High Dose Vitamin A Compound in Treating Participants With Resectable Non-Small Cell Lung Cancer

A Pilot Study of Neoadjuvant High Dose Vitamin A for Resectable Non-Small Cell Lung Cancer

This trial studies how well high dose vitamin A compound works in treating participants with non-small cell lung cancer that can be removed by surgery. Vitamin A compound may increase the number of germinal centers (immune centers that make antibodies mature) in tumor and lymph tissues which may be beneficial to patients with cancer.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer; Stage Ib Lung Carcinoma; Stage IIA Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage I Lung Cancer; Stage IA Lung Carcinoma AJCC V7
• Intervention / Treatment: Drug: Vitamin A Compound; Procedure: Therapeutic Conventional Surgery

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the percentage of resected cancers containing germinal centers (GCs) in patients who receive neoadjuvant vitamin A compound (vitamin A) to controls.

SECONDARY OBJECTIVES:

I. To compare the abundance of GCs in adjacent lymph nodes in patients who receive neoadjuvant vitamin A to controls.

II. To compare histopathologic responses based on tumor necrosis in lung cancer patients who receive neoadjuvant vitamin A to controls.

III. To compare overall survival of patients who receive neoadjuvant vitamin A to controls.

EXPLORATORY OBJECTIVES:

I. To describe immunophenotypic changes of monocytes including myeloid derived suppressor cells (MDSCs) in pre- and post-treatment blood samples.

OUTLINE: Participants are randomized to 1 of 2 groups.

GROUP I: Participants receive vitamin A compound orally (PO) for 7 consecutive days in the absence of disease progression or unacceptable toxicity. Within 21 days of completing treatment, participants then undergo surgical resection.

GROUP II: Participants undergo surgical resection.

After completion of study treatment, participants are followed up for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient must be 18 years of age or older.
• Patients must have either biopsy proven or radiographically suspected non-small cell lung cancer.
• Patients must have disease in the chest that is felt to be surgically resectable.
• ECOG performance status of 0-2.
• Ability to understand and the willingness to sign an IRB-approved informed consent document

Exclusion Criteria:

• Patients younger than 18 years of age
• Women who are pregnant or breast feeding.
• Patients may not be receiving any other investigational agents for the treatment of nonsmall cell lung cancer.
• Patients may not be taking the following medications: high dose vitamin A supplement (multivitamin supplements prohibited only if vitamin A content is greater than 3,500 international units), bexarotene, alitretinoin, tretinoin, adapalene, isotretinoin, acitretin, doxycycline, minocycline, or demeclocycline,
• Uncontrolled intercurrent illness including, but not limited to, pancreatitis, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Hypervitaminosis A - toxic effects of ingesting too much vitamin A.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin A compound; Participants receive vitamin A compound PO for 7 consecutive days in the absence of disease progression or unacceptable toxicity. Within 21 days of completing treatment, participants then undergo surgical resection.	Drug: Vitamin A Compound; Participants randomized to this arm will receive 7 consecutive days of of Vitamin A compound without disease progression or unacceptable toxicities. Within 21 days of completion of treatment participants will undergo surgical resection; Other Names: Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraen-1-ol, 68-26-8, A 313, Anti-Infective Vitamin, Anti-Infective vitamin, Antixerophthalmic Vitamin, Antixerophthalmic vitamin
Active Comparator: Therapeutic Conventional Surgery; Description Participants undergo surgical resection.	Procedure: Therapeutic Conventional Surgery; Participants randomized to this arm will receive surgical resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or Absence of Germinal Centers in Resected Tissue	Presence/absence of germinal centers (GCs) in resected cancer tissues from patients who receive neoadjuvant vitamin A and controls.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Germinal Centers in Lymph Nodes	Measurement of GCs per unit area in adjacent lymph nodes will be assessed using semi-quantitative designation (Score of high, moderate, low, or absent) in patients who receive neoadjuvant vitamin A and controls.	Up to 2 years
Presence or Absence of Tumor Necrosis	Pathologic response will be defined by tumor necrosis which will be dichotomized as present or absent in patients who receive neoadjuvant vitamin A and controls	Up to 2 years
Overall Survival	Overall survival of patients receiving neoadjuvant Vitamin A and in controls.	Up to 2 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: William J Petty, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Actual): December 9, 2022
• Study Completion (Actual): December 9, 2022

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Antioxidants; Anticarcinogenic Agents; Vitamins; Anti-Infective Agents; Vitamin A; Retinol palmitate
• Other Study ID Numbers: IRB00050640 (Wake Forest Baptist Comprehensive Cancer Center); P30CA012197 (U.S. NIH Grant/Contract); WFBCCC 62218 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center); NCI-2018-00888 (Other Identifier: Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No