Suspended

Induction Chemotherapy Using Doxorubicin and Cisplatin Followed by Combretastatin A4 Phosphate and Radiation Therapy in Treating Patients With Newly Diagnosed Regionally Advanced Anaplastic Thyroid Cancer

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What is being tested

filgrastim

+ pegfilgrastim
+ cisplatin
Biological
Drug
Radiation
Who is being recruted

Head and Neck Cancer

Over 18 Years
How is the trial designed

Treatment Study

Phase 1
Interventional
Study Start: November 2003

Summary

Principal SponsorCase Comprehensive Cancer Center
Last updated: June 11, 2010
Sourced from a government-validated database.Claim as a partner
Study start date: November 1, 2003Actual date on which the first participant was enrolled.

RATIONALE: Drugs used in chemotherapy, such as doxorubicin and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combretastatin A4 phosphate may stop the growth of cancer by stopping blood flow to the tumor. Combining doxorubicin and cisplatin with radiation therapy and combretastatin A4 phosphate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving induction chemotherapy using doxorubicin and cisplatin together with radiation therapy and combretastatin A4 phosphate works in treating patients with newly diagnosed regionally advanced anaplastic thyroid cancer. OBJECTIVES: Primary * Determine the objective response rate in patients with newly diagnosed regionally advanced anaplastic thyroid cancer treated with induction chemotherapy comprising doxorubicin and cisplatin followed by combretastatin A4 phosphate (CA4P) and radiotherapy. * Determine whether this regimen alters the natural history of anaplastic thyroid cancer by virtue of doubling the median survival of these patients from 10 to 20 months. Secondary * Determine a tolerable dose of CA4P when administered with radiotherapy in these patients. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P) * Determine the safety profile of this regimen in these patients. * Determine clinical predictors of response (e.g., pretreatment tumor microvessel density and immature vessel staining, changes in sICAM-1 levels and tumor blood flow, and pharmacokinetic parameters) in patients treated with this regimen. * Correlate the diminution in blood flow with tumor pain and response in patients treated with this regimen. OUTLINE: This is a multicenter study of combretastatin A4 phosphate (CA4P). (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P) * Induction phase: Patients receive doxorubicin IV over 5-10 minutes and cisplatin IV over 30-60 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 3-21 or pegfilgrastim SC on day 2. * Combined modality phase: Beginning on day 22, patients undergo radiotherapy twice daily, 5 days a week, for 3-4 weeks. Patients also receive CA4P IV over 10 minutes weekly on the fifth day of radiotherapy. Cohorts of 6 patients receive 1 of 2 escalating doses of CA4P to determine a tolerable dose. The tolerable dose is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity. (Phase I portion of the study closed as of 5/6/04; patients now receive a fixed dose of CA4P) * Consolidation phase: Beginning 4-6 weeks after the completion of the combined modality phase, patients receive CA4P IV over 10 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses. Treatment in all phases continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year and then every 3 months for 2 years from study entry. PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study within 18 months.

Official TitlePhase II Trial of Combined Modality Combretastatin A-4 Phosphate (CA4P)-Based Therapy for Patients With Newly Diagnosed Anaplastic Thyroid Cancer [Induction Chemotherapy With Doxorubicin/Cisplatin; Combined Modality Therapy With CA4P and Radiation; Followed by 2 Cycles of CA4P Consolidation] 
Principal SponsorCase Comprehensive Cancer Center
Last updated: June 11, 2010
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
4 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation
: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.

Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment
: Participants are split into separate groups, each receiving a different treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Head and Neck Cancer
Criteria

DISEASE CHARACTERISTICS: * Histologically confirmed anaplastic or poorly differentiated variant thyroid carcinoma of either of the following: * Regionally advanced disease * Confined to the neck and/or superior mediastinum (i.e., above the level of the carina) * Measurable or evaluable\* disease * Completely resected disease without measurable or evaluable disease NOTE: \*At a minimum, abnormalities on physical exam or radiographic studies that may not be precisely measured but readily followed * Must have original/diagnostic tumor blocks available to confirm histopathology and for tumor microvessel density immunohistochemistry * Patients with no available original/diagnostic tumor blocks must have tumor accessible for pretreatment needle core biopsy * Must undergo indirect and direct laryngoscopy to ensure patency of the trachea/airway if deemed inoperable, with bulky thyroid/neck masses and/or suspicion of airway obstruction * No distant metastases, including but not limited to, brain metastases, disease below the level of the carina, pulmonary parenchyma, and hepatic or bony metastases * Superior mediastinal disease (i.e., above the level of the carina) in addition to regional neck disease is allowed provided the disease can be contained in a single radiotherapy port PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * At least 12 weeks Hematopoietic * Absolute granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 75,000/mm\^3 * Hemoglobin ≥ 8.5 g/dL Hepatic * Bilirubin ≤ 1.5 mg/dL * ALT and AST ≤ 3.5 times upper limit of normal Renal * Creatinine ≤ 1.5 mg/dL Cardiovascular * LVEF ≥ 50% by echocardiogram * EKG normal * No prior angina * No prior myocardial infarction (e.g., significant Q waves), QTc \> 450 msec, or other clinically significant abnormalities on ECG * No congestive heart failure * No uncontrolled atrial arrhythmias or clinically significant arrhythmias, including any of the following: * Conduction abnormality * Nodal junctional arrhythmias and dysrhythmias * Sinus bradycardia or tachycardia * Supraventricular arrhythmias * Atrial fibrillation or flutter * Syncope or vasovagal episodes * No significant heart wall abnormality or heart muscle damage by echocardiogram * No uncontrolled hypertension (i.e., blood pressure consistently greater than 150/100 mm Hg irrespective of medication) * Hypertension is allowed provided there is clinical documentation of controlled blood pressure for 2 months before study entry * No symptomatic peripheral vascular disease or cerebrovascular disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No uncontrolled hypokalemia or hypomagnesemia * No concurrent serious infection * No other nonmalignant uncontrolled medical illness or one whose control may be jeopardized by the complications of study therapy * No grade 2 or greater pre-existing motor or sensory peripheral neuropathy * No psychiatric disorder or other condition that would preclude study compliance * No conditions associated with QTc prolongation PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent biologic therapy * No concurrent immunotherapy Chemotherapy * No prior chemotherapy * No other concurrent chemotherapy Endocrine therapy * No concurrent hormonal therapy, except for the following: * Gonadotropin-releasing hormone agonists for patients with hormone-refractory prostate cancer * Hormone replacement therapy * Oral contraceptives * Megestrol for anorexia/cachexia Radiotherapy * No prior radiotherapy * No concurrent radiotherapy Surgery * See Disease Characteristics * Prior attempt at resection or cytoreduction (e.g., debulking) surgery irrespective of surgical margins allowed provided there are no distant metastases * At least 1 week but no more than 8 weeks since prior surgery and recovered Other * No other concurrent cytotoxic therapy * No other concurrent antineoplastic therapy * No other concurrent investigational therapy * No concurrent medications known to prolong the QTc interval unless the medication can be held for at least 4 days during each treatment course


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Study Objectives
Study Objectives
Primary Objectives

Secondary Objectives


Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 3 locations
Suspended
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, United StatesSee the location
Suspended
Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer CenterCleveland, United States
Suspended
Hillman Cancer Center at University of Pittsburgh Cancer InstitutePittsburgh, United States

Suspended3 Study Centers