Safety and Maximum Tolerated Dose (MTD) Study of INNO-206 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase 1b open-label study evaluating the preliminary safety and maximum tolerated dose of a new formulation of INNO-206 administered at doses of 230 mg/m2, 350 mg/m2 and 450 mg/m2 (165, 260, 325 mg/m2 doxorubicin equivalents, respectively) through intravenous infusion on Day 1 every 21 days for up to 6 cycles.

Official Title
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An Open-Label Phase 1 Study to Investigate the Safety and Maximum Tolerated Dose of INNO-206 (Doxorubicin-6-Maleimidocaproyl Hydrazone; DOXO-EMCH) Administered as a 30 Minute Infusion Every 3 Weeks in Subjects With Advanced Solid Tumors

Conditions
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Malignant Solid Tumour

Intervention / Treatment
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* Drug: INNO-206


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 70 years, male or female. Histologically or cytologically confirmed malignant solid tumor that has relapsed or is refractory to standard therapy. Subjects who have received prior radiation therapy with stable CNS metastasis with no progression of brain metastasis by CT/MRI scan in last 4 weeks. Capable of providing informed consent and complying with trial procedures. ECOG performance status 0-2. Life expectancy >12 weeks. Measurable or evaluable disease according to RECIST 1.1 criteria. Women must not be able to become pregnant (e.g. post menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating. Geographic accessibility to the site. Exclusion Criteria: Palliative surgery, chemotherapy, immunotherapy and/or radiation less than 4 weeks prior to the Screening Visit. Exposure to any investigational agent within 30 days of the Screening Visit. Laboratory values: Screening serum creatinine greater than or equal to 1.5 mg/dL, alanine aminotransferase (ALT) greater than 3 times the upper limit of normal, total bilirubin greater than 3 times the upper limit of normal, white blood cell (WBC) count < 3500/mm3, absolute neutrophil count < 2000/mm3, platelet concentration < 100,000/mm3, hematocrit level < 33% for females or < 35% for males, or coagulation tests (PT,PTT) >1.5 times the upper limit or normal. Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines. Serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V. History or signs of active coronary artery disease with or without angina pectoris. Serious myocardial dysfunction defined scintigraphically (MUGA, myocardial scintigram)or ultrasound determined absolute left ventricular ejection fraction (LVEF) < 45% of predicted. History of HIV infection. Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or antifungals. Major surgery within 3 weeks prior to treatment. Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results. Any condition that is unstable and could jeopardize the subject's participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INNO-206<br>INNO-206 at dosages of 230, 350, and 450 mg/m2 doxorubicin equivalents of 165, 260, and 325 mg/m2)will be administered as a 30 minute IVI on Day 1 of each cycle. | Drug: INNO-206<br>* INNO-206 at dosages of 230, 350, and 450 mg/m2 (doxorubicin equivalents of 165, 260, and 325 mg/m2) will be administered as a 30 minute IVI on Day 1 of each cycle.<br>* Other names: DOXO-EMCH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety will be based on adverse events, tolerability, physical examinations, vital signs, ECG results, laboratory test results. MTD: If 2 of 5 subjects an any dose level experiences a grade 3 or 4 non-hematologic toxicity, or a platelet count <25,000/uL or a neutrophil count <500/uL lasting >7 days and/or associated with fever >38.5C, 3 more subjects will be entered at that dose level. If 2 of 3 of the additional subjects experience any of the above adverse events, the dose level immediately below will be identified as the MTD. | Up to 6 cycles (every 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | To evaluate the objective response reate (OR; RECIST 1.1 criteria). Changes in tumor measurements from baseline values that are confirmed by repeat assessments will be assigned a status of CR or PR. OR=CR+PR. | Up to 6 cycles (every 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INNO-206, Phase 1, DOXO-EMCH, Advanced solid tumors