Phase II study evaluating the efficacy of Pasireotide long-acting release (LAR; SOM230) dose escalation in patients with refractory non-functional gastroenteropancreatic neuroendocrine tumors (GEP NETs).

Phase 2

• Conditions: Gastro-entero-pancreatic neuroendocrine tumours; Cancer - Neuroendocrine tumour (NET)

• Registration Number: ACTRN12615001328561
• Lead Sponsor: Peter MacCallum Cancer Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-12-04
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Male or female, over 18 years
2. Patients with an histologically documented diagnosis of non-functional WDNET, defined according to the last WHO classification criteria for NET of gastro-entero-pancreatic (WHO/ENET 2010), bronchial and thymic origin (WHO 2004)
2. Radiologic disease progression after at least 3 months of octreotide LAR 30mg/28 days
3. Measurable/evaluable disease per RECIST Version 1.1,1 (as determined by relevant imaging based on disease site (i.e. for example by multiphase MRI or triphasic CT scan for hepatic metastasis)
4. ECOG PS 0-2
5. Adequate organ function:
Bone marrow: Platelets greater than or equal to 100x10^9/L, Neutrophils greater than or equal to 1.5x10^9/L, Hb greater than or equal to 9g/L
Liver: Bilirubin less than or equal to 2.0 xUNL, INR less than or equal to 1.3, AST/ALT less than or equal to 2.5 xUNL (if no hepatic metastases) or AST/ALT less than or equal to 5.0 x UNL (if hepatic metastases).
Renal: Serum creatinine less than or equal to 2.0 X ULN
6. Females of childbearing potential must provide a negative pregnancy test at the start of the study. Female patients who are at risk of becoming pregnant must agree to use an effective method of contraception. Female patients must agree to use 2 medically acceptable methods of contraception, 1 being an oral contraceptive, dermal patch, or progestin (implantation or injection), and the other being a medically acceptable barrier method; alternatively, 2 medically acceptable barrier methods may be used. Medically acceptable barrier methods of contraception that may be used by the participant and/or his/her partner include: abstinence; diaphragm with spermicide; intrauterine device (IUD); condom together with foam, spermicide, or vaginal spermicidal suppository. Prohibited methods include the rhythm method, withdrawal, condoms alone, or diaphragm alone
7. Male patients must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception as described above.
8. Informed and written consent as per the Participant Information and Consent Form
9. Compliance with trial therapy or trial-related investigations/evaluations by the patient

Exclusion Criteria

1. Patients with intermediate (Grade 2) or high grade (grade 3) NET
2. SSA Naive patients
3. Patients that have undergone surgery related to NET within 4 weeks prior to study entry or has surgery planned during the study
4. Patients that have previously received any specific anti-tumour treatment such as chemotherapy (within the previous 4 weeks), (chemo) embolisation (within the previous 3 months), radiotherapy (within the previous 4 weeks) or interferon (within the previous 4 weeks) or PRRT within the last 6 months.
5. Patients that have had a previous cancer (except basal cell carcinoma of the skin, in situ carcinoma of the cervix/uterus, thyroid microcarcinoma, or eradicated thyroid or prostate cancers). Patients with a history of cancer that was not the above mentioned case can be included if they have been treated with curative intent and have been free from disease for more than 3 years.
6. Diabetic patients with poor glycemic control as evidenced by HbA1c >8%
7. Patients with risk factors for torsades de pointes, i.e. patients with a baseline QTcF >450 ms in males, and >460ms in females. Or patients with uncontrolled (despite supplementation) hypokalemia or hypomagnesaemia, uncontrolled hypothyroidism, family history of long QT syndrome, or concomitant medications known to prolong QT interval
8. Patients with clinically significant valvular disease
9. Patients with symptomatic cholelithiasis
10. Patients who have congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, advanced heart block, history of acute myocardial infarction less than one year prior to study entry or clinically significant impairment in cardiovascular function
11. Patients with liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis, or patients with ALT/AST > 2.5 X ULN, serum bilirubin > 2.0 X ULN, in the absence of liver metastases
12. Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving pasireotide
13. Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
14. Patients with the presence of active or suspected acute or chronic uncontrolled infection
15. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study
16. Pregnant or lactating women
17. At the time of inclusion, on-going AE considered to be related to the treatment with SSA with a severity higher than grade 1
18. Patients on lower doses than octreotide LAR 30mg every 28 days.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To estimate the antiproliferative effect of dose escalated pasireotide LAR in patients who have radiologically progressed on octreotide 30mg/q28d on progression-free survival at 96 weeks from start of treatment.<br><br>This endpoint will be assessed by progression free survival at 96 weeks from time of commencement of pasireotide 40mg LAR therapy until date of radiological progression (via CT.MRI) at the maximum dose of pasireotide LAR as evaluated by RECIST 1.1 criteria. <br><br>A radiological primary endpoint is appropriate given that the study is endeavouring to evaluate the antiproliferative effects of dose escalation.[PFS at 96 weeks from time of commencement of pasireotide 40mg LAR therapy.]