Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Genistein

Tubulin Modulators

Antimitotic Agents

Protective Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Phytoestrogens

Estrogens

Hormones

Hormone Antagonists

Ascending dose evaluation of BIO 300 Oral Suspension (3 dose levels) given in combination with paclitaxel/carboplatin and radiotherapy.

Cohort 1: BIO 300 500 mg Cohort 2: BIO 300 1,000 mg Cohort 3: BIO 300 1,500 mg Cohort 4: BIO 300 Optimal dose (TBD) BIO 300 dose will be given daily, 7 days/week (Week 1, day 1 through week 6) The 2nd and 3rd dosing cohort (1,000 and 1,500 mg/day) will begin following the accrual of a minimum of 6 subjects at the previous dose level, dose escalation to the next BIO 300 dose level will be allowed to occur when a cohort has completed concurrent chemoradiotherapy with fewer than 33% Dose Limiting Toxicities (DLTs) attributed to BIO 300 Oral Suspension.

BIO 300 Oral Suspension

During the Concurrent Therapy period, paclitaxel 45 mg/m2 will be administered by intravenous drip weekly during weeks 1-6.

During the Consolidation Therapy period, paclitaxel 200 mg/m2 will be administered by intravenous drip two times, 21 days apart.

During the Concurrent Therapy period, area under the curve (AUC) = 2mg\* min/mL will be administered by intravenous drip weekly during weeks 1-6.

During the Consolidation Therapy period, carboplatin AUC = 6mg\*min/mL will be administered by intravenous drip two times, 21 days apart.

Radiation treatment will be scheduled at the discretion of the investigator provided the subject has completed a minimum of 2 days of BIO 300 dosing. Subjects will receive radiation therapy 5 days per week, once daily fractions, 1.8-2.0 Gy per fraction, for 6-7 weeks.

Radiotherapy

Michael D. Kaytor, PhD

The purpose of this study is to determine the safety and effectiveness of BIO 300 Oral Suspension when used in combination with standard dose radiation therapy and chemotherapy in patients with non-small cell lung cancer. Based on preclinical data the investigators hypothesize that BIO 300 Oral Suspension will reduce the incidence of radiation-induced pneumonitis and pulmonary fibrosis.

This is an open-label, single-arm, ascending dose Phase I/II study of BIO 300 Oral Suspension given in combination with paclitaxel/carboplatin and radiotherapy in subjects with stage II, III, or IV NSCLC who are candidates for combined chemoradiotherapy.

A minimum of 6 subjects will be accrued sequentially at each dose level of BIO 300. BIO 300 will be administered daily for the entire course of concurrent chemoradiotherapy, a minimum of 6 weeks; in combination with standard paclitaxel / carboplatin chemotherapy and radiotherapy.

The initial dose of BIO 300 will be administered on Day 1, Visit 2 in which safety data (adverse events, electrocardiograms (ECGs), results of safety laboratory determinations), pharmacokinetic (PK) and pharmacodynamic (PD) data will be collected. PK data will be collected from a minimum of six (6) study subjects from each cohort. PD data will be collected from all subjects in each study cohort. Day 1 of chemotherapy will be scheduled at the discretion of the investigator provided the subject has completed a minimum of 1 day of BIO 300 dosing. BIO 300 will be administered in combination with the chemotherapy components of the protocol (paclitaxel and carboplatin). During the first or second chemotherapy infusion, additional safety, PK and PD data will be collected. Day 1 of radiation therapy (RT) may be scheduled at the discretion of the investigator provided the subject has completed a minimum of 2 days of BIO 300 dosing. BIO 300 will continue to be administered daily; paclitaxel and carboplatin will be administered weekly and radiotherapy will be administered daily until a total dose of 60-70 Gy has been administered. During the period of combined BIO 300 and chemoradiotherapy (6-7 weeks), additional safety, PK and PD data will be collected weekly. An interim data analysis will be completed once the highest dose cohort concludes chemoradiation therapy, in an effort to determine the optimal biological dose. Following analysis, there will be an option to enroll up to an additional 12 subjects at the optimal biological dose. At the conclusion of the study, primary and secondary outcome measures will be evaluated. Data will be analyzed from all cohorts to determine the oncologic response, safety of BIO 300, and a recommended BIO 300 dose.

BIO 300 Non-Small Cell Lung Cancer Study

A Phase I/II Clinical Study Evaluating the Safety and Effectiveness of BIO 300 Oral Suspension in Patients Receiving Chemoradiation Therapy for Non-Small Cell Lung Cancer (NSCLC)

Adverse events of CTCAE v4.0 grade 3 or higher that were possibly, probably or definitely related to BIO 300 Oral Suspension and have occurred before or during concurrent chemoradiotherapy were considered dose limiting toxicities.

Measuring change from baseline (screening visit) of TGF-beta isoform 1 (TGFB1)

Best Response Rate reported per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by chest CT imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Tumor diameter was measured in centimeters. Mean change in tumor diameter from the baseline measurement at screening is reported.

The Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) questionnaire is a 36-item self-reporting instrument that measures quality of life specific to patients with cancer. Items are rated on a 5 item (point) Likert Scale, from 0 (not at all) to 4 (very much). Total scores range from 0 to 136 and higher scores indicate better quality of life. The FACT-L TOI questionnaire was scored according to FACT-L Scoring Guidelines Version 4.

The UCSD-SOBQ is a 24-item patient self-reported questionnaire where items are scored on a 6-point scale (0, "not at all" to 5, "maximal or unable to-do because of breathlessness"). Total scores range from 0 to 120 and lower scores indicate better quality of life.

The assessment will provide a score (the swallowing questionnaire) from 0 to 5; 1 no problems swallowing; 2 mild soreness only; 3 some difficulty swallowing solids; 4 cannot swallow solids; and 5 cannot swallow liquids.

Serum trough levels of paclitaxel and carboplatin were measured. Carboplatin trough levels were below the limit of quantification at all timepoints and are therefore reported as NA (Not Available).

National Cancer Institute (NCI)

Henry Ford Health System

Medical College of Wisconsin

University of Maryland, Baltimore

Milwaukee VA Medical Center

Humanetics Corporation

The CTCAE Version 4.03 was used to grade all AEs. All reported terms and descriptions for AEs were coded using CTCAE Version 4.03.

BIO 300 Oral Suspension (500 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7).

BIO 300 Oral Suspension (500 mg/Day)

BIO 300 Oral Suspension (1000 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7).

BIO 300 Oral Suspension (1000 mg/Day)

BIO 300 Oral Suspension (1500 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7).

BIO 300 Oral Suspension (1500 mg/Day)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Stage II

Stage III

Stage IV

Tumors were staged using the American Joint Committee on Cancer (AJCC) TNM system. The lower the lung cancer stage, the less the cancer has spread and the better the prognosis.

Initial Tumor Stage

Tumor Histology

Primary Tumor Location

Michael D. Kaytor

Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity

Number of Participants With Adverse Events Throughout the Study

Only participants that had blood draws for pharmacokinetics were analyzed

Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy

Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy

Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin

Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin

Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300

Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300

Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300

Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

After consolidation therapy

3 months post-RT

6 months post-RT

Analysis population only includes subjects that had a baseline measurement during the screening visit

Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1)

Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria

Visit 20

3 Months Post-RT

6 Months Post-RT

9 Months Post-RT

11 Months Post-RT

13 Months Post-RT

Number of participants vary based on the number of subjects that completed a CT scan each timepoint

Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan

Baseline

13 months post-RT

Number of participants varies based on the number of study subjects that received each assessment

DLCO as Measured by Pulmonary Function Test (PFT)

Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT)

Screening

Number of participants at each time point vary based on the number of study participants that completed the assessment

Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire.

Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire.

Weeks 1-6 Average

Extent of Esophagitis by Patient Reported Swallowing Diary

Number of participants analyzed at each time point varies based on the number of subjects available for pharmacokinetic blood draw

Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300

All subjects receiving concurrent paclitaxel chemoradiotherapy

All subjects receiving concurrent carboplatin chemoradiotherapy

Number of participants at each time point varies based on the number of participants with blood sample available for analysis.

Spots Global Cancer Trial Database for bio 300 oral suspension