Combination Therapy With NC-6004 and Gemcitabine in Advan... | NCT02240238

Label	Type	Description	Intervention Names
NC-6004 and Gemcitabine	Experimental		Drug: NC-6004 Drug: Gemcitabine

Name	Type	Description	Arm Group Labels	Other Names
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

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

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

Eligibility Module

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

Name	Affiliation	Role
Joao da Silva, MD		Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
California Cancer Associates for Research and Excellence		Encinitas	California	92024	United States

PubMed Identifier	Type	Citation	Retractions
29030354	Background	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.

ID	Title	Description
FG000	Phase 1 NC-6004 60 mg/m^2	Participants received intravenous (IV) infusion of NC-6004 60 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
FG001	Phase 1 NC-6004 75 mg/m^2

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 13, 2017	Aug 25, 2024

Arm/Group Information

ID	Title	Description
BG000	Phase 1 NC-6004 60 mg/m^2	Participants received intravenous (IV) infusion of NC-6004 60 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG001	Phase 1 NC-6004 75 mg/m^2	Participants received IV infusion of NC-6004 75 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG002	Phase 1 NC-6004 90 mg/m^2	Participants received IV infusion of NC-6004 90 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG003	Phase 1 NC-6004 105 mg/m^2	Participants received IV infusion of NC-6004 105 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG004	Phase 1 NC-6004 120 mg/m^2	Participants received IV infusion of NC-6004 120 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG005	Phase 1 NC-6004 135 mg/m^2	Participants received IV infusion of NC-6004 135 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG006	Phase 1 NC-6004 150 mg/m^2	Participants received IV infusion of NC-6004 150 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG007	Phase 1 NC-6004 165 mg/m^2	Participants received IV infusion of NC-6004 165 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG008	Phase 1 NC-6004 180 mg/m^2	Participants received IV infusion of NC-6004 180 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles until they experienced disease progression.
BG009	Phase 2 Cohort 1 (NSCLC)	Participants with non-small-cell lung cancer (NSCLC) received IV infusion of NC-6004 135 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles for up to 6 cycles.
BG010	Phase 2 Cohort 2 (Biliary Tract Cancer)	Participants with biliary tract cancer received IV infusion of NC-6004 135 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles for up to 8 cycles.
BG011	Phase 2 Cohort 3 (Bladder Cancer)	Participants with bladder cancer received IV infusion of NC-6004 135 mg/m^2 on Day 1 and gemcitabine 1250 mg/m^2 on Days 1 and 8 in 3-week treatment cycles for up to 6 cycles.
BG012	Total	Total of all reporting groups

Baseline Measures

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Age, Categorical