Promitil Treatment of Patients With Solid Tumors Associated With Deleterious Mutations Who Have Progressed After Therapy

NCT06478862 | Terminated Phase 2

• 1 other identifier: PROM-2301
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Cancer of Ovary; Pancreatic Ductal Adenocarcinoma

Keywords

Solid tumors; metastatic; inoperable; BRCA mutations

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) rate at Month 6

  defined as the proportion of patients who are alive and without radiological or clinical progression, based on RECIST 1.1

  24 weeks

Secondary Outcomes (6)

• Incidence, severity, and duration of treatment-emergent adverse events (TEAEs)

  30 weeks

• Objective response rate (ORR):

  24 weeks

• Duration of response (DOR)

  24 weeks

• Disease control rate (DCR)

  24 weeks

• Overall survival (OS):

  52 weeks

Other Outcomes (1)

• Plasma MLP (mitomycin lipidic pro-drug) level after Promitil infusion

  12 weeks

Study Arms (2)

Pancreatic cancer

EXPERIMENTAL

Eligible subjects with pancreatic cancer will be intravenously (IV) administered 2.0 mg/kg Promitil on Day 1 of each 28-day cycle, for up to 6 cycles. Each cycle may be extended for up to 3 additional weeks (i.e., up to a total of 7 weeks from previous Day 1), if tolerability issues arise.

Drug: Promitil

Ovarian cancer

EXPERIMENTAL

Eligible subjects with ovarian cancer will be intravenously (IV) administered 2.0 mg/kg Promitil on Day 1 of each 28-day cycle, for up to 6 cycles. Each cycle may be extended for up to 3 additional weeks (i.e., up to a total of 7 weeks from previous Day 1), if tolerability issues arise.

Drug: Promitil

Interventions

Promitil DRUG

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.

Also known as: Pegylated Liposomal Mitomycin-C Lipid-based Prodrug

Ovarian cancer; Pancreatic cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older on day of consent
• Patient with either one of the following histologically or cytologically confirmed, deemed incurable malignancies:
• Recurrent ovarian cancer
• Inoperable, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC)
• 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)
• 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
• 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
• Capable of providing written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• ECOG performance status of 0 or 1
• Adequate organ function as defined by:
• Absolute neutrophil count (ANC) ≥ 1500/µL
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 9.5 g/dL
• Hematocrit ≥30%
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

You may not qualify if:

• 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
• Any other severe concurrent disease which, in the judgment of the investigator, would make the subject unsuited for treatment
• 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
• Evidence of active bleeding
• 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
• Patient is pregnant or lactating
• Prior intravenous treatment with MMC, either alone or in combination
• Other anti-cancer treatment within 2 weeks before start of study drug
• Other myelosuppressive treatment within 4 weeks before start of study drug
• Treatment with other investigational drugs within 5 drug half-lives of day 1 of study drug
• Patients with uncontrolled ascites that had more than one palliative abdominal tap up to 30 days prior to Screening

Sponsors & Collaborators

• Lipomedix Pharmaceuticals Inc.: lead

Study Sites (6)

Soroka Medical Center

Beersheba, Israel

Location

Rambam Health Care Campus

Haifa, Israel

Location

Wolfson Medica Center

Holon, 5822012, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Shamir Medical Center (Asaf Harofeh)

Ẕerifin, 70300, Israel

Location

Related Publications (2)

• Gabizon A, Shmeeda H, Tahover E, Kornev G, Patil Y, Amitay Y, Ohana P, Sapir E, Zalipsky S. Development of Promitil(R), a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside. Adv Drug Deliv Rev. 2020;154-155:13-26. doi: 10.1016/j.addr.2020.07.027. Epub 2020 Aug 7.

  PMID: 32777239 BACKGROUND

• Gabizon AA, Tahover E, Golan T, Geva R, Perets R, Amitay Y, Shmeeda H, Ohana P. Pharmacokinetics of mitomycin-c lipidic prodrug entrapped in liposomes and clinical correlations in metastatic colorectal cancer patients. Invest New Drugs. 2020 Oct;38(5):1411-1420. doi: 10.1007/s10637-020-00897-3. Epub 2020 Jan 18.

  PMID: 31955309 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ora Rosengarten, MD

  Shaare Zedek

  PRINCIPAL INVESTIGATOR

• Ofer Purim, MD

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

• Ravit Geva, MD

  Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

• Amichai Meirovitz, MD

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

• Ruth Peretz, MD

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

• Nirit Yarom, MD

  Asaf Harofeh Medical Center

  PRINCIPAL INVESTIGATOR

• Tali Levy, MD

  Wolfson Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: June 27, 2024
• Study Start: June 13, 2024
• Primary Completion: January 2, 2026
• Study Completion: January 2, 2026
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (6)