Overview

This trial is active, not recruiting.

Condition well-differentiated non-pancreatic neuroendocrine carcinoma
Treatments axitinib, sandostatin lar, placebo
Phase phase 2
Targets VEGF, PDGF
Sponsor Grupo Espanol de Tumores Neuroendocrinos
Start date November 2011
End date July 2015
Trial size 80 participants
Trial identifier NCT01744249, 2011-001550-29, AXI-IIG-02

Summary

The purpose of this study is to determine if Axitinib prolongs progression-free survival of patients with advanced well differentiated neuroendocrine carcinomas of non-pancreatic origin compared to placebo.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Axitinib 5 mg BID + Sandostatin LAR 30mg/28 days
axitinib
Orally, 5mg, twice daily, until progression or until unacceptable toxicity, with or without food intake.
sandostatin lar
Intramuscular, 30mg, single injection every 28 days, until disease progression or unacceptable toxicity
(Placebo Comparator)
Placebo BID + Sandostatin LAR 30mg/28 days
sandostatin lar
Intramuscular, 30mg, single injection every 28 days, until disease progression or unacceptable toxicity
placebo
orally, twice daily, until disease progression or unacceptable toxicity, with or without food intake.

Primary Outcomes

Measure
Progression Free Survival
time frame: until disease progression, end of treatment or minimum 6 months

Secondary Outcomes

Measure
Objective response rate (RECIST criteria) and duration of response
time frame: Until disease progression, end of treatment or minimum 6 months
Biochemical response (5-OH-Indolacetic acid and chromogranin A)
time frame: Until disease progression, end of treatment or minimum 6 months
Overall survival
time frame: Until death, last follow-up, or minimum 6 months
Safety profile
time frame: Until disease progression, end of treatment or minimum 6 months
Biomarkers
time frame: Until disease progression or after 6 months of treatment

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histologically confirmed well or moderately differentiated neuroendocrine carcinoma (grade I and II WHO 2010)of non-pancreatic origin 2. Ki-67<20% 3. Metastatic or locally advanced disease (clinically or radiologically confirmed) not amenable to treatment with curative intent 4. Progressive disease documented in the prior 12 months (RECIST criteria) 5. Measurable disease 6. Prior treatment with somatostatin analogues permitted 7. Prior interferon therapy allowed 8. One prior systemic chemotherapy allowed 9. No prior VEGF- or VEGFR-targeted therapy allowed 10. Adequate organ function as defined by the following criteria: - absolute neutrophil count (ANC) ≥1500 cells/mm3; - platelets ≥75,000 cells/mm3; - hemoglobin ≥9.0 g/dL; - AST and ALT ≤2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT ≤5.0 x ULN; - total bilirubin ≤1.5 x ULN; - serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min; - urinary protein <2+ by urine dipstick. If dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours. 11. Male or female, age ≥18 years. 12. ECOG performance status of 0-2. 13. Life expectancy of ≥12 weeks. 14. At least 4 weeks since the end of prior systemic treatment, radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 3.0 grade ≤1 or back to baseline except for alopecia or hypothyroidism. 15. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤150 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible. 16. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment. 17. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. 18. Willingness and ability to comply with scheduled visits, treatment plans and study procedures. Exclusion Criteria: 1. The following endocrine tumor types may not be included: paraganglioma, adrenal, thyroid, parathyroid or pituitary endocrine tumors. 2. Major surgery in <4 weeks or radiation therapy <2 weeks prior to starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated. 3. Gastrointestinal abnormalities including: - inability to take oral medication; - requirement for intravenous alimentation; - prior surgical procedures affecting absorption including total gastric resection; - treatment for active peptic ulcer disease in the past 6 months; - active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; - malabsorption syndromes. 4. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)unless they can be substituted with a different medication with minimal inhibition of CYP3A4/5. The coadministration could reduce the plasmatic concentration of axitinib. 5. Current use or anticipated need for treatment with drugs that are known CYP3A4/5 inducers (ie, carbamazepine, dexamethasone, felbamate, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St.John's wort)unless they can be substituted with a different medication with minimal inhibition of CYP3A4. The coadministration could reduce the plasmatic concentration of axitinib. 6. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed. 7. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 8. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment. 9. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism. 10. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. 11. History of a malignancy (other than renal cell cancer) except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 5 years. 12. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. 13. Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 6 months after discontinuing study treatment The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate. 14. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Additional Information

Official title Phase II Randomized Double-blind Study of Sandostatin LAR in Combination With Axitinib Versus Placebo in Patients With Progressive Advanced Well-differentiated Neuroendocrine Carcinomas of Non-pancreatic Origin
Principal investigator Luis Antón Aparicio, MD
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Grupo Espanol de Tumores Neuroendocrinos.