Trabectedin in Treating Patients With Metastatic Pancreatic Cancer After First-Line Chemotherapy (PACT-18)

Salvage Therapy With Trabectedin in Metastatic Pancreatic Adenocarcinoma: A Single-Arm Phase II Trial

RATIONALE: Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well trabectedin works in treating patients with metastatic pancreatic cancer after first-line chemotherapy.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: trabectedin; Drug: trabectedin

Detailed Description

OBJECTIVES:

Primary

• To assess the therapeutic activity of trabectedin, in terms of progression-free survival (PFS) rate at 6 months, in patients with metastatic pancreatic adenocarcinoma progressed after gemcitabine-containing first-line chemotherapy.

Secondary

• To assess the safety profile of this drug.
• To assess the response rate and response duration.
• To assess the overall survival of these patients.
• To assess the PFS rate at 9 and 18 weeks.
• To perform blood, plasma, and tumor tissue sampling for biological studies, in order to identify biomarkers predictive for resistance or sensitivity to trabectedin, and to characterize the impact of pharmacogenomic and pharmacokinetic profile on anti-tumor activity in translational research studies.

OUTLINE: Patients receive trabectedin IV over 3 hours on day 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Blood samples and tumor tissue are analyzed for identifying biological markers predictive for resistance to treatment and pharmacogenomic and pharmacokinetic profiling on anti-tumor activity in translational research studies.

After completion of study treatment, patients are followed up periodically.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Istituto Scientifico H. San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the pancreas

• Metastatic disease progressed after 1 prior gemcitabine-contained chemotherapy

  • May be given with neoadjuvant, adjuvant, or palliative therapy
• Measurable disease according to RECIST criteria
• No symptomatic brain metastasis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Bone marrow, liver, and kidney function normal
• Not pregnant or nursing
• Fertile patients must use effective contraception

• No severe comorbidities, including any of the following:

  • Cardiac disease
  • History of psychiatric disability
• No other prior or concurrent malignancy except surgically cured carcinoma in-situ of the cervix, basal cell or squamous cell carcinoma of the skin, and other neoplasms without evidence of disease for ≥ 5 years
• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior second-line chemotherapy
• No other concurrent chemotherapy or target therapy
• No concurrent treatment with other experimental drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: trabectedin; 1.3 mg/mq as a 3 hour continuous infusion every three weeks until progression	Drug: trabectedin; 1.3 mg/mq as a 3 hour continuous infusion every three weeks; Other Names: YONDELIS; Drug: trabectedin; 1.3 mg/mq as a 3 hour continuous infusion every three weeks until progression; Other Names: ET 743

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) rate at 6 months	CT scan	every 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile	outpatient visit, laboratory findings	every 3 weeks
Response rate and response duration	CT scan	every 2 months
Overall survival	outpatient visit, phone interview	every 3 weeks during therapy, every 2-3 months thereafter
PFS rate at 9 and 18 weeks	CT scan	every 9 weeks
Identify biomarkers predictive for resistance or sensitivity to trabectedin	tissue, blood, serum collection	at trial start
Impact of pharmacogenomic and pharmacokinetic profile on anti-tumor activity	blood samples	based on a pre-definid sample collection schedule

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 20, 2011
• First Submitted That Met QC Criteria: April 20, 2011
• First Posted (Estimate): April 21, 2011

Study Record Updates

• Last Update Posted (Estimate): August 11, 2014
• Last Update Submitted That Met QC Criteria: August 8, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Trabectedin
• Other Study ID Numbers: CDR0000698981; PACT-18 (Other Identifier: IRCCS San Raffaele); 2010-024287-17 (EudraCT Number)