Pazopanib in Treating Patients With Advanced Neuroendocrine Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00454363
First received: March 27, 2007
Last updated: April 9, 2014
Last verified: December 2013
  Purpose

This phase II trial is studying how well pazopanib works in treating patients with advanced neuroendocrine cancer. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
Gastrinoma
Glucagonoma
Insulinoma
Metastatic Gastrointestinal Carcinoid Tumor
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia Type 2
Pancreatic Polypeptide Tumor
Pulmonary Carcinoid Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Islet Cell Carcinoma
Regional Gastrointestinal Carcinoid Tumor
Somatostatinoma
WDHA Syndrome
Drug: pazopanib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GW786034 (Pazopanib) in Advanced Low-Grade or Intermediate-Grade Neuroendocrine Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate (complete and partial response) for each cohort assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma trough level of GW786034 [ Time Frame: Baseline and day 28 ] [ Designated as safety issue: No ]
  • Progression free survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Change in tumor blood flow assessed by functional CT [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: March 2007
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral pazopanib hydrochloride once daily on days 1-28.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient

Detailed Description:

PRIMARY OBJECTIVE:

I. Determine the objective response rate (complete and partial response) in patients with low- or intermediate-grade advanced neuroendocrine carcinoma treated with pazopanib hydrochloride.

SECONDARY OBJECTIVES:

I. Determine the progression-free survival of patients treated with this drug. II. Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type (carcinoid tumors vs islet cell carcinoma).

Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for up to 18 months.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • At least 4 weeks since prior major surgery
  • No CYP2C9 inhibitors for 14 days prior to, during, and for 2 weeks after completion of study therapy, including any of the following:

Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, nateglinide) Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine) Neuroleptics (e.g., pimozide)

  • No CYP2C9 inhibitors for 14 days prior to, during, and for 2 weeks after completion of study therapy, including any of the following: Erectile dysfunction agents (e.g., sildenafil, tadalafil, vardenafil) Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletine hydrochloride, amiodarone, quinidine, propafenone) Immune modulators (e.g., cyclosporine, tacrolimus, sirolimus)
  • No CYP2C9 inhibitors for 14 days prior to, during, and for 2 weeks after completion of study therapy, including any of the following: Theophylline Quetiapine Risperidone Tacrine Clozapine Atomoxetine
  • No concurrent therapeutic warfarin Low molecular weight heparin or prophylactic low-dose warfarin allowed provided inclusion criteria for PT and PTT are met
  • No concurrent grapefruit or its juice
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
  • No concurrent antiretroviral therapy for HIV-positive patients
  • No concurrent interferon for control of carcinoid syndrome
  • WBC >= 3,000/mm³

Inclusion Criteria:

  • Histologically or cytologically confirmed low or intermediate grade carcinoid or islet cell carcinoma. Carcinoid or islet cell carcinoma associated with MEN1 syndrome will be eligible and entered in the islet cell cohort.
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20 mm with conventional techniques or as >/= 10 mm with spiral CT scan.
  • Received 0, or 1 prior cytotoxic therapy. Chemotherapy used as a radiosensitizer will be considered one prior chemotherapy regimen. Must not have received prior bevacizumab or any other therapy targeting VEGF or VEGF receptors (ie, SU11248, PTK787/ZK222584, Sorafenib, GW786034).
  • Must be on a stable dose (the same dose) of a somatostatin analogue (Lanreotide, Octreotide or Vapreotide) for 2 months prior to start of protocol. A somatostatin analogue does not count toward prior therapy.
  • Prior radiation therapy is permitted. A recovery period of at least 4 weeks after completion of radiotherapy is required prior to enrollment.
  • Received prior interferon (not counted toward prior cytotoxic chemotherapy).
  • Received prior therapy targeting c-kit, abl, PDGFR, or EGFR (imatinib, gefitinib, erlotinib, cetuximab; not counted toward prior cytotoxic chemotherapy).
  • Age >/= 21 years. GW786034 (pazopanib) is contraindicated in the pediatric population due to the potential effect on the epiphyseal growth plates.
  • Must have unresectable or metastatic disease.
  • ECOG performance status of 0, or 1 (Karnofsky >/= 70%).
  • Must have normal organ and marrow function as defined below: Leukocytes >/= 3,000/mcL; absolute neutrophil count >/= 1,500/mcL; platelets >/= 120,000/mcL; total bilirubin within normal institutional limits; AST(SGOT)/ALT(SGPT) </= 3.0 X institutional upper limit of normal; creatinine </= 2.0 OR creatinine clearance >/= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. (Calculated by Cockcroft Gault formula)
  • Must have PT/INR/PTT within 1.2 X the upper limit of normal.
  • Must have resting blood pressure (BP) no greater than 140 mmHg (systolic) or 90 mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted prior to study entry.
  • The effects of GW786034 (pazopanib) on the developing human fetus are unknown. However, teratogenic effects and reduced fetal body weight have been seen in pregnant rats and/or rabbits given GW786034 (pazopanib). For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
  • Women of child-bearing potential must have a negative blood pregnancy test prior to study entry. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: An intrauterine device with a documented failure rate of less than 1% per year; Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female;
  • Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows; Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 21 days after the last dose of investigational product; Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). Oral contraceptives are not reliable due to potential drug-drug interaction.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to swallow and retain oral medication
  • Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

  • Have had chemotherapy or radiotherapy within 4 weeks prior to study enrollment. At least 4 weeks must have elapsed since any major surgery prior to study enrollment.
  • May not be receiving any other investigational agents.
  • With QTc > 480msecs
  • With greater than +1 (>/= 100 mg/dl) proteinuria on two consecutive routine urinalyses taken at least 1 week apart are ineligible.
  • Certain medications that act through the CYP450 system are specifically prohibited in patients receiving GW786034 (pazopanib) because in vitro data indicate that the agent has the potential to interact with the cytochrome P450 isoenzymes. Certain other agents should be used with caution. A list of medications that are specifically prohibited or that should be used with caution during this trial of GW786034 (pazopanib) can be found in Section 8. Selected lists of agents that could affect GW786034 (pazopanib) through the cytochrome P450 system can be found in Appendix II.
  • With any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain GSK786034 (pazopanib) tablets are excluded.
  • With any of the following conditions are excluded: Serious or non-healing wound, ulcer, or bone fracture; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment; History of known active diverticulitis within the past 3 months; Any history of cerebrovascular accident (CVA) within the last 6 months; Current use of therapeutic warfarin.(Low molecular weight heparin and prophylactic low-dose warfarin are permitted); PT/PTT must meet the inclusion criteria.
  • With any of the following conditions are excluded: History of myocardial infarction, cardiac arrhythmia, admission for unstable angina, cardiac angioplasty or stenting within the last 12 weeks; History of venous thrombosis in last 12 weeks; Class III or IV heart failure as defined by the NYHA functional classification system; A patient who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible.
  • With known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
  • Pregnant women are excluded from this study because GW786034 (pazopanib) is an antiangiogenic agent which has produced teratogenic effects and reduced fetal body weight in pregnant rats and/or rabbits, and therefore has the potential for teratogenic or abortifacient effects in humans. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GW786034 (pazopanib), breastfeeding should be discontinued if the mother is treated with GW786034 (pazopanib). These potential risks may also apply to other agents used in this study.
  • HIV-positive on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GW786034 (pazopanib).
  • Uncontrolled diarrhea (8 or more bowel movements per day)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454363

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: James Yao M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00454363     History of Changes
Other Study ID Numbers: NCI-2009-00201, NCI-2009-00201, CDR0000537034, MDACC 2006-0077, MDACC 2006-0077, 7650, U01CA062490, P30CA016672, N01CM62202
Study First Received: March 27, 2007
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gastrinoma
Carcinoid Tumor
Carcinoma
Carcinoma, Islet Cell
Endocrine Gland Neoplasms
Gastrointestinal Neoplasms
Glucagonoma
Insulinoma
Malignant Carcinoid Syndrome
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 1
Multiple Endocrine Neoplasia Type 2a
Neoplasms
Somatostatinoma
Adenocarcinoma
Adenoma
Adenoma, Islet Cell
Carcinoma, Neuroendocrine
Digestive System Diseases
Digestive System Neoplasms
Endocrine System Diseases
Gastrointestinal Diseases
Genetic Diseases, Inborn
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Multiple Primary
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary

ClinicalTrials.gov processed this record on October 22, 2014