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

Grupo Espanol de Tumores Neuroendocrinos9 sites in 1 country21 target enrollmentMay 2015

ConditionsPancreatic Neuroendocrine Cancer

InterventionsPalbociclib

DrugsPalbociclib

Overview

Phase: Phase 2
Intervention: Palbociclib
Conditions: Pancreatic Neuroendocrine Cancer
Sponsor: Grupo Espanol de Tumores Neuroendocrinos
Enrollment: 21
Locations: 9
Primary Endpoint: Activity of palbociclib (PD0332991) considering objective response rate
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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)

Detailed Description

The purpose of this study is to evaluate 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)

Registry

clinicaltrials.gov

Start Date

May 2015

End Date

January 2018

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Grupo Espanol de Tumores Neuroendocrinos

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•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.

Exclusion Criteria

•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.

Arms & Interventions

Palbociclib

Intervention: Palbociclib

Outcomes

Primary Outcomes

Activity of palbociclib (PD0332991) considering objective response rate

Time Frame: 20 months

Secondary Outcomes

Duration of response(Patients will be followed until disease progression, estimating around 12 months)
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)
Positive expression of tumor biomarkers (Cdk4, Cdk6, fosfo-Rb1, D1 cyclin, p53, Ki67)(Positive expression of tumor biomarkers at baseline)
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)