Clinical trial NCT02240238: Combination Therapy With NC-6004 and Gemcitabine in Advanced Solid Tumors or Non-Small Cell Lung, Biliary and Bladder Cancer
Official title: A Phase 1b/2 Dose Escalation and Expansion Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients With Advanced Solid Tumors or Non-Small Cell Lung, Biliary Tract, and Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Lead sponsor: NanoCarrier Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-09-15
Enrollment: 119
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: In the dose escalation phase (Part 1), this study will determine the dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD) and recommended Phase 2 (RPII) dose of NC 6004 in combination with gemcitabine.

In the expansion phase of the study (Part 2), study will evaluate the activity, safety, and tolerability at the RPII dose identified in Part 1 in patients with squamous NSCLC, biliary tract, and bladder cancer.


Eligibility criteria: Inclusion Criteria:

* (Part 1 only) Have a histologically or cytologically confirmed diagnosis of advanced solid tumor that has relapsed or is refractory to standard curative or palliative therapy or has a contraindication to standard therapy.
* (Part 2 only) Cohort 1: Have histologically or cytologically confirmed diagnosis of Stage IV squamous NSCLC and have not received prior chemotherapy or immunotherapy for metastatic disease and are not known to be PD-L1 positive (known high PD-L1 expression defined as Tumor Proportion Score \[TPS\] greater than or equal to 50%). Patients with known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene must have received at least 1 and up to 2 targeted therapies prior to enrollment.
* (Part 2 only) Cohort 2: Have histologically or cytologically confirmed diagnosis of nonresectable, recurrent, or metastatic biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma) and have not received prior systemic anticancer therapy for advanced or metastatic disease.
* (Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery.
* Have measurable disease per RECIST version 1.1.
* Have an ECOG PS of 0 to 1, with the exception of patients in Part 2 (Cohort 3, unfit bladder cancer patients) who may have an ECOG PS of 2
* Adequate bone marrow reserve, liver and renal function
* Have a negative pregnancy test result at Screening for females of childbearing potential
* Male patients must agree to use a condom during treatment and for 90 days after dosing and must agree not to donate sperm for 90 days after dosing
* Women of childbearing potential are willing to agree to use 1 of the study defined effective methods of birth control from the time of study entry to 6 months after the last day of treatment
* Reasonably recovered from preceding major surgery as judged by the investigator or no major surgery within 4 weeks prior to the start of Day 1 treatment

Exclusion Criteria:

* Have received prior platinum therapy in the past 3 months (Part 1) or 6 months in the adjuvant or neoadjuvant setting (Part 2).
* Have received prior cisplatin and gemcitabine concomitantly within the last 6 months or are refractory to cisplatin and gemcitabine.
* Unresolved toxicity from prior radiation, chemotherapy, or other targeted treatment, including investigational treatment
* Have evidence suggesting pulmonary fibrosis or interstitial pneumonia.
* Have a history of thrombocytopenia with complications
* Have known hypersensitivity to platinum compounds or gemcitabine.
* Have uncontrolled diabetes or have hypertension requiring more than 3 medications for control of hypertension.
* Have pre-existing alcoholic liver injury or significant liver disease.
* Pregnant or breast feeding

Primary outcomes:
measure: Determine the RPII Dose of NC-6004 in Combination With Gemcitabine
timeFrame: 1 year
measure: Activity of NC-6004 Measured by Progression-free Survival (PFS)
timeFrame: 1 year
Secondary outcomes:
measure: ORR
timeFrame: Up to 40 weeks
measure: DCR
timeFrame: Up to 40 weeks
measure: DOR
timeFrame: every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.
measure: OS
timeFrame: every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.
measure: EORTC QLQ-C30
timeFrame: 1 year
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Serdika EOOD
state: Sofia-Grad
city: Shumen
country: Bulgaria
facility: Complex Oncology Center - Shumen EOOD
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
city: Krakow
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
city: Poznan
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Bucharest
country: Romania
facility: Coltea Clinical Hospital
city: Cluj-Napoca
country: Romania
facility: Prof Dr I Chiricuta Institute of Oncology
city: Craiova
country: Romania
facility: Oncology Center Sfantul Nectarie
city: Iasi
country: Romania
facility: Euroclinic Oncology Center SRL
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
Study officials:
name: Joao da Silva, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Subbiah V, Grilley-Olson JE, Combest AJ, Sharma N, Tran RH, Bobe I, Osada A, Takahashi K, Balkissoon J, Camp A, Masada A, Reitsma DJ, Bazhenova LA. Phase Ib/II Trial of NC-6004 (Nanoparticle Cisplatin) Plus Gemcitabine in Patients with Advanced Solid Tumors. Clin Cancer Res. 2018 Jan 1;24(1):43-51. doi: 10.1158/1078-0432.CCR-17-1114. Epub 2017 Oct 13.