Clinical trial NCT03199586: Clinical Trial of Metastasis Inhibitor NP-G2-044 in Patients With Advanced or Metastatic Treatment-Refractory Solid Tumor Malignancies
Official title: First-in-Human, Dose Finding, Open Label Phase 1A-1B Clinical Trial of Metastasis Inhibitor NP-G2-044 in Patients With Advanced or Metastatic Treatment-Refractory Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Pancreas Cancer
Prostate Cancer
Lung Cancer
Colon Cancer
Esophagus Cancer
Liver Cancer
Ovary Cancer
Advanced or Metastatic Treatment-refractory Solid Tumor Malignancies
Keywords: Advanced or metastatic treatment-refractory solid tumor malignancies
Lead sponsor: Novita Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Translational Drug Development
First posted: 2017-06-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 1 A: First-in-human phase 1 study to determine safety of NP-G2-044 when given orally on a daily X 28 days followed by a 14 day rest period.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent and mental capability to understand the informed consent
2. Male or female patients \> 18 years of age
3. Histologically or cytologically documented locally advanced or metastatic solid tumor malignancies either treatment-refractory or otherwise ineligible for treatment with standard-of-care agents/regimens
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
5. Evaluable or measurable disease per RECIST v1.1
6. Life expectancy \> 3 months
7. ECG without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the Investigator
8. Acceptable organ and marrow function as defined below:

   * Absolute neutrophil count \> 1,500 cells/μL
   * Hemoglobin ≥ 9.0 g/dL
   * Platelets \> 100,000 cells/μL
   * Total bilirubin ≤ 1.5 mg/dL
   * Albumin ≥ 3 g/dL
   * Aspartate aminotransferase (AST)/alanine transaminase (ALT)/alkaline phosphatase (ALP)/Gamm-glutamyl transferase (GGT) ≤ 2.5 times ULN. For Phase 1A only, if liver metastases are present, AST/ALT/ALP \< 5 times ULN
   * Serum creatinine \< 1.5 mg./dL and a measured creatinine clearance ≥ 60 mL/min
   * Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN
9. Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy test prior to first dose of study drug.
10. Male and female patients with reproductive potential must agree to use adequate contraceptive precautions throughout the study.

Exclusion Criteria:

1. Chemotherapy, radiotherapy or other anti-cancer treatment within 4 weeks or 5 half-lives (whichever is shorter) (6 weeks for nitrosoureas or mitomycin C) of the first dose of study drug or patients who in opinion of Investigator have not recovered from AEs due to agents administered greater than 4 weeks earlier (prior immunotherapy is allowed)
2. Participation in any other clinical investigation using an experimental drug within 4 weeks of first dose of study drug
3. Failure to recover to ≤ grade 1 toxicity (except grade 1-2 alopecia or neuropathy) associated with previous chemotherapy, radiotherapy, biologic, hormone or prior investigational therapy
4. Known untreated brain metastases or treated brain metastases that have not been radiographically and clinically stable (i.e. not requiring steroids) ≥ 4 weeks prior to study enrollment
5. Baseline prolongation of QT/QTc interval (QTc interval \> 470 msec in women and \>450 msec in men)
6. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that in opinion of Investigator would limit compliance with study requirements
7. Women who are pregnant or breastfeeding
8. Prior allogenic hematopoietic stem cell transplant or allogenic bone marrow transplant or prior solid organ transplant or current use of immuno suppression drugs or anti-transplant rejection drugs
9. Prior history of clinically significant gastrointestinal bleeding, intestinal obstruction or gastrointestinal perforation within 6 months of study enrollment
10. Sponsor reserves right to exclude any patient from the study on basis of pre-study medical histories, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria

Primary outcomes:
measure: Establish the safe recommended phase 2 dose
timeFrame: 24 months
Secondary outcomes:
measure: Identify and characterize preliminary anti tumor activity
timeFrame: 24 months
measure: Characterize the pharmacokinetics of NP-G2-044
timeFrame: 24 months
measure: Tmax
timeFrame: 24 months
measure: Cmax
timeFrame: 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: New York
country: United States
facility: Memorial Sloan Kettering Hospital
state: New York
Study officials:
affiliation: Novita Pharmaceuticals
name: Jillian Zhang, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Sever S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol. 2021 Sep;36(9):2607-2614. doi: 10.1007/s00467-020-04812-z. Epub 2020 Nov 13.