NCT01701349

Brief Summary

This is a multicenter, double-blind, placebo-controlled, randomized study of fosbretabulin given with chemotherapy (paclitaxel and carboplatin) compared to placebo given with chemotherapy (paclitaxel and carboplatin) in subjects with anaplastic thyroid cancer (ATC). The primary objective of the study is to determine overall survival. A maximum of 300 subjects will be recruited from approximately 75 multinational sites of which approximately 35 will be located in the United States.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Mar 2015

Typical duration for phase_3

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 2, 2012

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 5, 2012

Completed
2.4 years until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

May 1, 2014

Status Verified

April 1, 2014

Enrollment Period

2.1 years

First QC Date

October 2, 2012

Last Update Submit

April 30, 2014

Conditions

Anaplastic Thyroid Cancer

Keywords

ATCAnaplastic Thyroid CancerStage IVC Anaplastic Thyroid CancerThyroid CancerHead and Neck Tumors

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    Maximun length of study for each subject is 2 years from date of randomization

Secondary Outcomes (2)

  • Number of adverse events of the combination of fosbretabulin + paclitaxel + carboplatin

    Maximun length of study for each subject is 2 years from date of randomization

  • Number of participants with 1-year survival

    Maximun length of study for each subject is 2 years from date of randomization

Other Outcomes (1)

  • Determine the proportion of subjects with measurable disease who have objective tumor response, by treatment

    Maximun length of study for each subject is 2 years from date of randomization

Study Arms (2)

Fosbretabulin + paclitaxel + carboplatin

ACTIVE COMPARATOR

Six 21 day cycles of: Fosbretabulin (60 mg/m2) IV on Day 1, 8, 15 Paclitaxel (200 mg/m2) IV on Day 2 Carboplatin (AUC 6) IV on Day 2

Drug: Fosbretabulin + paclitaxel + carboplatin

Placebo + paclitaxel + carboplatin

PLACEBO COMPARATOR

Six 21-day cycles of: Placebo (formulated and packages to match fosbretabulin)on Day 1, 8, 15 Paclitaxel (200 mg/m2) IV on Day 2 Carboplatin (AUC6) IV on Day 2

Drug: Placebo + paclitaxel + carboplatin

Interventions

Fosbretabulin + paclitaxel + carboplatinDRUG

Fosbretabulin 200 mg/m2 IV infusion

Also known as: Fosbretabulin, Combretastatin, Zybrestat, CA4P
Fosbretabulin + paclitaxel + carboplatin
Placebo + paclitaxel + carboplatinDRUG

Paclitaxel 200 mg/m2, Carboplatin AUC 6 IV infusion

Also known as: Paclitaxel, Carboplatin
Placebo + paclitaxel + carboplatin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Unresectable, residual, recurrent or persistent ATC, histologically or cytologically confirmed
  • Prior cytotoxic therapeutic regimen as primary therapy for curative intent or prior targeted therapies (TKIs) are eligible (Prior taxane or platinum therapy is allowed)
  • Untreated ATC following biopsy, surgery for curative intent, palliation, or after radiation therapy has been considered or administered with or without radiosensitizing chemotherapy
  • Disease present on clinical exam (measurable or non-measurable)
  • Distant metastases (Stage IVC) only must have histologic confirmation of ATC either from the original primary lesion or a metastatic site
  • Neoadjuvant therapy with radiation and either radiosensitizing chemotherapy followed by surgery for curative intent, palliation, or biopsy are eligible if residual or persistent ATC is present
  • Subjects with tracheostomy are eligible
  • ECOG PS 2 or less
  • Adequate bone marrow, renal, and hepatic function, electrolytes WNL for the institution

You may not qualify if:

  • Disease that is able to be completely resected with negative microscopic margins and without any residual disease in the body
  • Active brain metastases, including symptomatic involvement, evidence of cerebral edema by prior CT or MRI, radiographic evidence of brain metastasis since definitive therapy, or continued requirement for corticosteroids for cerebral edema
  • History of malignancies other than ACT except prior lower grade thyroid malignancy, curatively treated basal cell carcinoma and in-situ melanoma of the skin, cervical intra-epithelial neoplasia,localized prostate cancer, in-situ carcinoma of the breast
  • Known intolerance or hypersensitivity to fosbretabulin, paclitaxel, carboplatin or any of their components
  • Receiving concurrent investigational therapy or have received investigational therapy for any indication within 28 days of the first scheduled day of dosing
  • Grade 3 or greater peripheral neuropathy
  • History of prior cerebrovascular event,including transient ischemic attack within the past 6 months
  • Uncontrolled hypertension defined as blood pressure \>150/100 mm Hg despite medication
  • Symptomatic vascular disease (e.g. intermittent claudication)
  • History of unstable angina pectoris pattern, myocardial infarction (including non-Q wave) within the past 6 months, or NYHA Class III or IV congestive heart failure
  • History of torsade de pointes, ventricular tachycardia, ventricular fibrillation or congenital long QT syndrome.
  • Pathologic bradycardia (\<60 b/m or heart block(excluding 1st degree block, consisting of PR interval prolongation only)
  • ECG findings of clinically significant ventricular arrhythmia, new ST segment elevation or depression, or new Q wave on ECG (PVCs are not excluded).
  • QTc interval 480 ms or more
  • Requirement of concurrent treatment with any drugs know to prolong the QTc interval, including anti-arrhythmic medications
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Conditions

Thyroid Carcinoma, AnaplasticThyroid NeoplasmsHead and Neck Neoplasms

Interventions

fosbretabulinPaclitaxelCarboplatincombretastatin

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteEndocrine System DiseasesThyroid Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesCoordination Complexes

Study Officials

  • Marcia Brose, MD, PhD

    University of Pennsylvania, Philadelphia, PA 19104

    PRINCIPAL INVESTIGATOR

  • Julie A Sosa, MD

    Yale University, New Haven, CT 06520

    PRINCIPAL INVESTIGATOR

  • Lisa Licitra, MD

    Instituto Nazionale Per Lo Studio E La Cura Dei Tumori, Milan, Italy

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 2, 2012

First Posted

October 5, 2012

Study Start

March 1, 2015

Primary Completion

April 1, 2017

Study Completion

December 1, 2017

Last Updated

May 1, 2014

Record last verified: 2014-04