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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02240238
• Other study ID #: NC-6004-004A
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2014
• Est. completion date: May 6, 2019

Study information

• Verified date: February 2020
• Source: NanoCarrier Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: May 6, 2019
• Est. primary completion date: May 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumors
• Urinary Bladder Neoplasms

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
NanoCarrier Co., Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Italy,  Poland,  Romania, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall response rate	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.
Secondary	Therapy-related AEs	Incidence and severity of therapy-related AEs	1 year
Secondary	EORTC QLQ-C30	To evaluate QoL using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	1 year
Secondary	Safety and tolerability as measured by severity of AEs and laboratory abnormalities	The safety endpoints for this study are the incidence and severity of AEs and laboratory abnormalities, according to the NCI CTCAE version 4.03, the occurrence of SAEs and treatment discontinuations due to AEs, and nausea severity and vomiting incidence obtained from the patient diary	1 year