A Trial to Assess the Activity and Safety of Palbociclib in Patients With Well and Moderately Differentiated Metastatic Pancreatic Neuroendocrine Tumors (pNET)

NCT02806648 | Completed Phase 2 DMC

• 1 other identifier: GETNE-1407
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 9

Brief Summary

A phase II trial to assess the activity and safety of PD0332991 in patients with well- and moderately-differentiated metastatic pancreatic neuroendocrine tumors (pNET) with overexpression of cell cycle markers (Cdk4 and/or phospho-Rb1 and/or cyclin D1)

Conditions

Pancreatic Neuroendocrine Cancer

Outcome Measures

Primary Outcomes (1)

• Activity of palbociclib (PD0332991) considering objective response rate

  20 months

Secondary Outcomes (6)

• Progression Free Survival

  Patients will be followed until disease progression, estimating around 12months

• Time to Tumor Progression

  Patients will be followed until disease progression, estimating around 12 months

• Duration of response

  Patients will be followed until disease progression, estimating around 12 months

• Overall Survival

  Patients will be followed until death, estimating around 33 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (Safety)

  Patients will be followed until disease progression estimating around 12 months

Study Arms (1)

Palbociclib

EXPERIMENTAL

Palbociclib

Drug: Palbociclib

Interventions

Palbociclib DRUG

Palbociclib

Also known as: palbociclib (PD0332991)

Palbociclib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven diagnosis of pancreatic neuroendocrine tumors (pNET) with Ki67 assessment of \< or = 20% (well and moderately differentiated) with evidence of unresectable disease or metastatic disease. Locally advanced disease must not be amendable to resection or radiation therapy with curative intent.
• Overexpression of Cdk4 and/or phospho-Rb1 and/or cyclin D1 in tumor tissue sample from tumor biopsy or prior primary tumor resection (Molecular study will be conducted at CNIO and logistic is described later). Therefore availability of paraffin-embedding tumor tissue sample is needed.
• Documented progression of the disease by CT scan, MRI, or Octreoscan within 12 months prior to baseline.
• Previous treatments with chemotherapy, antiangiogenics, or interferon are permitted providing that toxicity has resolved to \< grade 1 at study entry and that last treatment was at least 4 weeks prior to baseline assessment. Patients may be treated with somatostatin analogues during the trial. Concomitant interferon treatment is not permitted.
• Measurable disease as per RECIST. Measurable lesions that have been previously radiated will not be considered target lesions unless increase in size has been observed following completion of radiation therapy.
• Able to swallow oral compound
• Male or female, 18 years of age or older.
• ECOG performance status less than 2.
• Life expectancy greater than 12 weeks.
• The definitions of minimum adequacy for organ function required prior to study entry are as follows. In addition, safety precautions provided in the product labeling for the anticipated control arm chemotherapy must be observed.
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) 2.5 x upper limit of normal (ULN), or AST and ALT 5 x ULN if liver function abnormalities are due to underlying malignancy
• Total serum bilirubin 1.5 x ULN
• Serum albumin 3.0 g/dL
• Absolute neutrophil count (ANC) 1500/L
• Platelets 100,000/L

You may not qualify if:

• Prior chemotherapy regimen or biological treatment for locally advanced or metastatic transitional cell carcinoma of the urinary tract.
• Prior treatment on Cdk4 inhibitor under clinical trial.
• Creatinine clearance \< 40 ml/min using Cockroft and Gault formula.
• Major surgery, radiation therapy, or systemic therapy within 3 weeks of study randomization except palliative radiotherapy to non-target metastatic lesions.
• Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
• Immunosuppressive drugs such as cyclosporine, tacrolimus, azathioprine, or long-term oral glucocorticoids taken concurrently or within last 3 months prior to randomization
• Prior radiation therapy to \>25% of the bone marrow.
• Current treatment on another clinical trial.
• Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. Patients should have completed surgery or radiation therapy for existing brain metastases, should not have documented increase in size over the previous 3 months prior to first dose of treatment on study and should be asymptomatic.
• Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus.
• Ongoing cardiac dysrhythmias of NCI CTCAE grade 2, atrial XML File Identifier: 3xAP+CVEwV9UnEoC7xvloFQA/XQ=Page 20/34 fibrillation of any grade, or QTc interval \>450 msec for males or \>470msec for females.
• Hypertension that cannot be controlled by medications (\>150/100mmHg despite optimal medical therapy)
• Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
• Known human immunodeficiency virus infection.

Sponsors & Collaborators

• Grupo Espanol de Tumores Neuroendocrinos: lead

Study Sites (9)

ICO

L'Hospitalet de Llobregat, Barcelona, Spain

Location

C. H. de Navarra

Pamplona, Navarre, Spain

Location

H.U.C de Asturias

Oviedo, Principality of Asturias, Spain

Location

H. Vall d´Hebron

Barcelona, Spain

Location

H. Castellon

Castelló, 12002, Spain

Location

H U Ramón y Cajal

Madrid, Spain

Location

H. 12 Octubre

Madrid, Spain

Location

H.U.La Paz

Madrid, Spain

Location

H.U.Virgen del Rocio

Seville, Spain

Location

MeSH Terms

Conditions

Somatostatinoma

Interventions

palbociclib

Condition Hierarchy (Ancestors)

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

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: July 8, 2015
• First Posted: June 20, 2016
• Study Start: May 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: January 1, 2018
• Last Updated: January 23, 2018

Record last verified: 2016-06

Locations

ES (9)