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)

Objective Response Rate (ORR)

Overall Survival (OS)

Overall Study

Blood and Lymph Conditions

Leukemia

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28- day cycle

BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28-day cycle

BKM120

Novartis Pharmaceuticals

The purpose of this signal seeking study was is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

BKM120 for Patients With PI3K-activated Tumors

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 1 - BKM120 for Patients With PI3K-activated Tumors

Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at \>=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline

Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field "number of deaths resulting from adverse events" all those deaths resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Caucasian

Black

Asian

Other

Race/Ethnicity, Customized

Grade 0

Grade 1

Grade 2

ECOG Scoring: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=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, 2=Ambulatory and capable of all self-care but unable to carry out any work activities.

Up and about more than 50% of waking hours, 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, Cannot carry on any self-care. Totally confined to bed or chair, 5= Dead

ECOG Grade

PIK3CA gene mutation

PTEN gene mutation

PIK3CA amplification

PIK3R1 gene mutation

Protocol pre-defined gene mutation (by local labs)

Prior Lines of Antineoplastic Medications

Secondary objective: Duration of response was not analyzed due to low response rate observed

Study Director

Participant Clinical Benefit Response Rate

Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters

participants with an event

participants censored

Progression-Free Survival - Number of Participants With an Event

Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months

1 month

2 months

3 months

4 months

5 months

6 months

9 months

12 months

18 months

24 months

Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages

Overall Survival - Number of Participants With an Event

Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months

30 months

Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Pancreatic Neoplasms

Ovarian Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Gonadal Disorders

Pancreatic Cancer

Ovarian Cancer

Gemcitabine will be given at 1250 mg per meter squared over 2 hours days 1 and 8 of a 21 day cycle for a total of 4 cycles.

Radiation: External Radiation Therapy The total dose would be 19.2 Gy divided over 32 fractions twice a day, on day 1 and day 8 after chemotherapy.

Gemcitabine will be given at 1250 mg per meter squared over 2 hours days 1 and 8 of a 21 day cycle for a total of 4 cycles.

Radiation:External Radiation Therapy The total dose would be 19.2 Gy divided over 32 fractions twice a day, on day 1 and day 8 after chemotherapy.

\*\*Radiation is the experimental part of the study.

William Regine, MD

The purposes of this study are:

1. To assess the maximum tolerated dose of low-dose UART(Upper Abdominal Radiation Therapy ) or WART(Whole Abdominal Radiation Therapy) given in combination with standard fixed dose-rate Gemcitabine in patients with advanced gastrointestinal (GI) or ovarian tumors (Phase I).
2. To assess response rate and survival in advanced upper GI tumors following completion of therapy (Phase II).

Before entering this study the doctor will examine the patient and order blood tests. These tests will use approximately 10 ml of blood. Blood work should be done within 3 weeks prior to treatment.. Women of child-bearing potential are required to have a pregnancy test done within 7 days prior to the start of treatment . A CT or a PET/CT scan of the chest, abdomen and pelvis will be done within 4 weeks prior to starting treatment . All subjects participating in this study will receive radiation therapy and chemotherapy. Patients will get 4 cycles of chemotherapy along with radiation. Each cycle of chemotherapy consists of gemcitabine given i.v. on day 1 and day 8 of treatment. XRT is given on days 1 and 2 and on days 8 and 9 twice a day. This works out to 8 treatments of XRT per course of chemo. Overall, a total of 32 treatments of radiation therapy will be given during the 4 sessions of chemotherapy. Blood work for CBC with differential and platelets will be done prior to each dose of chemotherapy.The investigational portion of this study is the radiation therapy given to the abdomen on the same day and the day after the patient receives chemotherapy. Three-Four weeks after treatment completion the patient will be evaluated again. The treating physician will examine the patient and order blood tests. These tests will use approximately 10 ml of blood. The physician will also order a repeat CT or PET/CT to compare the disease status after treatment. These tests are not experimental and are part of routine check-ups of patients with pancreatic cancer. Patients will be followed for survival. Protected health information will not be reviewed by someone other than the patient's provider to identify potential subjects.

Low Dose Upper Abdominal Radiation Therapy (LD-UART) + Gemcitabine in Patients With Advanced, Unresectable Pancreatic Cancer (PC)

GCC 0319: Low Dose Upper Abdominal Radiation Therapy (LD-UART) + Gemcitabine in Patients With Advanced, Unresectable Pancreatic Cancer (PC)

Patients with distant mestastases to the liver

Locally advanced/recurrent disease without distant metastases.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Eli Lilly and Company

University of Maryland, Baltimore

Principal Investigator

Standard Chemotherapy, Gemcitabine With Concurrent Low Dose Ra

United States

Canada

Region of Enrollment

Nancy Kennedy

Use of LDFRT with systemic gemcitabine is safe, tolerable, and potentially effective. In advanced pancreatic cancer, where response rates with single agent gemcitabine have been low, this chemopotentiation paradigm may improve survival among a poor prognostic patient cohort.

Low Dose Fractionated Radiation Therapy (LDFRT) + Gemcitabine

Overall Response

Percentage of Participants With Distant Mestastases - Liver

Time of Advanced/Recurrent Disease Without Distant Metastases.

4 cycles (1 cycle = 21 days): Gemcitabine 1250/m2 given IV Day 1 and Day 8; with concurrent Low Dose Fractionated Radiation Therapy (LDFRT). The total Radiation dose would be 19.2 Gy divided over 32 fractions. Treatment will be given in 2 fractions with a minimum 4 hr inter-fraction interval, not to exceed 6 hours. Radiotherapy given after the initiation of Gemcitabine Days 1,2,8, and 9.

Gem(1250mg/m2, d1, 8) +LDFRT (60cGy/fx BID, d1,2,8,9)

Structured Responsive Exercise Training Programme (SRETP) prior to surgery

Structured Responsive Exercise Training Programme (SRETP) and psychological support prior to surgery

SRETP will involve short periods of exercise at a high intensity interspersed with short periods of exercise at a moderate intensity (aerobic interval training). We will also include resistance training in each session. Exercise intensities during the interval exercise-training program are specific to each patient and derived from CPET. Moderate intensity exercise is below the anaerobic threshold (AT). Patients will exercise at 80% of oxygen uptake (VO2) obtained at the anaerobic threshold (80%AT) for moderate intensity exercise - 3 minutes. Severe exercise intensity is recognised as 50% of the difference between the VO2 AT and VO2 Peak (50%∆) - 2 minutes.

SRETP

Support sessions will be patient-centred, giving the patient an opportunity to raise any issues/concerns they are having, this may include (but will not be limited to) ways of coping with their reactions to cancer, family and relationship issues, exploring personal issues and dealing with practical issues. Patients will have access to other resources available at the cancer centres including but not restricted to further information about their condition and how to access financial support. These processes reflect the best practice currently being delivered by cancer support centre staff in the Wessex region. Any patient deemed at risk (i.e. from suicidal ideation or self harm) will be reported to their GP, followed up by a letter.

Psychological support

Sandy Jack, PhD

Malcolm West, PhD

Samantha Leggett

Trial Phase: Phase III: A multi-centre efficacy pragmatic factorial design randomised controlled trial with patient informed development and process evaluation

Indication: Patients undergoing major electively resectable intra - cavity cancer surgery with or without neoadjuvant cancer treatments (including chemotherapy (NAC), chemoradiotherapy (CRT), or immunotherapy).

Objective: To investigate the efficacy of a community based Structured Responsive Exercise-training Programme (SRETP) ± psychological support on surgical outcome by reducing postoperative length of stay (LOS) and complications.

Secondary Objective:

To investigate the efficacy of a community based Structured Responsive Exercise-training Programme (SRETP) ± psychological support to improve disease-free overall survival. Cardiopulmonary Exercise test (CPET) variables, physical activity, morbidity, radiological markers of sarcopenia, toxicity, tumour down-staging, tumour regression, disability adjusted survival (WHODAS) overall survival and quality of life (QoL).

Rationale: Fitter patients have better surgical outcomes. Poor physical fitness measured objectively using cardiopulmonary exercise testing has been associated with increased LOS, increased morbidity and mortality in many patient cohorts undergoing major cancer surgery. Chemotherapy and radiotherapy have detrimental effects on physical fitness, which may in turn have a detrimental effect on the patients' ability to withstand surgery. Research suggests psychological factors including depression and self-efficacy (confidence to manage cancer-related problems) prior to surgery predict recovery trajectories in health-related quality of life up to 2 years after major surgery for colorectal cancer.

The aim is to investigate whether SRETP (Prehabilitation) ± psychological support prior to and during cancer treatment before major elective surgery reduces LOS, increases survival and improves their ability to self manage. Additionally, we aim to see if this intervention can bring about long-term behavioural change in relation to physical activity.

Trial Design: Phase III: A pragmatic factorial design randomised controlled to assess the effectiveness of a prehabilitation programme delivered prior to cancer treatments and/or major cancer surgery in patients undergoing elective intra-cavity major cancer surgery in Wessex.

Sample size: 1560

Intervention:

1. An in-hospital transition to a community based Structured Responsive Exercise-Training Programme (SRETP) ± psychological support (delivered in community/ council gyms or Cancer Support Centers). The intervention/s will be delivered before surgery. Patients receiving neoadjuvant cancer treatments prior to surgery will receive the intervention during and after these treatments.
2. Control: Standard care with extra monitoring

2x2 factorial design randomised controlled interventional trial

Masking of CPET assessors and dual reporting, masking of personnel involved in outcome data collection, masking of sarcopenia assessors

The Wessex Fit-4-Cancer Surgery Trial

A Pragmatic Factorial Design Randomised Controlled Study to Assess the Efficacy of the Implementation of a Prehabilitation Programme in Patients Undergoing Elective Major Intra - Cavity Cancer Surgery in Wessex

Date of hospital admission minus date of discharge would equal length of post-operative stay (LOS).

Change in cardiopulmonary exercise variables i.e. oxygen uptake (VO2) at anaerobic threshold (AT) and at peak exercise. A clinically significant difference in physical fitness is defined as ≥ 2ml/min/kg VO2 at AT.

Clinical or radiologically measured disease free survival

Patients post-operative morbidity survey (POMS) will be characterised on day 3, 5, 7 and 15. The POMS 18-item survey will be used to address nine domains of postoperative morbidity (pulmonary, infectious, renal, gastrointestinal, cardiovascular, neurological, wound complication, haematological and pain).

On day of discharge, patient's surgical complications (if any) will be graded using the Clavien-Dindo classification of surgical complications This classification is used to assess overall hospital morbidity following surgical procedures. Patients are graded as 0 (no complications) or Grade I-V based on the level of complication, including the number of organ system involvement. Grade V is defined as death of a patient. A record of the Comprehensive Complication Index (CCI) - an update of the Clavien-Dindo classification will also be collected

Number of steps while active using a triaxial accelerometer eg. Senseware

sleep efficiency using a triaxial accelerometer eg. Senseware

metabolic equivalents using a triaxial accelerometer eg. Senseware

Godin Leisure Time and Exercise questionnaire - A self-reported measure of physical activity

Changes in health related quality of life measurements using validated questionnaires; including:

EQ-5D-5L is a standardised measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. Applicable to a wide range of health conditions and treatments, it provides a simple descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care as well as in population health surveys

Changes in health related quality of life measurements using validated questionnaires; including:

Cancer specific quality of life will be measured using the EORTC-QLQ-C30.

Changes in health related quality of life measurements using validated semi-structured interview techniques

Self-efficacy (confidence) to self-manage chronic disease (SEMCD), measured using the Lorig SEMCD scale

A confidence scale that represents the patients confidence that a regular task can be achieved. 1 = Not confident at all and 10= totally confident.

Patients knowledge skills and confidence to manage their own health and care will be measured using the Patient Activation Measure (PAM)

Agreement or disagreement with statements. Choice between disagree strongly, disagree, agree, agree strongly and not applicable

Anxiety and depression will be measured using the Hospital Anxiety and Depression Scale (HADS)

A tick box questionnaire relating to anxieties and depression that a patient might have felt over the past week. Choices are most of the time, a lot fo the time, from time to time, and not at all for most questions.

Resilience, measured using the Connor-Davidson Resilience Scale (CD-RISC2)

Patients are asked to choose "x" in a box that best indicates how much they agree with the following statements resilience over the past month.

Options are not at all true; rarely true; sometimes true; often true; true nearly all of the time

Brief illness perception questionnaire (B-IPQ) - A self- reported nine-item scale designed to rapidly assess the cognitive and emotional representations of illness by a questionnaire.

Various illness questions are asked and the patient picks a number from 0 to 10; 0= no affect at all and 10= severely affects my life.

Medical research council (MRC) RE-AIM reporting

CT, MRI, PET CT full report from radiologist including TNM stage, venous invasion, resection margin involvement, tumour metabolic activity, RECIST staging and any other cancer pathway specific staging/restaging test. Raw DICOM files from radiological softwares or via the PACS team will be downloaded securely to measure radiological markers of sarco-cachexia.

Neoadjuvant cancer therapy induced toxicity measured using the CTC AE v4

Radiology - CT, MRI, PET CT - Tumour Node Metastasis (TNM v7) stage

Radiology - CT, MRI, PET CT full report from radiologist mainly including venous invasion

Radiology - CT, MRI, PET CT full report from radiologist mainly including resection margin involvement

Radiology - CT, MRI, PET CT full report from radiologist mainly including tumour metabolic activity

Radiology - CT, MRI, PET CT full report from radiologist mainly including RECIST staging

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer	NCT04163900	Biliary Tract C...	NUC-1031 Gemcitabine Cisplatin	18 Years -	NuCana plc
BKM120 for Patients With PI3K-activated Tumors	NCT01833169	PI3K Pathway Ac...	BKM120	18 Years - 100 Years	Novartis
Low Dose Upper Abdominal Radiation Therapy (LD-UART) + Gemcitabine in Patients With Advanced, Unresectable Pancreatic Cancer (PC)	NCT00390182	Gastrointestina... Ovarian Neoplas...	Gemcitabine	18 Years -	University of Maryland, Baltimore
The Wessex Fit-4-Cancer Surgery Trial	NCT03509428	Cancer	SRETP Psychological s...	18 Years -	University Hospital Southampton NHS Foundation Trust

Spots Global Cancer Trial Database for hepatobiliary