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

University of California Irvine (UCI)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: KRAS Mutation-Related Tumors; Non-small Cell Lung Cancer; Soft-tissue Sarcoma; Ovarian Cancer; Triple Negative Breast Cancer; Cervical Cancer

Treatments: Drug: Spedox-6; Drug: Filgrastim; Drug: Pegfilgrastim

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07064018

6228

UCI 24-08 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 67 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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67 participants in 8 patient groups

Phase 1b Dose Level 1 - Spedox-6

Experimental group

Description:

Spedox-6, 20 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.

Treatment:

Drug: Spedox-6

Phase 1b Dose Level 2 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 40 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 3 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 80 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 4 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 120 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 5 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 160 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 6 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 200 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 7 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 250 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6

Phase 1b Dose Level 8 - Spedox-6 + Filgrastim/Pegfilgrastim

Experimental group

Description:

Spedox-6, 310 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles. Filgrastim or Pegfilgrastin, injected subcutaneously or intravenously, received according to Institutional standard.

Treatment:

Drug: Pegfilgrastim

Drug: Filgrastim

Drug: Spedox-6