Gland and Hormone Related Diseases

All Conditions

Neoplasms

Rare Diseases

Thyroid Diseases

Carcinoma

Thyroid Neoplasms

Head and Neck Neoplasms

Thyroid Carcinoma, Anaplastic

Endocrine System Diseases

Endocrine Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anaplastic Thyroid Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Fosbretabulin

Combretastatin

Tubulin Modulators

Antimitotic Agents

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

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

Fosbretabulin + paclitaxel + carboplatin

Paclitaxel 200 mg/m2, Carboplatin AUC 6 IV infusion

Placebo + paclitaxel + carboplatin

Marcia Brose, MD, PhD

Julie A Sosa, MD

Lisa Licitra, MD

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.

The Treatment Plan followed for all subjects will consist of:

* A Screening Visit within 14 days before study drug (fosbretabulin or placebo) administration
* A Treatment Phase of 21-day combination treatment (study drug plus chemotherapy) cycles (up to 6 cycles)
* An End of Treatment Phase assessment
* An End of Study Visit occurring 30 days after the last day of study drug administration, as able

After the last clinic visit, all subjects will be followed for survival by monthly phone calls, email, or in-person.

Fosbretabulin or Placebo in Combination With Carboplatin/Paclitaxel in Anaplastic Thyroid Cancer

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Fosbretabulin Tromethamine (CA4P) in Combination With Paclitaxel and Carboplatin in Anaplastic Thyroid Carcinoma (FACT2)

Mateon Therapeutics

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Chemotherapy plus Multi Kinase Inhibitor: Sorafenib Group - Sorafenib (Nexavar, BAY43-9006), \[400 mg, (2 tablets x 200 mg each) orally, twice daily\] on Study Days 2-19 and paclitaxel (175 mg/m\^2, intravenous (IV), over 2.5 to 4 hours) and carboplatin (area under the curve (AUC) =5, IV for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days.

Chemotherapy + Placebo: Placebo Group - Placebo (2 tablets twice daily, orally) on Study Days 2-19 and paclitaxel (175 mg/m\^2 IV, over 2.5 to 4 hours) and carboplatin (AUC=5 IV, for 15 to 60 minutes) on Study Day 1. The cycle duration will be 21 days

Sorafenib + Paclitaxel + Carboplatin

Placebo + Paclitaxel + Carboplatin

Bayer Study Director

The purpose of this study conducted in Asia-Pacific was to evaluate the efficacy and safety of Sorafenib in combination with paclitaxel and carboplatin versus placebo in combination with paclitaxel and carboplatin for chemonaive patients with unresectable stage IIIB (with effusion) or stage IV NSCLC. However, as indicated below, the study was terminated prematurely when the results from Study 11961 (NCT00300885), an earlier Phase 3 study of similar design in subjects with advanced NSCLC, showed an overall lack of efficacy and increased mortality in subjects with squamous subtype. The data available is presented as descriptive analyses, due to the limitations of implementing the statistical analysis plan.

The study was terminated early when the results from Study 11961 (NCT00300885), an earlier Phase 3 study evaluating the effects of Sorafenib in combination with paclitaxel and carboplatin in subjects with advanced NSCLC, showed an overall lack of efficacy of Sorafenib in combination with paclitaxel and carboplatin in NSCLC and increased mortality in subjects with squamous subtype.

A Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)

Progression free survival (PFS) is the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented. Since the study was terminated early and 89% of subjects' data were censored, only the number of PFS events (Failed \[progressed or died before progression\]) is reported, not the usual measure "number of days".

Overall survival is the number of days from the date of randomization to the date of death due to any cause. Subjects alive at the time of analysis were censored at their last date of follow-up. Since the study was terminated early and 89% of subjects' data were censored, only the number of subjects who Failed (died) or were Censored is reported, not the usual measure "number of days".

Complete response (CR): Disappearance of all target lesions (TL). Partial response (PR): At least 30% decrease in sum of the largest diameter (LD) of TLs, taking baseline sum as reference. Stable disease (SD): No change in tumor size. Progressive disease (PD): At least a 20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since treatment started, or the appearance of 1 or more new lesions.

Duration of response (PR or better) was defined as the time from the first documented objective PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Since only 4 subjects had a response, the duration of response was not calculated.

The LCS is a validated instrument for determining treatment impact on lung symptoms. The LCS consists of 7 questions with 5 responses ranging from "not at all" to "very much". The LCS total score ranges from 0 to 28. Lower scores reflect greater lung cancer symptoms.

HRQoL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire, a validated instrument for determining lung cancer HRQoL. The 36-item questionnaire includes 4 domains: Physical, functional, emotional, and social/family well-being, and a lung cancer-specific subscale. The FACT-L total score ranges from 1 to 136. Lower scores demonstrate impaired HRQoL.

Bayer

The following acronyms and abbreviations were used in the Results section: Absolute Neutrophil Count (ANC); Not Otherwise Specified (NOS); Alanine aminotransferase (ALT); Gastrointestinal (GI)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Grade 0: Fully active

Grade 1: Restricted strenuous activity, ambulatory

Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead). Subjects entering this study must have had an ECOG score of 0 or 1(restricted in physically strenuous activity but ambulatory).

Eastern Cooperative Oncology Group (ECOG) performance status

China

Non-China

Subjects in the study were stratified as to whether they were from China or not from China.

Geographic region

Squamous cell (epidermoid) carcinoma

Other

Missing histology

Subjects in the study were stratified by the histology of their non-small cell lung cancer into non-squamous vs squamous.

Histology

Missing

Stage IIIB

Stage IV

Subjects in the study were stratified by the stage of their disease: Stage IIIB (with cytologically confirmed malignant pleural or pericardial effusion) or Stage IV histological or cytological confirmation of Non-Small Cell Lung Cancer (NSCLC).

Stage at study entry

Due to early termination of the study, no comparison of treatments was possible. This study also provided limited opportunity to distinguish between Adverse Events associated with sorafenib and events associated with the underlying lung disease.

Therapeutic Area Head

Failed (progressed or died before progression)

Censored

It was intended to include all randomized subjects (the intent to treat (ITT) population) in the analysis. Since 89% of subjects were censored, PFS could not be calculated. The number of subjects who Failed (progressed or died before progression) or were Censored are reported.

Progression Free Survival

Failed (died)

All randomized subjects (the intent to treat (ITT) population) were included in the analysis. Since 89% of subjects were censored, OS could not be calculated. The number of subjects who Failed (died) or were Censored are reported.

Overall Survival (OS)

Complete repsonse (CR)

Partial response (PR)

Stable disease (SD)

Progressive disease (PD)

not evaluated

All randomized subjects (the intent to treat (ITT) population) were included in the analysis.

Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)

The first subject who showed a response

The second subject who showed a response

The third subject who showed a response

The fourth subject who showed a response

All subjects that showed a response. Since only 4 subjects had a response, the data were not analyzed.

Duration of Response

Cycle 2 (N = 31 sorafenib/33 placebo)

Cycle 3 (N = 16 sorafenib/23 placebo)

Cycle 4 (N = 12 sorafenib/14 placebo)

Cycle 5 (N = 7 sorafenib/5 placebo)

Cycle 6 (N = 4 sorafenib/3 placebo)

Cycle 7 (N = 2 sorafenib/1 placebo)

Of the 91 randomized subjects in the ITT population, 90 completed the LCS at baseline. Since more than half of the subjects received only 1 or 2 cycles before the trial was stopped, the response rate (number of evaluable subjects completing the questionnaire) decreased from cycle to cycle and makes the results hard to interpret.

Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2

Cycle 3 (N = 16 sorafenib/21 placebo)

Of the 91 randomized subjects in the ITT population, 88 completed the FACT-L at baseline. Since more than half of the subjects received only 1 or 2 cycles before the trial was stopped, the number of subjects who completed the questionnaire after the first cycles was very low, making the results difficult to interpret.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fosbretabulin or Placebo in Combination With Carboplatin/Paclitaxel in Anaplastic Thyroid Cancer	NCT01701349	Anaplastic Thyr...	Fosbretabulin +... Placebo + pacli...	18 Years -	Mateon Therapeutics
Fosbretabulin or Placebo in Combination With Carboplatin/Paclitaxel in Anaplastic Thyroid Cancer	NCT01701349	Anaplastic Thyr...	Fosbretabulin +... Placebo + pacli...	18 Years -	Mateon Therapeutics
A Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)	NCT00558636	Carcinoma, Non-...	Sorafenib + Pac... Placebo + Pacli...	18 Years -	Bayer
A Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC)	NCT00558636	Carcinoma, Non-...	Sorafenib + Pac... Placebo + Pacli...	18 Years -	Bayer

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