An Open Phase 1B Study for Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Oxaliplatin-based Chemotherapy in Patients With Gastro-intestinal Malignancies

PROMIFOX

This single center, Phase 1b, prospective, dose limiting toxicity (DLT)-clearing study, will assess the safety and efficacy of intravenously administered PROMITIL in combination with FOLFOX in cancer patients with inoperable, locally advanced or metastatic GI solid tumors. Based on previous clinical results, we hypothesized that the addition of PROMITIL to FOLFOX, a treatment protocol consisting of oxaliplatin and fluoropyrimidine and commonly used to treat gastrointestinal (GI) malignancies, may enhance the overall efficacy of this combination regimen while maintain a reasonable safety profile.

2021-01-13

2023-09-10

2023-09-12

Terminated

Early phase I

9

Inclusion Criteria: 1. Patients with histologically or cytologically confirmed diagnoses of GI malignancies, deemed incurable (inoperable and locally advanced or metastatic), and X-ray computed tomography (CT)-evaluable (measurable or non-measurable) disease, with or without contrast enhancement Patients must have one the following carcinomas (including adenocarcinomas, signet ring cell, and mucinous carcinomas) to be eligible to be included in the study: 1. Esophagus (non-squamous) and GE junction 2. Stomach 3. Hepatocellular carcinoma 4. Pancreas (exocrine) and ampulla 5. Cholangiocarcinoma (intra-hepatic) 6. Bile ducts and gall bladder 7. Small bowel 8. Large bowel 9. Rectum 2. Age 18-year or older 3. ECOG Performance Status ≤ 2 4. Estimated life expectancy of at least 3 months 5. Adequate bone marrow function (absolute neutrophil count ≥1500/mm3, hemoglobin ≥9.5 g/dl, and a platelet count ≥100,000/mm3 6. Adequate liver function (serum bilirubin ≤2.0 mg/100 ml; alanine aminotransferase ≤3× upper limit of normal \[ULN\], albumin ≥30 g/L, normal INR of prothrombin time (unless on coumadin treatment) 7. Adequate renal function (serum creatinine ≤1.5 mg/100 ml or creatinine clearance ≥45 ml/min/1.73m2). 8. A ≥21-day treatment-free interval from chemotherapeutic treatment, with the exception of 5-FU, capecitabine and biological therapies, where ≥14-day treatment-free intervals suffice. 9. No other myelosuppressive treatment within 4 weeks of initiation of the study drug. 10. No prior intravenous treatment with mitomycin-C, either alone or in combination 11. No prior oxaliplatin treatment for inoperable locally advanced or metastatic disease 12. A ≥6-month treatment-free interval from oxaliplatin, if given as adjuvant therapy or as neoadjuvant therapy for potentially operable disease 13. No prior extensive radiotherapy (e.g., whole pelvis, total neuroaxis or greater than 50% of neuroaxis, whole abdomen, whole body or half body) or bone marrow transplantation with high-dose chemotherapy and/or total body irradiation. 14. Women of child-bearing potential must be practicing an acceptable method of birth control. 15. Understanding of study procedures and willingness to comply throughout the entire course of the study and to provide written informed consent Exclusion Criteria: 1. Patients with squamous cell cancer, stromal tumor, sarcoma, neuroendocrine tumor 2. Known hypersensitivity to the study drugs or to any of their components 3. Cirrhosis (Child-Pugh Class C score) 4. Serum albumin level \< 3.0 g/dl 5. Any other severe concurrent disease, which in the judgment of the investigator, would make the subject inappropriate for entry into this study 6. History of human immunodeficiency virus (HIV) infection 7. History of chronic active hepatitis, including subjects who are carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV). 8. Uncontrolled diabetes: HgbA1C≥7.5%, 9. Presence of uncontrolled infection 10. Evidence of active bleeding or bleeding diathesis 11. Untreated (no surgery, no radiation) brain metastases, whether patient is symptomatic or asymptomatic. Patients with brain metastases treated by surgery or radiation who are stable and symptom-free requiring ≤4 mg dexamethasone/day, are eligible. 12. Pregnant or lactating women 13. Treatment with other investigational non-myelosuppressive drugs within 14 days of start of the study drug, and/or with myelosuppressive agents within 28 days of start of the study drug. 14. Uncontrolled ascites (defined as 2 or more palliative taps within 30 days of screening

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'There will be up to two cohorts, with six subjects per cohort. Eligible subjects will be consecutively assigned, in order of accrual, to receive three cycles of PROMITIL-FOLFOX treatment. Dosing regimens will begin with cohort 1 (PROMITIL dose of 1.6 mg/kg).Dose limiting toxicity (DLT) for the combination treatment will be considered cleared if fewer than two patients per cohort experience DLT events during the first two cycles of treatment. Dose escalation to cohort 2 (PROMITIL dose of 2mg/kg) will be authorized after 5 or 6 patients of cohort 1 have completed the second cycle with DLT detected in fewer than two patients. If ≥2 patients of Cohort 1 develop DLT, dose escalation will be halted and Cohort -1 (PROMITIL dose of 1.2 mg/kg) will be opened. Should ≥2 patients in Cohort -1 or Cohort 2 experience DLT events, the study will be discontinued.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ACTUAL'}}

2023-09-14