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

NCT02240238 | Completed Phase 1 Results FDA Drug

• 1 other identifier: NC-6004-004A
• Study Type: interventional
• Target: 119
• Locations: 5 countries
• Sites: 22

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• ORR

  Up to 40 weeks

• DCR

  Up to 40 weeks

• 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.

• 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

  1 year

Study Arms (1)

NC-6004 and Gemcitabine

EXPERIMENTAL

Drug: NC-6004; Drug: Gemcitabine

Interventions

NC-6004 DRUG

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.

NC-6004 and Gemcitabine

Gemcitabine DRUG

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.

NC-6004 and Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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

You may not qualify if:

• 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

Sponsors & Collaborators

• NanoCarrier Co., Ltd.: lead

Study Sites (22)

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

Pacific Hematology Oncology Associates

San Francisco, California, 94115, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44121, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Multiprofile Hospital for Active Treatment Serdika EOOD

Sofia, Sofia-Grad, 1632, Bulgaria

Location

Complex Oncology Center - Shumen EOOD

Shumen, 9700, Bulgaria

Location

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST

Meldola, 47014, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda

Milan, 20162, Italy

Location

Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie

Krakow, 31826, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60693, Poland

Location

Fundeni Clinical Institute

Bucharest, 22328, Romania

Location

Coltea Clinical Hospital

Bucharest, 30171, Romania

Location

Prof Dr I Chiricuta Institute of Oncology

Cluj-Napoca, 400015, Romania

Location

Oncology Center Sfantul Nectarie

Craiova, 200347, Romania

Location

Euroclinic Oncology Center SRL

Iași, 700106, Romania

Location

Institutul Regional de Oncologie Iasi

Iași, 700483, Romania

Location

Related Publications (1)

• 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.

  PMID: 29030354 BACKGROUND

MeSH Terms

Interventions

demplatin pegraglumer; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: NANO MRNA Clinical Info Admin
• Organization: NANO MRNA Co.,Ltd.

clinical.info@nanomrna.co.jp

+81 (0)3-6432-4792

Study Officials

• Joao da Silva, MD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2014
• First Posted: September 15, 2014
• Study Start: May 1, 2014
• Primary Completion: May 6, 2019
• Study Completion: May 6, 2019
• Last Updated: January 22, 2025
• Results First Posted: January 22, 2025

Record last verified: 2025-01

Locations

PL (2); US (10); RO (6); BU (2); IT (2)