Solid tumors MedDRA version: 16.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Interventions
Product Name: IPP-204106
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: N6L
Other descriptive name: Nucant6L
Sponsors
Elro Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent obtained prior to initiation of any study-specific procedures for study participation and signed informed consent for tumor biopsy and 18FDG PET-CT complementary study. Informed consent for tumor biopsy is mandatory for patients included in the phase IIa part of the study. Informed consent for 18FDG PET-CT study concerns phase I and IIa patients but is not mandatory. 2. Man or woman at least 18 years of age. 3. Histological or cytological confirmed advanced solid tumor, non eligible for curative local treatment or active palliation with systemic therapy. 4. Patients with measurable or evaluable disease (by tumor measurements or by tumor biomarker) with a proof of disease progression. At least one measurable lesion is mandatory for the phase IIa portion of the study. 5. Patients currently under treatment with N6L or patients who have taken part in the Phase I part of the study are eligible for the phase IIa part, according to the investigator’s judgment, irrespective of their tumor status. 6.Tumor biopsy available at study entry for patients included in the phase IIa part of the study and if possible for phase I patients. 7. Eastern Cooperative Oncology Group (ECOG) performance status =2. 8. Life expectancy more than 3 months according to the investigator’s judgment. 9. Recovery from any acute toxicity related to prior therapy. Toxicity should be =grade 1 according to NCI-CTCAE criteria or returned to baseline excluding alopecia. 10.Adequate hematological counts: neutrophils =1.5 x 10^9/L, platelets = 100 x 10^9/L, hemoglobin = 9 g/dL. 11. Adequate renal function: serum creatinine =1.5 × upper limit of normal range (ULN). 12. Adequate hepatic function: • Serum bilirubin =1.5 × ULN (except for isolated hyperbilirubinemia attributed to Gilbert’s syndrome). • Alkaline phosphatase (or = 5 x ULN in case of liver or bone metastases), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) =2.5 × ULN (or =5 × ULN in case of liver metastases). 13. All women of child-bearing potential must use adequate contraception throughout the duration of the study, or their partner must be surgically sterilized. The pre-study pregnancy test must be negative for women with reproductive potential. Women who have been surgically sterilized or are at least two years post-menopausal may be enrolled and do not need birth control. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Hematological malignancy (including lymphomas). 2. Any of the following within the 6 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, stroke, including transient ischemic attack, or pulmonary embolism. 3. Ongoing cardiac arrhythmias of NCI-CTCAE grade =2. 4. Active uncontrolled infections. 5. Uncontrolled hypertension. 6. Radiotherapy or chemotherapy within 4 weeks before study treatment (6 weeks for nitrosoureas or mitomycin). 7. Pregnancy or breastfeeding. 8. Participation to another therapeutic clinical trial within the last 4 weeks except studies including treatment with N6L. 9. History of severe allergic reactions. 10. Documented or suspected allergy to any nucleolin antagonist. 11. Documented allergy to excipient (mannitol or chondroitin sulfate) product 12. Documented allergy to Aspirin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • The primary objective of the phase I part of the study is to determine the recommended optimal dose of intravenous IPP-204106N administered daily for at least 5 consecutive days (Days 1 to 5) with a wash-out period of 2 weeks, to adult patients with advanced solid tumors. • The primary objective of the phase IIa part of the study is to search for early evidence of anti-tumor activity of IPP-204106N at the optimal dose, based on RECIST criteria or biomarkers analysis in adult patients with advanced solid tumors.;Secondary Objective: • To evaluate the overall safety of IPP-204106N. • To determine the pharmacokinetic (PK) profile of IPP-204106N during the dose-escalation phase of the study. • To evaluate the tumor response rate, duration of objective responses and stabilizations. • To evaluate the tumor growth rate (GR). • To evaluate the time to progression (TTP) and progression-free survival (PFS) of IPP-204106N at the recommended dose. • To identify genomic and proteomic tumor biomarkers. • To evaluate the early metabolic effects of IPP-204106N as measured by serial fluorine 18 fluorodeoxyglucose positron emission tomography - computed tomography (18FDG PET-CT) (descriptive analysis) at both time points during the treatment cycle and to evaluate the correlation between the early 18FDG PET-CT response and standard RECIST 1.1 or biomarker analysis and the correlation between the early 18FDG PET-CT response and TTP and PFS at the recommended dose.;Primary end point(s): The primary endpoint is a composite (combined) toxicity/pharmacokinetic criterion defined as: • Toxicity assessed during cycle 1: number of patients experiencing a dose limiting toxicity (DLT) according to the NCI-CTCAE (v 4.0, May 2009), defined as: o Hematological drug-related toxicity: grade 4 neutropenia =7 days, grade 4 thrombocytopenia, grade 3 thrombocytopenia with hemorrhage/bleeding, and febrile neutropenia. o Nausea, vomiting or diarrhea grade =3 despite optimal treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall safety of IPP-204106N: AE, SAE, vital signs, laboratory hematological and biochemical assessments. • Pharmacokinetic profile of IPP-204106N during the dose-escalation phase. • Anti-tumor activity of IPP-204106N: tumor objective responses according to RECIST criteria (version 1.1), duration of objective responses and stabilizations. • Tumor growth rate • Time to progression and progression-free survival at the recommended dose. • Identification of genomic and proteomic tumor biomarkers. • Early metabolic effects of IPP-204106N as measured by serial 18FDG PET-CT (descriptive analysis) at both time points during the treatment cycle and evaluation of the correlation between the early 18FDG PET-CT response and standard RECIST 1.1 or biomarker analysis and the correlation between the early 18FDG PET-CT response and TTP and PFS at the recommended dose.;Timepoint(s) of evaluation of this end point: Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 12/15 | — |
Countries
Belgium
Contacts
Public ContactZimmer
Elro Pharma
Outcome results
None listed