CAP7.1 for the Treatment of Advanced Stage, Therapy Refractory Lung and Biliary Tract Tumors

Study Overview
=================
Brief Summary
-----------------
To assess the anti-tumor activity of CAP7.1 based on the observed objective response rate and rate of disease stabilization, as defined by the below primary and secondary endpoints, in patients with Non-Small Cell Lung Carcinoma (NSCLC), SCLC or biliary cancer who have progressed despite one or more previous chemotherapy line.

Detailed Description
-----------------
A phase II evaluation will be performed in adult patients in parallel studies in 3 tumor types: NSCLC, SCLC and Biliary Tract Cancer. All patients will have advanced or metastatic disease with primary or secondary resistance to standard therapy. In each tumor type the patients will be randomized to receive either therapy with CAP7.1 or best supportive care according to institution standards. Patient in the Control group who progress may cross over to CAP7.1, however these patients will be analyzed separately from the patients randomized to CAP7.1.

Official Title
-----------------
Phase II Trial of CAP7.1 in Adult Patients With Refractory Malignancies: Small Cell Lung Carcinoma, Non-Small Cell Lung Carcinoma, Biliary Carcinoma (PIITCAP)

Conditions
-----------------
Advanced Endstage Solid Carcinomas in Adults

Intervention / Treatment
-----------------
* Drug: CAP7.1


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically- or cytologically-confirmed, advanced disease with documented progression (RECIST1.1.) after one or several chemotherapy line Patients may also have received molecular targeted therapy and progressed while on therapy or after completion Must have recovered from the acute reversible effects of previous anti-cancer chemotherapy, usually 3-4 weeks after myelosuppressive chemotherapy Exclusion Criteria: Serious concurrent medical condition, which could affect compliance with the protocol or interpretation of results. Patients with uncontrolled infection and patients known to be infected with the human immunodeficiency virus (HIV) or hepatitis infection are not eligible for the study Pregnancy or breast-feeding
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Small cell lung cancer<br>Histologically- or cytologically-confirmed, limited and extensive SCLC disease with progression after first or second line treatment | Drug: CAP7.1<br>* CAP7.1 is a prodrug of Etoposide released after via specific carboxyesterase<br>|
| Experimental: Non small cell lung cancer<br>Histologically- or cytologically-confirmed diagnosis of NSCLC with Stage IIIB or IV after failure of at least two lines of therapy | Drug: CAP7.1<br>* CAP7.1 is a prodrug of Etoposide released after via specific carboxyesterase<br>|
| Experimental: biliary tract cancer<br>Histologically or cytologically confirmed diagnosis of biliary tract cancer progress after first line therapy | Drug: CAP7.1<br>* CAP7.1 is a prodrug of Etoposide released after via specific carboxyesterase<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression | Assessment of antitumor activity based on RECIST 1.1 criteria (complete response; partial response; stable disease) | 18 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Percentage of Subjects With Objective Response [i.e., complete response (CR) + partial response (PR)] According to RECIST1.1 |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Time to Treatment Failure |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Progression-Free Survival (PFS) |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Disease-free survival |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Overall Survival (OS) |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Maximum Observed Drug Concentration (Cmax) of CAP7.1 in Plasma |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Time to Reach Maximum Drug Concentration (tmax) of CAP7.1 in Plasma |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Half-life Associated With the Terminal Slope (t1/2) of CAP7.1 in Plasma |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 
| Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC) of CAP7.1 in Plasma |  | Start of study treatment until 26 days post-last study treatment (approximately 4 years and 2 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
therapy refractory, solid tumours, endstage