Study of Combretastatin and Paclitaxel/Carboplatin in the Treatment of Anaplastic Thyroid Cancer

NCT00507429 | Terminated Phase 2 Results DMC

• 1 other identifier: OXC4T4-302
• Study Type: interventional
• Target: 80
• Locations: 12 countries
• Sites: 41

Brief Summary

The purpose of the study is to determine the safety and efficacy of combretastatin combined with paclitaxel and carboplatin in the treatment of anaplastic thyroid cancer (ATC).

Conditions

Anaplastic Thyroid Cancer

Keywords

thyroid neoplasms; thyroid cancer; thyroid carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  From randomization to date last known alive

Secondary Outcomes (2)

• To Determine Progression Free Survival

  from randomization through end of study visit

• To Determine Percentage of 1 Year Survival

  from randomization through end of study visit

Study Arms (2)

Arm 1: CA4P + Carboplatin + paclitaxel

EXPERIMENTAL

Six 21-day cycles: CA4P (60 mg/m2 on Days 1, 8, 15), carboplatin (AUC 6) + paclitaxel (200 mg/m2) on Day 2

Drug: CA4P

Arm 2: Carboplatin + Paclitaxel

ACTIVE COMPARATOR

Six 21-day cycles of Carboplatin (AUC 6) + paclitaxel (200 mg/m2) given on Day 1

Drug: paclitaxel; Drug: carboplatin

Interventions

CA4P DRUG

CA4P 60mg/m squared for Days 1, 8, 15 for 6 cycles

Also known as: combretastatin, fosbretabulin, Zybrestat

Arm 1: CA4P + Carboplatin + paclitaxel

paclitaxel DRUG

200mg/m squared on Day 1

Also known as: Taxol, Paxene

Arm 2: Carboplatin + Paclitaxel

carboplatin DRUG

6 AUC on Day 1 following paclitaxel

Also known as: Paraplatin

Arm 2: Carboplatin + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Anaplastic thyroid carcinoma histologically or cytologically confirmed by a pathology review
• Refractory to or progressed during or after therapy, or relapsed within 6 months following initial combined modality therapy (usually including systemic chemotherapy and radiation) for regionally advanced disease
• Systemic therapy is limited to one chemotherapy regimen that is clearly administered contiguously, (i.e., in an uninterrupted primary therapeutic approach)
• Prior radiation: 3 weeks must have elapsed since radiation and disease must be present beyond radiation ports
• Minimum of 3 weeks must have elapsed from the time of last chemotherapy prior to the first dose of study drug
• Patients with bulky thyroid/neck masses and/or suspicion of airway obstruction must undergo screening (indirect and direct laryngoscopy) to ensure patency of the trachea/airway prior to study enrollment and treatment
• ECOG Performance Score less than or equal to 2
• Adequate bone marrow reserve as evidenced by absolute neutrophil count (ANC) greater than 1,500/microL, platelet count greater than 75,000/microL.
• Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (less than 177 micromol/L)
• Adequate hepatic function as evidenced by serum total bilirubin less than 2X greater than the upper limit of normal (ULN) (less than3X ULN in patients with liver metastases), AST (aspartate aminotransferase)/ALT (alanine aminotransferase) less than or equal to 3X the ULN for the local reference lab (less than or equal to 5X the ULN for patients with liver metastases)
• No clinically important sequelae from any prior surgery or radiotherapy.

You may not qualify if:

• Tumors confined to the thyroid.
• Clinically evident brain metastasis, including symptomatic involvement, evidence of cerebral edema by CT or MRI, radiographic evidence of progression of brain metastasis since definitive therapy, or continued requirement for corticosteroids
• Patients who receive chemotherapy for metastatic disease after completion of a combined modality approach.
• History of malignancies other than ATC except curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of less than 4.0 mg/dL or microg/L
• Known hypersensitivity to CA4P, paclitaxel or carboplatin, or any of their components
• Receiving concurrent investigational therapy or who have received investigational therapy for any indication within 28 days of the first scheduled day of dosing
• Greater than Grade 2 peripheral neuropathy
• History of prior cerebrovascular event, including transient ischemic attack
• Uncontrolled hypertension (blood pressure greater than 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 MI) within the past 6 months, or NYHA Class III and IV congestive heart failure
• History of torsade de pointes
• Bradycardia (less than 60 b/m), heart block (excluding 1st degree block, being PR interval prolongation only), and congenital long QT syndrome
• Any ventricular arrhythmias, or new ST segment elevation or depression or Q wave on ECG
• Ejection fractions less than normal (i.e. less than 45%)

Sponsors & Collaborators

• Mateon Therapeutics: lead

Study Sites (41)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale University, School of Medicine

New Haven, Connecticut, 06520, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Sidney Kimmel Comprehensive Cancer Care Center at John Hopkins

Baltimore, Maryland, 21231, United States

Location

University of Minnesota Otolaryngology Department

Minneapolis, Minnesota, 55455, United States

Location

Ireland Cancer Center/Division od Hematology

Cleveland, Ohio, 44106, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Belarus National Medical University

Minsk, Belarus

Location

Regional Oncology Dispensary with Inpatient Sector

Plodiv, Bulgaria

Location

Specialized Hospital for Active Treatment of Oncology

Sofia, 1504, Bulgaria

Location

Universtiy Multiprofile Hospital, ISUI, Clinic of Oncotherapy

Sofia, Bulgaria

Location

University Hospital, Cairo

Cairo, Egypt

Location

Mediciti Hospital

Hyderabaad, Andhra Pradesh, 500063, India

Location

Kidwai Memorial Hospital

Bangalore, Karnataka, India

Location

Shirdi Sai Baba Cancer Hospital

Manipal, Karnataka, 576119, India

Location

Tata Memorial Centre

Mumbai, Maharashtra, 400012, India

Location

Ruby Hall Clinic

Pune, Maharashtra, 411011, India

Location

All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, 110029, India

Location

Apollo Cancer Institute

New Delhi, National Capital Territory of Delhi, 110076, India

Location

Christian Medial College

Vellore, Tamil Nadu, India

Location

Telaviv Sourasky Medical Center, Head and Neck Service Division of Oncology

Tel Aviv, 64239, Israel

Location

Lo Studio E la Cura

Milan, 20133, Italy

Location

INT Napoli Fondazione Pascale

Napoli, Italy

Location

Istituto Oncologico Veneto (IOV) - IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero - Universitaria Pisana

Pisa, 56124, Italy

Location

Zaklad Medyczny Nuklearnej i Endykrynologii

Gliwice, 44-101, Poland

Location

Klinika Nowotworow Glowy i Szyji

Warsaw, 02-781, Poland

Location

Institutul Oncologic

Cluj-Napoca, 400015, Romania

Location

SC Meditech SRL

Craiova, 200535, Romania

Location

Centr of Medical Oncology

Iași, 700106, Romania

Location

Clinical County Hospital Sibiu

Sibiu, 550245, Romania

Location

Emergency Clinical County Hospital "Sf. loan cel Nou"

Suceava, 720237, Romania

Location

City Clinical Oncology Dispensary

Saint Petersburg, 198255, Russia

Location

Ukrainian Academy of Medical Science

Lomonosova 33/43, Kiev, 03022, Ukraine

Location

Regional Clinical Oncology Dispensary

Lviv, Ukraine

Location

Beatson Oncology Centre, Gartnavel General Hospital

Glasgow, Scotland, G12 OYN, United Kingdom

Location

Royal Marsden Hospital and Institute of Cancer Research

London, SW3 6JJ, United Kingdom

Location

Southampton Hospital Oncology Centre

Southampton, United Kingdom

Location

Related Publications (8)

• Yeung SC, She M, Yang H, Pan J, Sun L, Chaplin D. Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is effective against anaplastic thyroid cancer in a nude mouse xenograft model. J Clin Endocrinol Metab. 2007 Aug;92(8):2902-9. doi: 10.1210/jc.2007-0027. Epub 2007 Jun 5.

  PMID: 17550961 BACKGROUND

• Patel KN, Shaha AR. Poorly differentiated and anaplastic thyroid cancer. Cancer Control. 2006 Apr;13(2):119-28. doi: 10.1177/107327480601300206.

  PMID: 16735986 BACKGROUND

• Ain KB. Anaplastic thyroid carcinoma: behavior, biology, and therapeutic approaches. Thyroid. 1998 Aug;8(8):715-26. doi: 10.1089/thy.1998.8.715.

  PMID: 9737368 BACKGROUND

• De Crevoisier R, Baudin E, Bachelot A, Leboulleux S, Travagli JP, Caillou B, Schlumberger M. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1137-43. doi: 10.1016/j.ijrobp.2004.05.032.

  PMID: 15519785 BACKGROUND

• Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer. 2004 Jun 15;100(12):2491-9. doi: 10.1002/cncr.20299.

  PMID: 15197790 BACKGROUND

• Horsman MR, Siemann DW. Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res. 2006 Dec 15;66(24):11520-39. doi: 10.1158/0008-5472.CAN-06-2848.

  PMID: 17178843 BACKGROUND

• Cooney MM, Savvides P, Agarwala SS, Wang D, Flick S, Bergant S, Bhatka S,Fu P, Subbiah V, Lavertu P, Ortiz J, and Remick S. Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma. J Clinical Oncology, 2006 Vol. 24, 5580.

  BACKGROUND

• Giri P, Batra PJ, Kumari A, Hura N, Adhikary R, Acharya A, Guchhait SK, Panda D. Development of QTMP: A promising anticancer agent through NP-Privileged Motif-Driven structural modulation. Bioorg Med Chem. 2023 Nov 15;95:117489. doi: 10.1016/j.bmc.2023.117489. Epub 2023 Oct 5.

  PMID: 37816266 DERIVED

Related Links

• Link to Thyroid Cancer Survivors website

MeSH Terms

Conditions

Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms

Interventions

combretastatin; fosbretabulin; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Limitations and Caveats

The study was to enroll 180 subjects. Enrollment was terminated early due to low accrual rate. Eighty subjects were enrolled.

Results Point of Contact

• Title: Peter Langecker, MD, PhD
• Organization: OXiGENE, Inc.

plangecker@oxigene.com

650 635 7008

Study Officials

• Julie A. Sosa, MD, FACS

  Yale University School of Medicine, New Haven, CT

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 26, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2011
• Study Completion: November 1, 2011
• Last Updated: June 9, 2014
• Results First Posted: June 9, 2014

Record last verified: 2014-02

Locations

IN (8); BE (1); BU (3); UA (2); RO (5); RU (1); GB (3); PL (2); IT (4); US (10); IL (1); EG (1)