 mg/kg.
Other Names:
A 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
Other Names:
|
Experimental: Promitil 1.5 mg/kg
Two treatment cycles, intravenous infusion of Promitil at a dosage of 1.5 mg/kg delivered at 21 days interval and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
|
The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.
If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL.
Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third cohort (n=6) will be recruited and will be treated with a dose level of 1.8 mg/kg.
Other Names:
A 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
Other Names:
|
Experimental: Promitil 1.8 mg/kg
two treatment cycles, intravenous infusion of Promitil at a dosage of 1.8 mg/kg delivered at 21 days interval (confirmatory cohort) and a 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
|
The first 6 patients recruited to the study will receive 1.25 mg/kg PROMITIL.
If no dose-limiting toxicities (DLTs) are recorded by day 43 of the study, the second cohort of 6 patients will begin treatment at a dose level of 1.5 mg/kg PROMITIL.
Upon completion of two treatment cycles, with ≤1 incident of DLTs in Cohort 2, a third cohort (n=6) will be recruited and will be treated with a dose level of 1.8 mg/kg.
Other Names:
A 10-fraction course of EBR (3 Gy/fraction), initiated 1-3 days after the first PROMITIL dose and completed within a 2-week period.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity (DLT) of Promitil in combination with external beam radiotherapy (EBR)
Time Frame: 6 weeks
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Report of Dose limiting toxicity
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6 weeks
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Incidence of Treatment-Emergent Adverse Events
Time Frame: 6 weeks
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Incidence all Adverse events of Promitil in combination with external beam radiotherapy (EBR)
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6 weeks
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To evaluate the response rate to PROMITIL in combination with external beam radiotherapy (EBR)
Time Frame: 7 weeks
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Local disease control in irradiated tumor areas at first reevaluation (Day 43-50), defined as rate of complete response [CR], partial response [PR] and stable disease [SD], as per RECIST 1.1 criteria
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7 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of response of the irradiated tumor site
Time Frame: 18 weeks
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Duration of response (in weeks) of the irradiated tumor site, from first evidence of response (Stable disease or better) to confirmed Progression disease (as per RECIST 1.1 criteria)
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18 weeks
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Progression-free survival (PFS)
Time Frame: 18 weeks
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Progression-free survival (PFS) (in weeks), from day of first dose of PROMITIL until confirmed Progression disease (as per RECIST 1.1 criteria)
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18 weeks
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Overall survival
Time Frame: 34 weeks
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Overall survival (in weeks), from day of first dose of PROMITIL to death of any cause
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34 weeks
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Plasma MLP level after Promitil infusion
Time Frame: 6 weeks (2 cycles of treatment)
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Plasma MLP levels before and after (1 h and 24 h) each PROMITIL dose
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6 weeks (2 cycles of treatment)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Adi Levy, MD, Hadassah Medical Organization
- Study Director: Eli Sapir, MD, Assuta Medical Center
Publications and helpful links
General Publications
- Tian X, Warner SB, Wagner KT, Caster JM, Zhang T, Ohana P, Gabizon AA, Wang AZ. Preclinical Evaluation of Promitil, a Radiation-Responsive Liposomal Formulation of Mitomycin C Prodrug, in Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2016 Nov 1;96(3):547-55. doi: 10.1016/j.ijrobp.2016.06.2457. Epub 2016 Jul 1.
- Tahover E, Bar-Shalom R, Sapir E, Pfeffer R, Nemirovsky I, Turner Y, Gips M, Ohana P, Corn BW, Wang AZ, Gabizon AA. Chemo-Radiotherapy of Oligometastases of Colorectal Cancer With Pegylated Liposomal Mitomycin-C Prodrug (Promitil): Mechanistic Basis and Preliminary Clinical Experience. Front Oncol. 2018 Nov 26;8:544. doi: 10.3389/fonc.2018.00544. eCollection 2018.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LIPORAD-2018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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