Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Cancer

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

725 mg/m\^2 NUC-1031 administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle

1000 mg/m\^2 gemcitabine administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle

IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

NUC-1031

IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Jennifer Knox, MD

NuTide:121 compares NUC-1031 with gemcitabine, both in combination with cisplatin, in patients with previously untreated advanced biliary tract cancer.

The primary hypotheses are:

* The combination of NUC-1031 plus cisplatin prolongs overall survival compared to the gemcitabine plus cisplatin standard of care
* The combination of NUC-1031 plus cisplatin increases overall response rate compared to the gemcitabine plus cisplatin standard of care

1:1 randomization model to either Arm A or Arm B

Imaging scans will be assessed by blinded independent review according to RECIST v1.1

Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer

A Phase III Open-Label, Multi-Centre, Randomized Study Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Previously Untreated Locally Advanced or Metastatic Biliary Tract Cancer

Percentage of patients achieving a confirmed complete response (CR) or partial response (PR) to treatment as assessed by blinded independent review according to RECIST v1.1 criteria. ORR = patients with CR + patients with PR, where" CR = disappearance of all target lesions PR = at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters This outcome was assessed in the population of patients with measurable disease at baseline who were also randomized ≥28 weeks before the data cut-off (ITTMD28). Patients were to receive a confirmatory scan 28-42 days after response is first observed.

The median time, in months, from the date of randomization to the date of death from any cause. For patients who were alive at the time of a data cut-off or were permanently lost to follow up, duration of OS was censored at the date at which they were last known to be alive.

NuCana plc

All adverse events are reported for the Safety Population, which consisted of all patients in the ITT population who also received any study medication. This differs from all-cause mortality, which is reported for the ITT population.

725 mg/m\^2 NUC-1031 administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle

NUC-1031: IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

Cisplatin: IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

A - NUC-1031 and Cisplatin

1000 mg/m\^2 gemcitabine administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle

Gemcitabine: IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

Cisplatin: IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

B - Gemcitabine and Cisplatin

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Primary tumour location

Extent of disease

Patients with measurable disease as determined by RECIST v1.1 criteria:

Tumour lesions must be accurately measured in at least one dimension (longest diameter in the plane of measurement to be recorded) with a minimum size of:

* 10 mm by CT or MRI scan (CT/MRI scan slice thickness/interval no greater than 5 mm)
* 10-mm caliper measurement by clinical examination

To be considered pathologically enlarged and measurable, a lymph node must be ≥15 mm in the short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).

Measurable disease

The ECOG score describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The score runs from 0 to 5, with 0 denoting perfect health and 5 death. Patients with scores of 0 or 1 were eligible for this study:

0 - Asymptomatic. Fully active, able to carry on all predisease activities without restriction

1 - Symptomatic but completely ambulatory. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).

ECOG performance status

At Interim Analysis 1, the futility boundary for OS was crossed and the study was closed on 02 Mar 2022. Following study closure, data from the 05 April 2022 final data cut-off (30 day follow-up post the last patient last visit) were analysed. In general, the analyses performed on this final database were those that were scheduled to take place at Interim Analysis 2. However, any p-values or CIs obtained are only viewed as descriptive as the study was stopped for futility.

Medical and Scientific Affairs Department

Intent-to-treat with measurable disease at baseline randomized ≥28 weeks before the data cut-off (ITTMD28)

Spots Global Cancer Trial Database for distal bile duct