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

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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: NC-6004; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Shumen, Bulgaria, 9700
    • Complex Oncology Center - Shumen EOOD
  • Sofia-Grad
    • Sofia, Sofia-Grad, Bulgaria, 1632
      • Multiprofile Hospital for Active Treatment Serdika EOOD
• Italy
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
• Poland
  • Krakow, Poland, 31826
    • Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
  • Poznan, Poland, 60693
    • Med-Polonia Sp. z o.o.
• Romania
  • Bucharest, Romania, 22328
    • Fundeni Clinical Institute
  • Bucharest, Romania, 30171
    • Coltea Clinical Hospital
  • Cluj-Napoca, Romania, 400015
    • Prof Dr I Chiricuta Institute of Oncology
  • Craiova, Romania, 200347
    • Oncology Center Sfantul Nectarie
  • Iasi, Romania, 700483
    • Institutul Regional de Oncologie Iasi
  • Iasi, Romania, 700106
    • Euroclinic Oncology Center SRL
• United States
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence
    • La Jolla, California, United States, 92037
      • UC San Diego Moores Cancer Center
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • University Hospitals Case Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NC-6004 and Gemcitabine	Drug: NC-6004; NC-6004 - given at escalating doses of 60, 75, 90, 105, 120, 135, 150, 165, or 180 mg/m2 according to observations of dose-limiting toxicity.; Drug: Gemcitabine; Gemcitabine 1250 mg/m2 will be administered as a 30 minute intravenous infusion on Day 1 after the completion of the NC 6004 infusion and on Day 8 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the RPII Dose of NC-6004 in Combination With Gemcitabine	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	1 year
Activity of NC-6004 Measured by Progression-free Survival (PFS)	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and OS	Up to 40 weeks
DCR	To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and OS	Up to 40 weeks
DOR	To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and 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.
OS	To evaluate ORR, DCR (DCR = complete response [CR] + partial response [PR] + stable disease [SD]), DOR, PFS, and 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.
EORTC QLQ-C30	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.	1 year

Collaborators and Investigators

• Sponsor: NanoCarrier Co., Ltd.
• Investigators: Principal Investigator: Joao da Silva, MD

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): May 6, 2019
• Study Completion (Actual): May 6, 2019

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimated): September 15, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: NC-6004-004A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No