Dovitinib Lactate in Treating Patients With Pancreatic Neuroendocrine Tumors

NCT02108782 | Withdrawn Phase 2 DMC

• 2 other identifiers: RU021205INCI-2013-02388
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well dovitinib lactate works in treating patients with pancreatic neuroendocrine tumors. Dovitinib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Confidence intervals for the estimate of 6-month PFS will be calculated using the method of Duffy and Santner.

  6 months

Secondary Outcomes (7)

• Time to treatment failure

  Calculated as the time between registration and the date of ending treatment, assessed up to 3 years

• Time to progression

  Calculated as the time between registration and disease progression, assessed up to 3 years

• Overall survival

  Estimated as the time between registration and death, assessed up to 3 years

• Duration of response

  Time from best response to the date of progressive disease (or date of last disease assessment, for patients having not progressed), assessed up to 3 years

• Biochemical response, classified according to RECIST v1.1

  Up to 3 years

Other Outcomes (3)

• Change in circulating growth factors and soluble receptors (e.g., bFGF, VEGF, PLGF, sVEGFR1 and 2, collagen IV, FGF23)

  Baseline to 30 days after completion of study treatment

• Banking of archival tissue for future research

  Baseline

• Plasma levels of circulating angiogenic factors and soluble receptors

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (dovitinib lactate)

EXPERIMENTAL

Patients receive dovitinib lactate PO on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: dovitinib lactate; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

dovitinib lactate DRUG

Given PO

Also known as: CHIR-258, receptor tyrosine kinase inhibitor TKI258, RTK inhibitor TKI258, TKI258

Treatment (dovitinib lactate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (dovitinib lactate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (dovitinib lactate)

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of a well- to moderately differentiated PNET (low-intermediate grade); NOTE: pathology report should state one of the following: low-grade, intermediate grade, moderately- or well-differentiated NET, pancreatic NET (or neuroendocrine carcinoma of the pancreas); patients who have tumors with a Ki67 of 20 % - 30 % are eligible if the pathologist determines the tumor has the appearance of a well- to moderately differentiated neuroendocrine tumor
• Documented radiological evidence for disease progression (measurable or nonmeasurable) =\< 12 months prior to enrollment; NOTE: if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation; at least one measurable lesion as per Response Evaluation Criteria In Solid Tumors (RECIST)
• Disease that is currently not amenable to surgery, radiation, or combined modality therapy with curative intent
• COHORT 2 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)
• Recovered from adverse events (to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events \[CTCAE\] 4.0) due to agents administered previously; NOTE: chemotherapy-induced alopecia and grade 2 neuropathy are acceptable
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin (Hgb) \> 9 g/dL
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3.0 x ULN
• Serum creatinine =\< 1.5 x ULN
• Provide informed written consent
• Negative pregnancy test done =\< 14 days prior to registration, for women of childbearing potential only
• Willing to return to an Academic and Community Cancer Research United (ACCRU) enrolling institution for follow-up (i.e., active monitoring, which includes active treatment and observation)

You may not qualify if:

• Clinical evidence for brain metastases (including carcinomatous meningitis) at baseline (may require imaging assessment, e.g. computed tomography \[CT\] or magnetic resonance imaging \[MRI\], for certain patient population), with the exception of those subjects who have previously-treated central nervous system (CNS) metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have had no requirement for steroids or enzyme- inducing anticonvulsants within 6 months prior to study entry
• Participated in a prior anticancer investigational study =\< 30 days prior to enrollment, or =\< 5 half-lives of the anticancer investigational product, whichever is longer (treatment with somatostatin analogue \[SSTa\] while on dovitinib is allowed provided patient's tumor has progressed on therapy prior to initiating dovitinib treatment)
• COHORT 1 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)
• Liver-directed therapy (hepatic artery chemoembolization \[HACE\], hepatic artery embolization \[HAE\], selective internal radiation therapy \[SIRT\]) or peptide receptor radionuclide therapy (PRRT) =\< 56 days of first dose of study drug
• Another primary malignancy =\< 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix
• Received the last administration of an anticancer targeted small molecule therapy (e.g. sunitinib, sorafenib, pazopanib, axitinib, everolimus, temsirolimus, ridaforolimus) =\< 14 days prior to study registration or have not recovered from the side effects of such therapy
• Received the last administration of an anticancer monoclonal antibody, immunotherapy, hormonal therapy, or chemotherapy (except nitrosoureas and mitomycin-C) =\< 28 days prior to study registration or who have not recovered from the side effects of such therapy
• Received the last administration of nitrosourea or mitomycin-C =\< 42 days prior to study registration, or who have not recovered from the side effects of such therapy
• Radiotherapy (external beam or CyberKnife) =\< 28 days prior to starting study drug, or =\< 14 days prior to study registration in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
• Undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury =\< 28 days prior to study registration, or had minor procedures, percutaneous biopsies or placement of vascular access device =\< 7 days prior to study registration, or have not recovered from side effects of such procedure or injury
• History of pulmonary embolism (PE), or untreated deep venous thrombosis (DVT) =\< 180 days
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History or presence of serious uncontrolled ventricular arrhythmias
• Clinically significant resting bradycardia
• Ongoing cardiac dysrhythmias, atrial fibrillation, or prolongation of corrected QTc interval to \> 480 msec

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Carcinoma, Islet Cell; Somatostatinoma

Interventions

4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal

Study Officials

• Emily Bergsland

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

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: January 7, 2014
• First Posted: April 9, 2014
• Study Start: October 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: July 19, 2017

Record last verified: 2015-07