A Study of Axitinib in Advanced Carcinoid Tumors

NCT01435122 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MCC-16692
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Carcinoid Tumor

Keywords

progressive advanced carcinoid tumors; advanced; unresectable; metastatic; cancerous tumors; neuroendocrine; digestive tract; lungs; renal; ovarian; thymic; hepatic

Outcome Measures

Primary Outcomes (2)

• 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

• Median Progression Free Survival

  Post follow-up progression free survival at time of analysis.

  Up to 36 Months

Secondary Outcomes (4)

• Tumor Response Rate

  12 Months

• 24 Month Overall Survival (OS) Rate

  24 months

• Time to Treatment Failure

  12 Months

• Occurrence of Possibly Related Adverse Events (AEs)

  12 Months

Study Arms (1)

Axitinib Administration

EXPERIMENTAL

The investigational drug used in this study is axitinib, and is available as tablets. You will take the tablet orally with food. Doses should be taken around 12 hours apart continuously, without scheduled breaks. If you vomit anytime after taking a dose do not take another tablet to "make up the dose" but instead continue taking your next dose as planned. Any missed dose may be taken late (up to 3 hours before the next scheduled dose); otherwise it should be skipped. If doses are missed or vomited, please keep track of this and report at your next visit.

Drug: Axitinib

Interventions

Axitinib DRUG

Axitinib Administration as outlined in Arm description

Also known as: AG013736, selective inhibitor of receptor tyrosine kinases

Axitinib Administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Comprehensive Cancer Network: collaborator
• Pfizer: collaborator

Study Sites (2)

University of California San Francisco (UCSF)

San Francisco, California, 94115, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Carcinoid Tumor; Neoplasm Metastasis

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Results are limited by a relatively high rate of participant withdrawal before progression due to toxicity. Post analysis, 2 participants are still on study at UCSF.

Results Point of Contact

• Title: Dr. Jonathan R. Strosberg
• Organization: H. Lee Moffitt Cancer Center and Research Institute

jonathan.strosberg@moffitt.org

813-745-3636

Study Officials

• Jonathan Strosberg, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2011
• First Posted: September 15, 2011
• Study Start: October 25, 2011
• Primary Completion: January 11, 2017
• Study Completion: February 13, 2018
• Last Updated: October 2, 2018
• Results First Posted: May 25, 2017

Record last verified: 2018-08

Locations

US (2)