Combination Therapy With NC-6004 and Gemcitabine in Advanced Solid Tumors or Non-Small Cell Lung, Biliary and Bladder Cancer

Phase 1

Completed

Conditions: Solid Tumors

Interventions: Drug: NC-6004
Drug: Gemcitabine

Registration Number: NCT02240238

Lead Sponsor: NanoCarrier Co., Ltd.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 119

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NC-6004 and Gemcitabine	NC-6004	-
NC-6004 and Gemcitabine	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Determine the RPII Dose of NC-6004 in Combination With Gemcitabine	1 year	In the dose-escalation phase of the study (Part 1), to determine the dose-limiting toxicities (DLTs), MTD, and RPII dose of NC-6004 in combination with gemcitabine
Activity of NC-6004 Measured by Progression-free Survival (PFS)	1 year	In the expansion phase of the study (Part 2), to evaluate the activity of NC-6004 in combination with gemcitabine in patients with first-line Stage IV squamous NSCLC, first-line advanced or metastatic biliary tract cancer, and first-line metastatic or locally advanced bladder cancer compared with historical control as measured by local investigator/radiologist-assessed progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Name	Time	Method
ORR	Up to 40 weeks	To evaluate ORR, DCR (DCR = complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]), DOR, PFS, and OS
DCR	Up to 40 weeks	To evaluate ORR, DCR (DCR = complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]), DOR, PFS, and OS
DOR	every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.	To evaluate ORR, DCR (DCR = complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]), DOR, PFS, and OS
OS	every 6 weeks tumor assessments for response and disease progression after treatment discontinuation and telephone calls for survival every 12 weeks until disease progression.	To evaluate ORR, DCR (DCR = complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]), DOR, PFS, and OS
EORTC QLQ-C30	1 year	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) has the 5 functional scales (physical, role, emotional, cognitive, social), and 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). All of the scales and single item measures range in score from 0 to 100. A positive value of change from baseline means a better outcome in functional scales and a worse outcome in symptom scales.

Trial Locations

Locations (22): Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
University Hospitals Case Medical Center
🇺🇸
Cleveland, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Prof Dr I Chiricuta Institute of Oncology
🇷🇴
Cluj-Napoca, Romania
Coltea Clinical Hospital
🇷🇴
Bucharest, Romania
Oncology Center Sfantul Nectarie
🇷🇴
Craiova, Romania
Euroclinic Oncology Center SRL
🇷🇴
Iasi, Romania
Institutul Regional de Oncologie Iasi
🇷🇴
Iasi, Romania
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
Northwestern University Feinberg School of Medicine
🇺🇸
Chicago, Illinois, United States
Pacific Hematology Oncology Associates
🇺🇸
San Francisco, California, United States
Complex Oncology Center - Shumen EOOD
🇧🇬
Shumen, Bulgaria
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
🇮🇹
Meldola, Italy
Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
🇵🇱
Krakow, Poland
Med-Polonia Sp. z o.o.
🇵🇱
Poznan, Poland
Fundeni Clinical Institute
🇷🇴
Bucharest, Romania
Multiprofile Hospital for Active Treatment Serdika EOOD
🇧🇬
Sofia, Sofia-Grad, Bulgaria
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
🇮🇹
Milano, Italy
California Cancer Associates for Research and Excellence
🇺🇸
Encinitas, California, United States
University of North Carolina at Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States