BIO 300 Non-Small Cell Lung Cancer Study (NSCLC)

• ClinicalTrials.gov Identifier: NCT02567799
• Recruitment Status: Completed
• First Posted: October 5, 2015
• Last Update Posted: November 25, 2020
• Sponsor: Humanetics Corporation
• Collaborators: National Cancer Institute (NCI); Henry Ford Health System; Medical College of Wisconsin; University of Maryland, Baltimore; Milwaukee VA Medical Center
• Information provided by (Responsible Party): Humanetics Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: BIO 300 Oral Suspension; Drug: Paclitaxel; Drug: Carboplatin; Radiation: Radiotherapy	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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)
• Study Start Date: November 2015
• Actual Primary Completion Date: April 2019
• Actual Study Completion Date: September 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Single-arm; Ascending dose evaluation of BIO 300 Oral Suspension (3 dose levels) given in combination with paclitaxel/carboplatin and radiotherapy.

Drug: BIO 300 Oral Suspension; 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.; Other Name: genistein, 5, 7-dihydroxy-3-(4-hydroxyphenyl)-chromen-4-one; Drug: Paclitaxel; 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.; Other Names: Onxol; Taxol; Drug: Carboplatin; 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.; Other Names: Paraplatin; CARBOplatin Novaplus; Radiation: Radiotherapy; 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.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events that meet the protocol defined criteria of a Dose Limiting Toxicity while receiving BIO 300 in combination with chemoradiotherapy [ Time Frame: Day 1 up to 6 weeks or maximum tolerated dose ]

Secondary Outcome Measures :

1. Number of participants with adverse events throughout the study [ Time Frame: Day 1 up to month 13 post radiation or 12 months post chemotherapy consolidation for surgical participants. ]
2. Maximum Serum Concentration (Cmax) of BIO 300 administered in the absence of chemotherapy [ Time Frame: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose ]
3. Area Under the Serum Concentration Curve (AUC) of BIO 300 administered in the absence of chemotherapy [ Time Frame: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose ]
4. Maximum Serum Concentration (Cmax) of BIO 300 when administered in combination with paclitaxel and carboplatin [ Time Frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose ]
5. Area Under the Serum Concentration Curve (AUC) of BIO 300 when administered in combination with paclitaxel and carboplatin [ Time Frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose ]
6. Maximum Serum Concentration (Cmax) of paclitaxel when administered in combination with BIO 300 [ Time Frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose ]
7. Area Under the Serum Concentration Curve (AUC) of paclitaxel when administered in combination with BIO 300 [ Time Frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose ]
8. Maximum Serum Concentration (Cmax) of carboplatin when administered in combination with BIO 300 [ Time Frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose ]
9. Area Under the Serum Concentration Curve (AUC) of carboplatin when administered in combination with BIO 300 [ Time Frame: Week1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose ]
10. Expression levels of serum-derived pharmacodynamic markers [ Time Frame: Day 1, just prior to BIO 300 dose and 3 hours after admin., week 1 or 2, during 1st or 2nd chemotherapy infusion, just prior to BIO 300 dose and 3 hours after admin., weekly during weeks 2, 3, 4, 5, & 6 prior to BIO 300, paclitaxel, and carboplatin dose ]
11. Rate of progressive disease evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) criteria [ Time Frame: Screening, visits 20, 37, 38, 39, 40, 41 & 42 (through visit 41 for surgical participants) ]
12. Extent of disease as measured by diagnostic Computerized Tomography (CT) Scan [ Time Frame: Screening, visits 20 and 3, 6, & 11 months post radiation therapy for non-surgical participants; screening, visits 20, S (surgical assessment visit), & 37 and 3, 6, 9 and 12 months post consolidation for surgical participants ]
13. Extent of disease as measured by Pulmonary Function Test (PFT) [ Time Frame: Screening and months 6 & 13 post radiation therapy for non-surgical participants; screening & visit S and 6 & 13 months post consolidation for surgical participants ]
14. Incidence of pulmonary fibrosis assessed by four-dimensional computerized tomography (4D-CT) [ Time Frame: Screening, visits 20 & 37 and 9 & 13 months post radiation therapy for non-surgical participants; screening only for surgical participants ]
15. Quality of Life (QOL) as measured by Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) patient reported outcome questionnaire. [ Time Frame: Screening and months 3, 6, & 13 post radiation therapy for non-surgical participants; screening and months 3, 6, & 12 post consolidation for surgical participants ]
16. Quality of Life (QOL) as measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOB) patient reported outcome questionnaire. [ Time Frame: Screening and months 3, 6, & 13 post radiation therapy for non-surgical participants; screening and months 3, 6, & 12 post consolidation for surgical participants ]
17. Extent of esophagitis by patient reported Swallowing Diary [ Time Frame: Screening, weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post radiation therapy for non-surgical participants; screening, weekly weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post consolidation for surgical participants ]
18. Weekly BIO 300 trough levels, serum concentration of BIO 300 [ Time Frame: Days 1 & 2 and weeks 2, 3, 4, 5, & 6 prior to daily BIO 300 dose ]
19. Weekly paclitaxel trough levels, plasma concentration of paclitaxel [ Time Frame: Day 2 and weeks 2, 3, 4, 5, & 6 prior to daily BIO 300 dose & paclitaxel infusion ]
20. Weekly carboplatin trough levels, plasma concentration of carboplatin [ Time Frame: Day 2 and weeks 2, 3, 4, 5, & 6 prior to daily BIO 300 dose & carboplatin infusion ]
21. Pathological response of target lesions [ Time Frame: Post operatively between day 59 and day 66 ]
22. Extent of surgical resection [ Time Frame: Post operatively between day 59 and day 66 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histological or cytological confirmation of NSCLC
2. Stage II, III, or IV NSCLC for whom radiation therapy of 60 Gy and concurrent weekly paclitaxel/carboplatin is recommended
3. Up to three small (≤ 3 cm each) lung oligometastases will be allowed and/or one oligometastasis at any other site in the body
4. Eastern Cooperative Oncology Group Performance Scale (ECOG PS) of 0 or 1
5. Forced expiratory volume at one second (FEV1): best value obtained pre- or post-bronchodilator must be ≥ 1.0 liters/second or > 50% predicted value
6. Adequate bone marrow reserve
7. Adequate hepatic reserve
8. Adequate renal function
9. Female subjects of childbearing potential must have a negative pregnancy test
10. Female subjects of childbearing potential and male subjects with female sexual partners of childbearing potential must agree to use an effective method of contraception
11. Ability to read and provide written informed consent

Exclusion Criteria:

1. Weight loss greater than 10% in prior 4 weeks
2. Prior malignancy in which they received any thoracic radiotherapy unless the treating physician considers it unlikely to impact the clinical outcome of the patient
3. Patients with concurrent invasive malignancy other than non-melanoma skin cancer or cervical intraepithelial neoplasia unless the treating physician considers it unlikely to impact the clinical outcome of the patient
4. An active infection or with a fever ≥ 38.5°C
5. Poorly controlled intercurrent illnesses
6. Patients with a prior thoracotomy within 1 week of study registration
7. Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration

8. Patients with any of the following are not eligible:

   • Previous history of Corrected QT Interval (QTc ) prolongation resulting from medication that required discontinuation of that medication
   • Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age;
   • Presence of left bundle branch block (LBBB);
   • QTc with Fridericia's correction that is unmeasurable, or ≥ 480 msec on screening ECG. The average QTc from the screening ECG (completed in triplicate) must be < 480 msec in order for the patient to be eligible for the study;
   • Subjects taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes are not eligible if QTc ≥ 460 msec.
9. Patients must not have had a clinically significant cardiac event within 6 months before entry; or the presence of any other uncontrolled cardiovascular conditions that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
10. Patients with a history of arrhythmia or asymptomatic sustained ventricular tachycardia are not eligible. Patients with atrial fibrillation with well-controlled ventricular rate on medication, are eligible.
11. Psychiatric conditions, social situations or substance abuse that precludes the ability of the subject to cooperate with the requirements of the trial and protocol therapy
12. Grade 2 or higher peripheral neuropathy
13. Known history of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS), hepatitis B or C.
14. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
15. Women who are breastfeeding are not eligible for this study.

Contacts and Locations

Locations

United States, Maryland

University of Maryland School of Medicine

Baltimore, Maryland, United States, 21201

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202-2689

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Zablocki VA Medical Center

Milwaukee, Wisconsin, United States, 53295

Sponsors and Collaborators

Humanetics Corporation

National Cancer Institute (NCI)

Henry Ford Health System

Medical College of Wisconsin

University of Maryland, Baltimore

Milwaukee VA Medical Center

Investigators

• Study Director: Michael D. Kaytor, PhD; Humanetics Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Citrin DE, Prasanna PGS, Walker AJ, Freeman ML, Eke I, Barcellos-Hoff MH, Arankalayil MJ, Cohen EP, Wilkins RC, Ahmed MM, Anscher MS, Movsas B, Buchsbaum JC, Mendonca MS, Wynn TA, Coleman CN. Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016. Radiat Res. 2017 Jul;188(1):1-20. doi: 10.1667/RR14784.1. Epub 2017 May 10.

• Responsible Party: Humanetics Corporation
• ClinicalTrials.gov Identifier: NCT02567799
• Other Study ID Numbers: CL0101-01; HHSN261201200078C ( Other Grant/Funding Number: NCI )
• First Posted: October 5, 2015
• Last Update Posted: November 25, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Humanetics Corporation:

Lung Neoplasms

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Paclitaxel; Carboplatin; Genistein; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors; Phytoestrogens; Estrogens, Non-Steroidal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists