Investigation of gemcitabine combined with temsirolimus, in patients with inoperable or metastatic pancreatic cancer. A phase I-II study by the Hellenic Cooperative Oncology Group with biomarker evaluation (HE3/07)

Phase 1

• Conditions: Patients with inoperable or metastatic pancreatic cancer; Cancer - Pancreatic

• Registration Number: ACTRN12611000643976
• Lead Sponsor: Hellenic Cooperative Oncology Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-06-23
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

1.Provision of written informed consent
2. Age 18 years or older
3.Histologic proof of pancreatic cancer
4.Performance status between 50% and 100% on the Karnofsky scale
5.Life expectancy of greater than 12 weeks
6.Prior radiotherapy is allowed except for evaluable sites
7.Measurable or evaluable disease as according to Response Evaluation Criteria in Solid Tumors (RECIST)
8.All females of childbearing potential must have a negative serum or urine pregnancy test obtained within 2 days prior to initiation of treatment
9.White Blood Count >4000/microliter (mcl), platelets > 100,000/mcl and a hemoglobin level > 9.5 grams per deciliter (g/dl). Adequate baseline hepatic function, defined as a total bilirubin level < 2 miligrams per deciliter (mg/dl), serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) < 3 times the upper limits of normal, unless the liver is involved, in which case the transaminase levels could be up to five times the upper limits of normal. Creatinine < 1.5 mg/dl or creatinine clearance > 60 milliliter per minute (ml/min).
10Provision of adequate paraffin-embedded tumor tissue for translational studies and 10 milliliter (ml) peripheral blood for Deoxyribonucleic acid (DNA) study.

Exclusion Criteria

1.Patients with ampullary, periampullary, bile duct cancers or endocrine tumors of the pancreas
2.History of atrial or ventricular arrhythmias and/or history of congestive heart failure, even if medically controlled. History of clinical and electrocardiographically documented myocardial infarction within the last 6 months from study entry
3.Any evidence of clinically active interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
4.Pre-existing motor or sensory neurotoxicity grade 2 according to the World Health Organization (WHO) criteria (intolerable paresthesia and/or marked motor loss or worse)
5.History of previous chemotherapy
6.Symptomatic brain metastases
7.Known, severe hypersensitivity to temsirolimus or any of the excipients of this product
8.Other coexisting malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
9.Any unresolved chronic toxicity greater than Common Terminology Criteria (CTC) grade 2 from previous anticancer therapy
10. As judged by the investigator, any evidence of severe or uncontrolled systemic disease (eg unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
11.Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater or equal than 3 times the Upper Limit of the Reference Range (ULRR) if no demonstrable liver metastases or greater than 5 times the ULRR in the presence of liver metastases
12.Active infection or evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial/ receive protocol treatment
13.Pregnancy or breast feeding
14.Concomitant use of Cytochrome P450, family 3, subfamily A (Cyp3 A) inducers (phenytoin, carbamazepine, rifampicin, barbiturates or St John’s Wort) should be avoided and as should treatment wih strong CyP 3A inhibitors
15.Treatment with a non-approved or investigational drug within 30 days before Day 1 of trial treatment
16.Hypersensitivity to gemcitabine

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase I<br>Determine the feasibility and Maximum Tolerated Dose (MTD) for a combination of temsirolimus and gemcitabine. The proposed dose will be the dose of the previous level in which the MTD will be reached.[In the phase I of the study, 2-30 patients will be accrued. A minimum of 2 patients will be treated at the first dose levels. As per protocol design there is no -1 level and therefore, if two DLTs occur at the first two patients, trial has to be closed prematurely. Each dose level will include at least 3 subjects. <br>Once the MTD is reached and the proposed dose is defined, the study will move on to the phase II .];Phase II<br>6-month Progression Free Survival (PFS)[Response will be evaluated according to RECIST criteria. Tumor assessments will be performed by Computed Tomography (CT) in cylces 2, 4 and 7.]