Study Evaluating Two Loading Regimens of Sunitinib Alternating With Cisplatin and Gemcitabine as Induction Therapy for Locally Advanced Nasopharyngeal Carcinoma (NPC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01309633
First received: March 3, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Aims:

Primary objectives

  • To determine the pathological complete response (CR)* rate of intermittent sunitinib administered with combination cisplatin and gemcitabine as systemic therapy for locally advanced or systemic NPC.
  • To determine the safety and tolerability of intermittent sunitinib administered with combination cisplatin and gemcitabine as systemic therapy for locally advanced or systemic NPC.

Secondary objectives

  • To determine the clinical response rate (RR; complete and partial response)+ of intermittent sunitinib administered with combination cisplatin and gemcitabine as systemic therapy for locally advanced or systemic NPC.
  • To evaluate the pharmacodynamic effects (imaging, circulating and tissue) of intermittent sunitinib administered with combination cisplatin and gemcitabine as systemic therapy for locally advanced or systemic NPC.
  • To compare the early pharmacodynamic effects (imaging, circulating and tissue) of a loading dose of 12.5mg or 25mg sunitinib for 7 prior to administration of systemic cisplatin and gemcitabine chemotherapy.

Condition Intervention Phase
Nasopharyngeal Carcinoma
Drug: 12.5mg sunitinib with Cisplatin and Gemcitabine
Drug: 25mg Sunitinib alternating with Cisplatin and Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Open-label Study Evaluating Two Loading Regimens of Sunitinib Alternating With Cisplatin and Gemcitabine as Systemic Therapy for Locally Advanced or Metastatic Nasopharyngeal Carcinoma

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • Clinical Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    1. Rates of clinical response (complete and partial clinical response).
    2. Rates of pathological complete responses.
    3. Progression-free survival.
    4. Haematologic and non-haematologic toxicities, as well as serious adverse events.


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A

1) Arm A

Day -6 to Day 0 (total 7 days):

Sunitinib 12.5mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 12.5mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

Drug: 12.5mg sunitinib with Cisplatin and Gemcitabine

1) Arm A

Day -6 to Day 0 (total 7 days):

Sunitinib 12.5mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 12.5mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

Other Name: Sunitinib alternating with Cisplatin and Gemcitabine
Experimental: Arm B

Arm B

Day -6 to Day 0 (total 7 days):

Sunitinib 25mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 25mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

Drug: 25mg Sunitinib alternating with Cisplatin and Gemcitabine

Arm B

Day -6 to Day 0 (total 7 days):

Sunitinib 25mg daily Cycles 1 and 2 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2 Day 15 to Day 21: Sunitinib 25mg daily Cycle 3 - Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2 Day 8: IV Gemcitabine 1000mg/m2

Other Names:
  • Arm B
  • Day -6 to Day 0 (total 7 days):
  • Sunitinib 25mg daily
  • Cycles 1 and 2 -
  • Day 1: IV Gemcitabine 1000mg/m2 + IV Cisplatin 75mg/m2
  • Day 8: IV Gemcitabine 1000mg/m2
  • Day 15 to Day 21: Sunitinib 25mg daily
  • Cycle 3 -

  Eligibility

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

Inclusion Criteria:

  • Patients may be included in the study only if they meet all of the following criteria:

    • Male or female patients aged 21 years and above.
    • Patients with histologically confirmed WHO Type II or III NPC.
    • Tumour stage III, IVA (T4 N0-2 M0) or IVB (Any T N3 M0) or IVC (Any T Any N M1)according to the American Joint Committee on Cancer (AJCC) 2010 criteria. Alternatively, patients with locally advanced recurrent or metastatic NPC for which systemic chemotherapy is indicated will be eligible.
    • Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
    • Adequate organ function including the following:

      a.Bone marrow function i.Haemoglobin = 9g/dl ii.Absolute neutrophil count (ANC) = 1.5 x 109/L iii.Platelet count = 100 x 109/L.

      b.Liver function i.Bilirubin < or = upper limit of normal (ULN) ii.Alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) < or = 2.5x ULN iii.Alanine transaminase (ALT) and aspartate transaminase (AST) < or = ULN iv.Prothrombin time (PT) within the normal range for the institution.

      c.Renal function i.Plasma creatinine within the normal range for the institution or calculated creatinine clearance (by the Cockcroft-Gault formula) > 60mL/min.

      d.Serum amylase and lipase < or = 1.5x ULN.

    • Life expectancy of at least 3 months.
    • Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
    • Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.

Exclusion Criteria:

  • Patients will be excluded from the study for any of the following reasons:

    • Previous or concurrent anti-cancer chemotherapy, immunotherapy, radiotherapy or any other investigational therapy.
    • Patients who cannot swallow or patients with chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
    • Any concomitant condition that could compromise the objectives of this study and/or the patient's compliance (eg. severe medical conditions such as uncontrolled infection, poorly controlled diabetes mellitus, hypercalcaemia, psychiatric disorders).
    • Major thoracic and/or abdominal surgery in the preceding 3 weeks.
    • Known human immunodeficiency virus (HIV) seropositivity, hepatitis B or C seropositivity.
    • In the investigator's opinion, patients with a current or previous history of clinically significant liver disease within the previous 2 years.
    • History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina [anginal symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Cardiac arrhythmias requiring anti-arrhythmic therapy (ß-blockers or digoxin are permitted).
    • Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of = 3 anti-hypertensive drugs or systolic blood pressure greater than 150 mmHg).
    • Dehydration NCI-CTCAE Grade 2 or higher.
    • Subjects with serious non-healing wound, ulcer, or bone fracture.
    • Subjects with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication.
    • Subjects with renal impairment (creatinine clearance by the Cockcroft-Gault formula) = 60mL/min) or on dialysis.
    • Persistent proteinuria of NCI-CTCAE Grade 3 or higher (> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample).
    • Clinically significant bleeding (NCI-CTCAE Grade 3 or higher) within 30 days prior to start of study medication.
    • Subjects unable to swallow oral medications.
    • Subjects with seizure disorder requiring anticonvulsant medication.
    • History of organ allograft.
    • Subjects with evidence or history of disorders of coagulation or thrombosis.
    • Pregnancy or breastfeeding.
    • Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study medication, and a negative result must be documented before start of study medication. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) upon signing the informed consent form until at least 3 months after the last study drug administration. The definition of adequate contraception will be based on the judgment of the treating investigator or a designated associate.
    • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
    • Known or suspected allergy to the investigational agent or any agent given in association with this study.
    • Any condition that is unstable or could jeopardize the safety or compliance of the subject in the study.
    • Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 3 years prior to study entry.
    • Interstitial lung disease with ongoing signs and symptoms at the time of screening.
  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: NCT01309633

Contacts
Contact: Boon Cher Goh, MBBS +65 6779 5555 Boon_Cher_Goh@nuhs.edu.sg
Contact: Christine Vergara (65) 6772 4619 christine_vergara@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Kent Ridge, Singapore, 119074
Contact: Boon Cher Goh, MBBS    (65) 6772 4140    Boon_Cher_Goh@nuhs.edu.sg   
Contact: Christine Vergara    (65) 6772 4619    christine_vergara@nuhs.edu.sg   
Sub-Investigator: Boon Cher Goh, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Boon Cher Goh, MBBS National University Hospital, Singapore
  More Information

No publications provided

Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01309633     History of Changes
Other Study ID Numbers: NP01/27/10
Study First Received: March 3, 2011
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority

Keywords provided by National University Hospital, Singapore:
locally advanced
metastatic

Additional relevant MeSH terms:
Carcinoma
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Gemcitabine
Sunitinib
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014