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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Endstage Solid Carcinomas in Adults
• Intervention / Treatment: Drug: CAP7.1

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

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	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)

Collaborators and Investigators

• Sponsor: CellAct Pharma GmbH
• Collaborators: Mundipharma-EDO GmbH

Publications and helpful links

General Publications

• Keilholz U, Rohde L, Mehlitz P, Knoedler M, Schmittel A, Kummerlen V, Klinghammer K, Treasure P, Lassus M, Steventon G, Machacek M, Utku N. First-in-man dose escalation and pharmacokinetic study of CAP7.1, a novel prodrug of etoposide, in adults with refractory solid tumours. Eur J Cancer. 2017 Jul;80:14-25. doi: 10.1016/j.ejca.2017.03.032. Epub 2017 May 19.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 8, 2011
• Primary Completion (ACTUAL): September 8, 2015
• Study Completion (ACTUAL): April 10, 2017

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (ESTIMATE): March 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2018
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: solid tumours; therapy refractory; endstage
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma
• Other Study ID Numbers: CPN710102; 2012-002378-30 (EUDRACT_NUMBER)