A Study of Axitinib in Advanced Carcinoid Tumors

Carcinoid Tumor Clinical Trial

Official title:

A Phase II Study of Axitinib in Advanced Carcinoid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01435122
• Other study ID #: MCC-16692
• Status: Completed
• Phase: Phase 2
• Start date: October 25, 2011
• Est. completion date: February 13, 2018

Study information

• Verified date: August 2018
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to see whether Axitinib will help prolong the time that the patient's carcinoid tumors remain stable, and to examine their treatment response through testing. Researchers also want to find out if Axitinib is safe and tolerable.

Description:

This is a bi-institutional, prospective phase II, open-label study. The target population is comprised of adult patients with histologically confirmed unresectable or metastatic carcinoid tumors. Carcinoid tumors are defined as well to moderately differentiated neuroendocrine tumors of the digestive tract and lungs. Patients with metastatic carcinoid tumors of unknown primary as well as rare primaries (renal, ovarian, thymic, hepatic) will also be eligible. Patients will be drawn from two institutions Moffitt Cancer Center (MCC) and The University of California, San Francisco (UCSF).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 13, 2018
• Est. primary completion date: January 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally unresectable or metastatic well-and moderately-differentiated (low- or intermediate- grade) neuroendocrine tumors of the aerodigestive tract (e.g. foregut, midgut, and hindgut) and unknown primary site as well as rare primary sites (renal, ovarian, thymic, hepatic); Otherwise known as typical or atypical carcinoid tumors

• Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria

• Functional or nonfunctional tumors allowed

• Evidence of progressive disease within 12 months of study entry

• Adequate hepatic function: total bilirubin =1.5 x upper limit of normal (ULN)mg/dl; aspartic transaminase (AST) =2.5 x ULN (=5 x ULN if attributable to liver metastases)

• Adequate renal function: serum creatinine = 1.5 x ULN

• Adequate bone marrow function: absolute neutrophil count = 1,500/mm³; platelets =75,000/mm³

• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels =1.5 x ULN (unless patients receiving coumadin anticoagulation in which case a stable international normalization ration (INR) of 2-3 is required).

• Urine protein <2+proteinuria (or <2 g proteinuria /24 hr)

• Prior somatostatin-analog therapy required in patients with midgut carcinoid tumors

• Minimum 4 weeks since completion of prior treatment (investigational or other). Prior treatment with chemotherapy, radiotherapy, hepatic artery embolization, surgery or other therapeutic agents is allowed.

• Treatment related toxicity should have returned to baseline and/or =grade 1 prior to study treatment.

• Prior or concurrent therapy with somatostatin analogs is permitted for the control of hormone-mediated symptoms, provided patient has been on a stable dose for at least 2 months and progressive disease on somatostatin analogs (SSTa) has been documented

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to treatment.

• Ability to sign informed consent

• Willingness and ability to comply with scheduled visits, laboratory tests and other study procedures

Exclusion Criteria:

• Poorly differentiated, high-grade (e.g. small cell or large cell) neuroendocrine carcinomas are excluded.

• Pancreatic neuroendocrine tumors (NETs), paragangliomas, pheochromocytomas and medullary thyroid cancers are excluded.

• Adenocarcinoid tumors and goblet cell carcinoid tumors are excluded.

• Prior antiangiogenic therapy with a dedicated vascular endothelial growth factor (VEGF) pathway inhibitor

• Clinically apparent central nervous system metastases

• Any of the following within 12 months prior to study: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack

• Deep venous thrombosis or pulmonary embolism within 6 months of study

• Major surgery 4 weeks prior to enrollment

• Inability to take oral medication or prior surgical procedures affecting absorption (including total gastric resection)

• Active gastrointestinal bleeding, if transfusion dependent

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

• History of pulmonary hemorrhage or evidence of significant hemoptysis

• History of serious non-healing wound, ulcer, or bone fracture within the past 28 days

• Pre-existing thyroid abnormality allowed provided thyroid function can be controlled with medication.

• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, etc.)

• Current use or anticipated need for treatment with drugs that are known inducers of CYP3AR or CYP1A2 (i.e carbamazepine, dexamethasone, omeprazole, phenobarbital, phenytoin, rifampin, St. John's Wart, etc.)

• Uncontrolled serious medical or psychiatric illness. Patients with a "currently active" second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer (staged pathological tumor-2 (pT2) with Gleason Score = 6 and postoperative prostatic specific antigen (PSA) < 0.5 ng/mL), or other adequately treated carcinoma-in-situ are ineligible. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for =3 years.

• Pregnant or lactating women, or adults of reproductive potential who are not using effective birth-control methods.

• Prior antitumor therapy within 4 weeks of enrollment (with exception of somatostatin analogs)

• Liver-directed therapy within 2 months of enrollment. Prior treatment with radiotherapy (including radio-labeled spheres and/or cyberknife, hepatic arterial embolization (with or without chemotherapy) or cryotherapy/ablation is allowed if these therapies did not affect the areas of measurable disease being used for this protocol or if progressive disease can be documented in the previously treated area.

• Recent infection requiring systemic anti-infective treatment that was completed =14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection)

• Uncontrolled hypertension (blood-pressure >140/90). Patient with baseline hypertension may be eligible after initiation of antihypertensive therapy.

Related Conditions & MeSH terms

• Carcinoid Tumor

Intervention

Drug:
• Axitinib
Axitinib Administration as outlined in Arm description

Locations

Country	Name	City	State
United States	University of California San Francisco (UCSF)	San Francisco	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (3)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	National Comprehensive Cancer Network, Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Progression Free Survival (PFS)	Progression-free survival rate at 12 months. PFS: determined as the time from administration of the initial dose of axitinib until objective tumor progression using Response Evaluation Criteria In Solid Tumors (RECIST), or death. Progressive Disease (PD) Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Stable Disease (SD): Neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	12 Months
Primary	Median Progression Free Survival	Post follow-up progression free survival at time of analysis.	Up to 36 Months
Secondary	Tumor Response Rate	Tumor response rate using RECIST. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	12 Months
Secondary	24 Month Overall Survival (OS) Rate	Overall survival by Kaplan Meier, determined from the time of drug administration to death from any cause. The effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death is called as survival time and the analysis of group data as survival analysis.	24 months
Secondary	Time to Treatment Failure	Time to Treatment Failure: Time from administration of the initial dose of axitinib until study discontinuation for any reason (e.g., disease progression, toxicity, death, withdrawal of consent).	12 Months
Secondary	Occurrence of Possibly Related Adverse Events (AEs)	Grade 2 through 4 toxicities considered at least possibly related to treatment. Percentage of participants affected per category. Safety assessments will consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology and blood chemistry parameters and regular physical examinations. Adverse events will be evaluated continuously throughout the study. Safety and tolerability will be assessed according to the National Institute of Health/National Cancer Institute (NIH/NCI) Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.	12 Months

External Links

•   Moffitt Cancer Center Clinical Trials website