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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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).

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1b Dose Level 1 - Spedox-6 		Spedox-6, 20 mg/m2, Chemotherapy single agent systemic, received on day 1 of each 21 day cycle, for a total of 6 cycles.
  • Drug: Spedox-6
    Given Intravenously (IV)
Experimental
Phase 1b Dose Level 2 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 3 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 4 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 5 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 6 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 7 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV
Experimental
Phase 1b Dose Level 8 - Spedox-6 + Filgrastim/Pegfilgrastim 		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.
  • Drug: Spedox-6
    Given Intravenously (IV)
  • Drug: Pegfilgrastim
    Given Subcutaneous Injection or IV
  • Drug: Filgrastim
    Given Subcutaneous Injection or IV

Recruiting Locations

Chao Family Comprehensive Cancer Center University of California, Irvine
Orange, California 92868
Contact:
Warren Chow, MD
877-827-8839
ucstudy@uci.edu

More Details

Status
Recruiting
Sponsor
University of California, Irvine

Study Contact

Chao Family Comprehensive Cancer Center University of California, Irvine
1-877-827-8839
ucstudy@uci.edu