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

Malignant Solid Tumour Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01337505
• Other study ID #: INNO-206-P1-MTD-01
• Status: Completed
• Phase: Phase 1
• Start date: April 2011
• Est. completion date: December 2012

Study information

• Verified date: February 2013
• Source: ImmunityBio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Solid Tumour
• Neoplasms

Intervention

Drug:
• INNO-206
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.

Locations

Country	Name	City	State
United States	Sarcoma Oncology Center	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
ImmunityBio, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)