A Non-randomized, Open-label, Multi-centric Dose-finding Adaptive Phase I/IIa Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Repeated Intravenous IPP-204106N Administrations in Adult Patients With Advanced Solid Tumors
- Signed informed consent obtained prior to initiation of any study-specific procedures
for study participation and signed informed consent for tumor biopsy. Informed
consent for tumor biopsy is mandatory for patients included in the phase IIa part of
- Man or woman at least 18 years of age.
- Histological or cytological confirmed advanced solid tumor, non eligible for curative
local treatment or active palliation with systemic therapy.
- 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.
- 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.
- Tumor biopsy available at study entry for patients included in the phase IIa part of
the study and if possible for phase I patients.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Life expectancy more than 3 months according to the investigator's judgment.
- 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.
- Adequate hematological counts: neutrophils >=1.5 x 109/L, platelets >=100 x 109/L,
hemoglobin >=9 g/dL.
- Adequate renal function: serum creatinine ≤1.5 × upper limit of normal range (ULN).
- Adequate hepatic function:
- Serum bilirubin ≤1.5 × ULN (except for isolated hyperbilirubinemia attributed to
- Alkaline phosphatase, aspartate aminotransferase (ASAT), alanine
aminotransferase (ALAT) ≤2.5 × ULN (or ≤5 × ULN in case of liver metastases).
- 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.
- Hematological malignancy (including lymphomas).
- 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
- Ongoing cardiac arrhythmias of NCI-CTCAE grade ≥2.
- Active uncontrolled infections.
- Uncontrolled hypertension.
- Radiotherapy or chemotherapy within 4 weeks before study entry (6 weeks for
nitrosoureas or mitomycin).
- Pregnancy or breastfeeding.
- Participation to another therapeutic clinical trial within the last 4 weeks except
studies including treatment with N6L.
- History of severe allergic reactions.
- Documented or suspected allergy to any nucleolin antagonist.
- Documented allergy to excipient (mannitol or chondroitin sulfate) product.