| ATTRACT-1 is a phase III, randomized, double-blind, placebo-controlled multicenter study of ASA404 in combination with paclitaxel and carboplatin as first-line cancer treatment for locally advanced or metastatic (stage IIIb/IV) non-small cell lung cancer (NSCLC). |
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What is ASA404?
ASA404, a flavone-8-acetic acid analogue, is a novel Tumor-Vascular Disrupting Agent (Tumor-VDA) that acts on established tumor vasculature. By inducing apoptosis of tumor vascular endothelial cells and cytokine production, ASA404 causes disruption of tumor blood vessels, inhibition of tumor blood flow and extensive tumor necrosis.
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What is the rationale for using ASA404 in
combination with paclitaxel and carboplatin for cancer treatment?
The antitumor effect seen with ASA404 has been shown to increase synergistically when combined with paclitaxel and carboplatin due to synergy with taxanes. It is thought that synergistic tumor cell killing occurs as ASA404 acts on poorly perfused regions of the tumor that are inaccessible to other chemotherapeutic agents used in cancer treatment.
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What is the rationale for testing this cancer treatment in patients with non-small cell lung cancer (NSCLC)?
While platinum-based doublets such as paclitaxel/carboplatin are generally accepted as standard therapy for advanced NSCLC, these cancer treatment regimens yield response rates of only around 19%, with median survival of approximately 8 months. As a Tumor-VDA, ASA404 has a unique mode of action and has shown synergistic activity in combination with taxanes. In a phase Ib/II clinical trial of ASA404 for the first-line treatment of patients with stage IIIb or IV NSCLC, presented at the 2006 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, the addition of ASA404 to paclitaxel and carboplatin increased median survival among these lung cancer patients 5.2 by months.
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What is the primary objective of the ATTRACT-1 clinical trial?
The primary objective of the ATTRACT-1 clinical trial is to compare the overall survival of patients receiving ASA404 or placebo in combination with paclitaxel and carboplatin for first-line treatment of stage IIIb/IV NSCLC.
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What are the secondary objectives of the ATTRACT-1 clinical trial?
- To compare the overall survival of lung cancer patients with non-squamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin.
- To compare the overall survival of lung cancer patients with squamous NSCLC receiving ASA404 or placebo in combination with paclitaxel and carboplatin.
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Are there other objectives of this trial?
ATTRACT-1 has a number of other key objectives, including:
- To assess the safety of ASA404 in combination with paclitaxel/carboplatin.
- To compare the overall response rate and progression-free survival, and to determine time to overall response and duration of overall response between non-small cell lung cancer patients receiving ASA404 or placebo in combination with paclitaxel and carboplatin for cancer treatment.
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Who is eligible for the ATTRACT-1 clinical trial?
Adult patients, 18 years of age or older, with newly diagnosed or recurrent stage IIIb/IV NSCLC of all histologic types, who have never been treated with first-line chemotherapy are eligible.
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Can a patient who has been treated previously
for NSCLC participate in the ATTRACT-1 clinical trial?
A patient who has been treated for earlier-stage NSCLC (stage I/II) 12 months or more prior to baseline visit is allowed to participate in ATTRACT-1. Patients who have received treatment for stage IIIb/IV NSCLC are not eligible.
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What is the time commitment for lung cancer patients
participating in this trial?
A treatment cycle is 21 days and patients will receive up to six cycles of combination therapy. Patients who complete 6 cycles of cancer treatment without progressive disease will continue to receive blinded ASA404 or placebo as maintenance treatment until disease progression. All patients, regardless of whether or not they discontinued prior or subsequent to disease progression, will be followed every six weeks for overall survival or until the date of data cut-off.
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What happens if a patient discontinues the trial
or withdraws consent?
Patients who discontinue the study treatment for reasons other than documented disease progression will continue to have tumor assessments performed every six weeks until documented disease progression or the start of a new chemotherapy. Patients who withdraw consent and do not wish to have radiological assessments will be followed for survival every six weeks.
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Can ATTRACT-1 study participants receive supportive therapies during the trial?
Therapies considered as supportive care, including granulocyte colony stimulating factor, palliative radiation, and bisphosphonates for bone metastasis, are acceptable for patients participating in the ATTRACT-1 clinical trial.
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Are there any therapies that should not be
administered concomitantly while patients are participating in this trial?
The use of drugs that pose a potential risk of prolonging the QT interval and/or inducing Torsades de Pointes ventricular arrhythmia should be avoided throughout this trial. If the use of these medications is deemed medically necessary by the investigator, study treatment should be discontinued and the patient followed radiologically every six weeks for RECIST (Response Evaluation Criteria in Solid Tumors) until documented disease progression and then for overall survival. However, the investigator is encouraged to contact the Novartis medical monitor and discuss all treatment options for patients prior to discontinuation of study treatment.
As ASA404 is known to cause an increase of serotonin levels in the blood, the investigator must exercise caution and refrain from administering any other drugs that are known or suspected to raise serotonin levels, particularly antidepressants, due to the risk of “serotonin syndrome.” In addition, the investigator must exercise caution and refrain from administering nitrates and alpha blockers as they may cause symptomatic hypotension due to the known phosphodiesterase pharmacological activity of ASA404.
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How is the cancer treatment administered?
All cancer treatments will be administered on day one of each cycle. Patients will receive a three-hour intravenous (IV) infusion of 200 mg/m2 paclitaxel followed by a 30-minute IV infusion of carboplatin AUC 6. Patients will then receive a 20-minute IV infusion of ASA404 or placebo.
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What side effects might patients experience as a result of the cancer treatment?
In a phase II study assessing 1800 mg/m2 ASA404 in combination with paclitaxel and carboplatin, combination treatment demonstrated a safety profile similar to that seen with paclitaxel and carboplatin alone (standard therapy). Common side effects included alopecia, nausea, fatigue, vomiting, myalgia and neutropenia in the standard therapy group, and nausea, infusion site pain, fatigue, alopecia, peripheral neuropathy and neutropenia in the ASA404 1800 mg/m2 group.
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In case of adverse events, are dose reductions or treatment delays allowed?
Dose adjustments for ASA404 are not permitted. Study drug must always be given following the standard chemotherapy. Delays in treatment cycle and dose reductions to paclitaxel and/or carboplatin are permitted and will be based on the worst toxicity seen during the previous treatment cycle. If there is a need to delay the treatment cycle, ASA404 will also be delayed until the chemotherapy is given.
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How will efficacy of the treatment regimens in the ATTRACT-1 clinical trial
be evaluated?
Radiological assessments of NSCLC tumors will be performed at baseline and repeated every six weeks during the treatment phase until disease progression occurs. RECIST will be used to document tumor response, disease progression, time to either disease progression or time to response and duration of response. Overall survival will be calculated based on the date of randomization and the date of death or last date of contact.
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Is there a cost to my patients to participate in
the ATTRACT-1 clinical trial?
No. All procedures that are required as part of ATTRACT-1 and that are not standard of care will be covered.
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Where is the ATTRACT-1 trial being conducted?
This trial is being conducted at a large number of sites worldwide. For a list of participating countries, please visit www.attractstudy.com or call the Novartis Oncology Clinical Trials Hotline at 1-800-340-6843.*
* For countries outside the United States, please contact your local Novartis representative for more information.
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How many patients will be treated in this trial?
The planned accrual for ATTRACT-1 is 1,200 non-small cell lung cancer patients.
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How can I enroll NSCLC patients in ATTRACT-1?
For further information or to enroll patients in this clinical trial, please visit www.attractstudy.com or contact your local Novartis representative.
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