Trial of Single Protein Encapsulated Doxorubicin, SPEDOX-6 in Advanced Malignancies

Official title

Phase Ib/IIa Trial of Single Protein Encapsulated Doxorubicin, SPEDOX-6 in Advanced Malignancies

Overview

This is a Phase 1b/IIa dose escalation clinical trial determining the recommended phase II dose of SPEDOX-6 in subjects with advanced, therapy-refractory soft-tissue sarcoma (STS); triple-negative breast cancer (TNBC); Non-small cell lung cancer (NSCLC); cervical cancer; ovarian cancer; KRAS mutant pancreatic ductal adenocarcinoma. These are subjects who have not previously been treated with anthracyclines.

Interventions

• Drug Spedox-6
  Given Intravenously (IV)
• Drug Pegfilgrastim
  Given Subcutaneous Injection or IV
• Drug Filgrastim
  Given Subcutaneous Injection or IV

Primary outcome measures

• Overall Response Rate (ORR) by RECIST v1.1 [Time frame: 2 Years]
• Disease Control Rate (DCR) by RECIST v1.1 [Time frame: 2 Years]
• Complete Response Rate by RECIST v1.1 [Time frame: 2 years]
• Partial Response Rate by RECIST v1.1 [Time frame: 2 years]

Secondary outcome measures (9)

• Stable Disease Rate by RECIST v1.1 [Time frame: 2 years]
• Percentage of Responders by RECIST v1.1 [Time frame: 2 years]
• Overall Survival [Time frame: 2 years]
• Progression Free Survival [Time frame: 2 years]
• Number of Patients with Grade 3 non-hematological toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [Time frame: 2 years]
• Number of patients with Grade 4 non-hematologic (non-laboratory) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [Time frame: 2 years]
• Number of patients with Grade 3 or Grade 4 febrile neutropenia by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [Time frame: 2 years]
• Number of patients with Grade 3 Thrombocytopenia in Combination with Grade 3 or greater blood and lymphatic system disorder by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [Time frame: 2 years]
• Number of patients with Grade 3 AST or ALT increase that is associated with a Grade 2 or greater Rise in Bilirubin by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Subjects ≥ 18 years at the first screening examination/visit.
• Subjects with advanced histologically or cytologically confirmed solid tumors (see below) refractory to or relapse from at least two previous therapies.
• Tumor types expected to express lower levels of FcRn relative to normal tissue including: STS, TNBC, cervical cancer, NSCLC, ovarian cancer, and KRAS mutated pancreatic ductal adenocarcinoma without requirement for testing FcRn level.
• Disease that is considered measurable by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy of at least 12 weeks.
• Human Immunodeficiency Virus (HIV)-positive trial participants should be on established antiretroviral therapy (ART) for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment.
• Left ventricular ejection fraction > 50%.
• Adequate organ function: (Hb ≥10 g/dL, ANC ≥1,000/µL3, and platelets

≥100,000/µL3), serum bilirubin ≤.5x the institutional upper limit of normal (ULN) (unless known Gilbert's disease), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤3x ULN, and creatinine clearance >50 mL/min as assessed by Cockcroft-Gault equation.

• For patients with known Gilbert's disease, serum unconjugated bilirubin must be < 4 mg/dL.
• Patient must have washed out of prior chemotherapy (at least 3 weeks from last end of therapy), radiotherapy (at least 4 weeks from last end of therapy), immunotherapy (at least 4 weeks from last end of therapy), other targeted therapies (at least 4 weeks from last end of therapy), or surgery (at least 4 weeks).
• Recovery from toxicities of prior therapy. Toxicities should have recovered to CTCAE grade ≤ 1 or baseline with exception of alopecia.
• Females of reproductive potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment. Additionally, female subjects of reproductive potential should agree to use effective acceptable forms of contraception: surgical sterilization (tubal ligation); total abstinence from sexual intercourse with the opposite sex; established hormonal birth control (e.g., oral, transdermal, injection, or implant) plus a barrier method or a double barrier method (intrauterine device, spermicide, or a diaphragm plus condom) for at least 1 month prior to Cycle 1 Day 1 and agreement to use such a method during study participation and for an additional 6 months after the last dose of SPEDOX-6.
• For males of reproductive potential: vasectomy or highly effective contraception (e.g., condoms, abstinence) during the study and for an additional 6 months after the last dose of SPEDOX-6.

Exclusion criteria

• Patients with cancers with known driver mutations for which there are known and effective targeted therapies that have not received those therapies, but are able to. If a patient has received appropriate targeted treatment for their mutations and progressed, or those treatments are contraindicated, they will be considered potentially eligible.
• Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months before study entry.
• Untreated metastases to the Central Nervous System (CNS).
• Have received any prior doxorubicin or anthracycline equivalent.
• Previous radiation to the mediastinal or pericardial area.
• A known allergy to albumin.
• HIV infection with CD4+ count < 350 cells/µL or Acquired Immunodeficiency (AIDS)-defining opportunistic infection in previous 12 months.
• Pregnant (positive serum or urine pregnancy test) or lactating.
• Previous treatment with an investigational agent or the non-approved use of a drug or device withing 4 weeks of study entry.
• Uncontrolled diabetes mellitus.
• Patients who require concomitant use of strong inhibitors or inducers of CYP3A4, CYP2D6 or P-glycoprotein (P-gp).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Chao Family Comprehensive Cancer Center University of California, Irvine — Orange

Identifiers

NCT: NCT07064018 · 6228 · UCI 24-08

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗