An open label, stratified, single-arm phase II study of RAD001 in patients with advanced pancreatic neuroendocrine tumor (NET) after failure of cytotoxic chemotherapy - NA

• Conditions: Pancreatic neuroendocrine tumors (NET) comprise only 1-2% of all pancreatic tumors. The annual incidence is approx. 3.5 to 4 per million population. The hormones secreted by pancreatic NET depend upon the cell of origin and are physiologically involved in a network of autocrine, paracrine, endocrine and neurotransmitter communication. While hormone secretion is not observed in all cases, the nonfunctioning” pancreatic NET tend to be more aggressive and present with symptoms of tumor bulk.

• Registration Number: EUCTR2006-001247-64-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-23
• Last Update Posted: 22 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

Inclusion criteria for both strata:
1. Adult male or female patients (=18 years of age).
2. Advanced (unresectable or metastatic) biopsy-proven pancreatic NET documented as follows:
• Radiologic, operative, or pathology reports should document a pancreatic location of tumor at some point in the patient’s history;
• Patients must have confirmed low-grade or intermediate-grade neuroendocrine carcinoma. Pathology report should state one of the following: carcinoid, islet cell carcinoma, pancreatic endocrine tumor, low-grade or well-differentiated neuroendocrine carcinoma, atypical carcinoid, intermediate-grade or moderately differentiated neuroendocrine carcinoma;
• Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, goblet cell carcinoid and small cell carcinoma are not eligible.
3. Documented objective progression of disease by RECIST criteria while receiving cytotoxic chemotherapy or documented progression at any time after receiving an adequate course of cytotoxic chemotherapy (i.e., at least 3 consecutive cycles or months of treatment with the same cytotoxic drug or regimen). Previous therapy with alpha interferon or tyrosine kinase inhibitors are allowed but would not be considered to be prior chemotherapy.
Objective progression of disease must be documented by RECIST criteria. Any of the following would be sufficient according to RECIST:
• a 20% increase in the sum of unidimensionally measured target lesions;
• a new lesion;
• unequivocal increase in non-measurable disease.
4. At screening, a triphasic CT or MRI scan must demonstrate measurable disease by RECIST criteria, i.e., the presence of at least one measurable lesion. Measurable disease lesions must be accurately measured in at least one dimension with longest diameter = 20 mm using conventional techniques or = 10 mm with spiral CT scan (with minimum lesion size no less than double the slice thickness)
5. Adequate bone marrow function as shown by: ANC = 1.5 x 109/L, Platelets = 100 x 109/L, Hb >9 g/dL.
6. Adequate liver function as shown by:
• serum bilirubin = 1.5 x ULN;
• INR < 1.3 (or < 3 on anticoagulants);
• ALT and AST = 2.5x ULN ( = 5x ULN in patients with liver metastases).
7. Adequate renal function: serum creatinine = 1.5 x ULN.
8. Fasting serum cholesterol =300 mg/dL OR =7.75 mmol/L AND fasting triglycerides = 2.5 x ULN. NOTE: In cases where one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication, see Section 6.3.4.3.
9. Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or a urine pregnancy test 48 hours prior to the administration of the first study treatment.
10. WHO Performance Status 0-2.
11. Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.
Inclusion criteria for Stratum 2 only:
1. Meet all inclusion criteria defined above for both strata.
2. Receiving treatment (at least 3 consecutive months) with Sandostatin LAR® Depot.
3. In addition to documentation of progressive disease on or after chemotherapy, patients in stratum 2 must have documented objective progression of disease while receiving Sandostatin LAR® Depot. The initial and follow-up scans documenting progression mu

Exclusion Criteria

1. Anticancer therapy within 3 weeks of enrollment including chemotherapy, hormonal therapy, immunotherapy, surgery or radiotherapy. Investigational agents used solely for imaging purposes are permissible if deemed safe and acceptable by local review authorities. Sandostatin LAR® Depot is allowed in stratum 2.
2. Hepatic artery embolization within the last 6 months (1 month if there are other sites of measurable disease), or cryoablation of hepatic metastasis within 2 months of enrollment.
3. Prior therapy with RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus).
4. Patients with uncontrolled diabetes mellitus as defined by fast blood sugar > 1.5 x ULN.
5. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
6. Patients with severely impaired lung function.
7. Patients with acute or chronic, active infectious disorders or patients with nonmalignant medical illnesses that are uncontrolled, or whose control may be jeopardized by the complications RAD001 initiation.
8. No other prior or concurrent malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
9. Known history of immunocompromise, including a positive HIV test. An HIV test will not be required; however, previous medical history will be reviewed.
10. Female patients who are pregnant or nursing (lactating), or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes.
11. Concomitant medications known to inhibit, induce or be a substrate to isoenzyme CYP3A are excluded unless the drugs are medically necessary and no substitutes are available. If there are no acceptable substitutes, special precautions should be taken in these patients.
Additional Exclusion Criteria for Stratum 1 only:
1. Received treatment with Sandostatin LAR® Depot or any other long-acting somatostatin analogue in the 60 days prior to enrollment or any short-acting somatostatin analogue in the two weeks prior to enrollment.

Study & Design

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