Combination of antiangiogenic therapy using the mTOR-inhibitor RAD001 and low dose chemotherapy for locally advanced and/or metastatic pancreatic cancer – a dose finding study

• Conditions: advanced and/or metastatic pancreatic cancer; MedDRA version: 9.1Level: LLTClassification code 10033605Term: Pancreatic cancer metastatic

• Registration Number: EUCTR2006-003403-39-DE
• Lead Sponsor: ovartis Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03-06
• Last Update Posted: 21 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Histological confirmed locally advanced, irresectable pancreatic adenocarcinoma (head, corpus, tail) with or without distant metastases
2. compliant patient, regular follow-up possible
3. Adequate bone marrow, liver and renal function on RAD001 treatment, as shown by:
WBC equal or higher than 3 x 109/L
Absolute neutrophil count (ANC) equal or higher than 1.5 x 109/L
Hemoglobin equal or higher than 9 g/dL
Platelet count equal or higher than 100 x 109/L
Serum transaminase activity (AST/SGOT & ALT/SGPT) < 2.5 X ULN oder 3 x ULN with the exception of serum transaminases (< 5 x ULN) if the patient has liver metastases
Serum total bilirubin < 2.5 x ULN
Serum creatinine < 1.5 x ULN or a creatinine clearance of equal or higher than 60 mL/min.
4. At least one measurable lesion (longest diameter equal or higher than 20 mm on conventional CT or MRI scan; equal or higher than 10 mm on spiral CT) according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. The scans should be approximately 2 weeks old to be used as baseline scan.
5. Patients must be at least 4 weeks since prior major surgery and recovered, at least 2 weeks and recovered since prior minor surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
6. ECOG Performance Status 0-2 (Post Text Supplement 2)
7. Age = 18 years
8. Signed informed consent must be obtained prior to any screening procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Women who are pregnant or breast feeding, or women able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study
2. Documented intolerance or history of allergy to RAD001 or Gemcitabine
3. Patients with a history of another malignancy within 5 years prior to study entry, except curatively treated non-melanotic skin cancer or in-situ cervical cancer
4. Patients with any concurrent major medical condition liable to compromise the patient's participation in the study (e.g. known HIV infection, uncontrolled diabetes, chronic or acute renal or liver disease, uncontrolled infections including abscess or fistulae, fibrosis of the lung serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV (Post Text Supplement 4))
5. Use of other investigational cancer therapies within 28 days prior to enrollment or which are currently being or planned to be received during the course of the study
6. Patients presenting with known or symptomatic CNS metastases or leptomeningeal involvement
7. Chronic treatment with systemic steroids or another immunosuppressive agent
8. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
9. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin). Quick-value < 50 % or PTT more than 1,5 fold higher
10. Patients who have received prior treatment with an mTor inhibitor
11. Patients who have received a prior treatment with Gemcitabine. Only adjuvant treatment with Gemcitabine is allowed. Interval between treatment and relapse should be 3 months minimum
12. History of noncompliance to medical regimens
13. Patients unwilling to or unable to comply with the protocol
14. Patients committed to an institution by order of the authorities or court decision

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of Gemcitabine in combination with Everolimus.;Secondary Objective: To characterize the safety and tolerability of Everolimus in combination with Gemcitabine including acute and chronic toxicities, in these patient populations.<br>To characterize the single-dose and repeated-dose pharmacokinetic assessments of Everolimus and Gemcitabine combination therapy in these patient populations.<br>At MTD dose level expansion: To evaluate preliminary efficacy (objective response rates [ORR], duration of response, progression-free survival [PFS] at 24 weeks, and overall survival [OS]) in these patient populations (in phase II).<br>;Primary end point(s): To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of Gemcitabine in combination with Everolimus.