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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Randomized Study of Docetaxel With or Without Low-dose, Short Course Sunitinib in the Treatment of Advanced Solid Tumors

Conditions
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Solid Tumors, Breast Cancer, Non-small Cell Lung Cancer, Prostate Cancer, Gastric Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Docetaxel<br>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<br>* Docetaxel 75mg/m2 day 1, every 3 weeks<br>|
| Experimental: Docetaxel + Sunitinib<br>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<br>* Docetaxel 75mg/m2 day 1, every 3 weeks<br>Drug: Sunitinib<br>* 7 days of sunitinib 12.5mg orally daily during each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 18 weeks | 
| Clinical benefit rate | 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. | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 18 weeks until documented disease progression |