Cervical Cancer, KRAS Mutation-Related Tumors, Non-small Cell Lung Cancer, Ovarian Cancer, Soft-tissue Sarcoma, Triple Negative Breast Cancer
Conditions
Brief summary
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
DRUGSpedox-6
Given Intravenously (IV)
DRUGPegfilgrastim
Given Subcutaneous Injection or IV
DRUGFilgrastim
Given Subcutaneous Injection or IV
Sponsors
University of California, Irvine
Sunstate Biosciences LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by RECIST v1.1 | 2 Years | Sum of Complete Response (CR) and Partial Response (PR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR |
| Disease Control Rate (DCR) by RECIST v1.1 | 2 Years | Disease Control Rate (DCR) defined as Sum of Stable Disease (SD) + Partial Response (PR) + Complete Response (CR) by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD is defined as an increase of at least 20% in the sum of the longest diameters of the target lesions, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD) is defined as a tumor that has neither shrunk sufficiently to qualify as a partial response (PR) nor increased sufficiently to qualify as progressive disease (PD). |
| Complete Response Rate by RECIST v1.1 | 2 years | Complete Response Rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is defined as the disappearance of all target lesions. |
| Partial Response Rate by RECIST v1.1 | 2 years | Partial Response rate assessed by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stable Disease Rate by RECIST v1.1 | 2 years | Stable Disease Rate by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD is defined as an increase of at least 20% in the sum of the longest diameters of the target lesions, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD) is defined as a tumor that has neither shrunk sufficiently to qualify as a partial response (PR) nor increased sufficiently to qualify as progressive disease (PD). |
| Percentage of Responders by RECIST v1.1 | 2 years | Sum of Complete Response (CR) + Partial Response (PR) to determine Percentage of Responders by RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions; Complete Response (CR) is defined as the disappearance of all target lesions. Percentage of Responders (POR) = CR + PR |
| Overall Survival | 2 years | Survival rate of subjects who received at least one dose of Spedox-6. |
| Progression Free Survival | 2 years | Survival rate of subjects who received at least one dose of Spedox-6 without Progression of their disease. |
| Number of Patients with Grade 3 non-hematological toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | 2 years | Number of Patients who received at least one dose of Spedox-6 with Grade 3 non-hematological toxicities (excluding alopecia) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 with the following exceptions: Grade 3 nausea/vomiting or diarrhea \<72 hours with adequate antiemetic and other supportive care; Grade 3 fatigue \<1 week; Grade 3 electrolyte abnormality that lasts up to 72 hours, is not clinically complicated and resolves spontaneously or responds to conventional medical interventions. |
| Number of patients with Grade 4 non-hematologic (non-laboratory) by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 version 5.0 | 2 years | Number of patients who received at least one dose of Spedox-6 with Grade 4 non-hematologic (non-laboratory) toxicity of any duration per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| 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 | 2 years | Number of patients who received at least one dose of Spedox-6 with Grade 3 or Grade 4 febrile neutropenia of any duration per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| 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 | 2 years | Number of patients who received at least one dose of Spedox-6 with Grade 3 Thrombocytopenia in Combination with Grade 3 or greater blood and lymphatic system disorder per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| 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 | 2 years | Number of patients who received at least one dose of Spedox-6 with Grade 3 AST or ALT increase that is associated with a Grade 2 or greater Rise in Bilirubin per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
Countries
United States
Contacts
CONTACTChao Family Comprehensive Cancer Center University of California, Irvine
CONTACTUniversity of California Irvine Medical Center
PRINCIPAL_INVESTIGATORWarren Chow, MD
Chao Family Comprehensive Cancer Center
Outcome results
None listed