Docetaxel With or Without Low-dose, Short Course Sunitinib in Refractory Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National University Hospital, Singapore
Sponsor:
Information provided by (Responsible Party):
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01803503
First received: March 1, 2013
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

This study aims to find out whether the effect of docetaxel chemotherapy may be improved by combining it with another anti-cancer drug called sunitinib, which stops blood vessels from growing (anti-angiogenic agent). Sunitinib is an oral anti-angiogenic drug that has been approved for the treatment of kidney cancer, a rare form of soft tissue tumor called gastrointestinal stromal tumor, and a rare form of cancer in the pancreas called pancreatic neuroendocrine tumor. Sunitinib is usually given continuously at a dose of 37.5mg (3 pills) daily either alone or in combination with chemotherapy. However, there are studies which have shown that the continuous administration of sunitinib may reduce chemotherapy effectiveness. On the other hand, a short course of sunitinib before each chemotherapy cycle may sensitize the tumor to chemotherapy. This treatment strategy will be used in patients with different kinds of cancers with a commonly used chemotherapy drug, docetaxel. Ths study aims to evaluate if intermittent administration of low dose sunitinib before docetaxel chemotherapy can improve the treatment response in cancer patients.

Study Hypothesis: Low dose, short course sunitinib at 12.5mg daily orally for 1 week prior to chemotherapy can normalize tumor vasculature and enhance delivery of chemotherapy into the tumor, and improve treatment response and progression-free survival.


Condition Intervention Phase
Solid Tumors
Breast Cancer
Non-small Cell Lung Cancer
Prostate Cancer
Gastric Cancer
Drug: Docetaxel
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Study of Docetaxel With or Without Low-dose, Short Course Sunitinib in the Treatment of Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Clinical benefit rate [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    Clinical benefit rate is defined as the proportion of patients who achieved complete response, partial response, or stable disease for at least 12 weeks, as the best response.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 18 weeks until documented disease progression ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: May 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Docetaxel
Docetaxel 75mg/m2 day 1, every 3 weeks. Patients will be treated for a maximum of 6 cycles of chemotherapy in the absence of tumor progression or unacceptable toxicities.
Drug: Docetaxel
Docetaxel 75mg/m2 day 1, every 3 weeks
Experimental: Docetaxel + Sunitinib

Docetaxel 75mg/m2 day 1, every 3 weeks, preceded by 7 days of sunitinib 12.5mg orally daily during each cycle.

Patients will be treated for a maximum of 6 cycles of chemotherapy in the absence of tumor progression or unacceptable toxicities.

Drug: Docetaxel
Docetaxel 75mg/m2 day 1, every 3 weeks
Drug: Sunitinib
7 days of sunitinib 12.5mg orally daily during each cycle

Detailed Description:

This is a single-centre, phase II randomized study. Eligible patients will be randomized to docetaxel with or without intermittent sunitinib. A total of eighty patients with measurable tumor will be enrolled over a period of 24-36 months. Eligible patients will be randomized 1:1 to either arm A or arm B. Patients will be stratified according to site of primary tumor (breast vs non-small cell lung cancer vs others) for randomization purposes.

Arm A (Control arm):

Docetaxel 75mg/m2 day 1, every 3 weeks

Arm B (Experimental arm):

Docetaxel 75mg/m2 day 1, every 3 weeks, preceded by 7 days of sunitinib 12.5mg orally daily during each cycle.

Patients will be treated for a maximum of 6 cycles of chemotherapy in the absence of tumor progression or unacceptable toxicities.

Patient will be evaluated weekly for toxicity assessments and full blood count during cycle 1, and on days 1 and 15 of each subsequent cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years.
  • Histologic or cytologic diagnosis of carcinoma.
  • Measurable tumor, defined as clinically palpable tumor with both diameters 2.0cm or greater as measured by caliper, or radiologically measurable tumor on CT scan with the largest diameter >= 1cm.
  • Eastern Cooperative Oncology Group 0-1
  • Estimated life expectancy of at least 12 weeks.
  • Adequate organ function including the following:

    - Bone marrow: Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100 x 109/L

    - Hepatic: Bilirubin <= 1.5 x upper limit of normal (ULN), ALT or AST <= 2.5x ULN, (or <=5x with liver metastases)

    - Renal: Creatinine <= 1.5x ULN

  • Signed informed consent from patient or legal representative.
  • Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.

Exclusion Criteria:

  • Treatment within the last 28 days with any investigational drug.
  • Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
  • Major surgery within 28 days of study drug administration.
  • Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  • Pregnancy.
  • Breast feeding.
  • Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
  • Active bleeding disorder or bleeding site.
  • Non-healing wound.
  • Poorly controlled diabetes mellitus.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
  • Symptomatic brain metastasis.
  • History of significant neurological or mental disorder, including seizures or dementia.
  • Known history of systemic connective tissue diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis), vasculities (e.g., giant cell arteritis, Kawasaki disease, Wegener's granulomatosis, Churg-Strauss disease) or sickle cell disease.
  • Known history of renal impairment, defined as a Glomerular Filtration Rate (GFR) of less than 30ml/minute.
  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: NCT01803503

Contacts
Contact: Soo Chin Lee, MBBS (65) 6772 4629 soo_chin_lee@nuhs.edu.sg
Contact: Christine Vergara, BS Bio & RN (65) 6772 4619 christine_vergara@nuhs.edu.sg

Locations
Singapore
National University Hospital Not yet recruiting
Singapore, Singapore, 119074
Contact: Soo Chin Lee, MBBS    (65) 6779 5555    soo_chin_lee@nuhs.edu.sg   
Principal Investigator: Soo Chin Lee, MBBS         
National University Hospital Recruiting
Singapore, Singapore, 119228
Contact: Soo Chin Lee, MBBS    +65 6779 5555    soo_chin_lee@nuhs.edu.sg   
Principal Investigator: Soo Chin Lee, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Soo Chin Lee, MBBS National University Hospital, Singapore
  More Information

Publications:
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT01803503     History of Changes
Other Study ID Numbers: BR01/08/13, 2013/00170
Study First Received: March 1, 2013
Last Updated: October 13, 2014
Health Authority: Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms
Stomach Neoplasms
Breast Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Breast Diseases
Carcinoma, Non-Small-Cell Lung
Genital Diseases, Male
Prostatic Diseases
Carcinoma, Bronchogenic
Lung Diseases
Respiratory Tract Diseases
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Skin Diseases
Docetaxel
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators

ClinicalTrials.gov processed this record on October 19, 2014