Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Number of Participants With an Objective Response (Complete Response + Partial Response)
Study Overview
Brief Summary
Background:
- Mithramycin is a drug that was first tested as a cancer therapy in the 1960s. It acted against some forms of cancer, but was never accepted as a treatment. Research suggests that it may be useful against some cancers of the chest, such as lung and esophageal cancer or mesothelioma. Researchers want to see if mithramycin can be used to treat these types of cancer.
Objectives:
- To see if mithramycin is safe and effective against different chest cancers.
Eligibility:
- Individuals at least 18 years of age who have lung, esophagus, pleura, or mediastinum cancers.
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor tissue samples will be used to monitor the cancer before treatment.
- Participants will receive mithramycin every day for 7 days, followed by 7 days without treatment. Each 14-day round of treatment is called a cycle.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Participants will continue to take the drug for as long as the side effects are not severe and the tumor responds to treatment.
Detailed Description
Background:
Increasing evidence indicates that activation of stem cell gene expression is a common mechanism by which environmental carcinogens mediate initiation and progression of thoracic malignancies. Similar mechanisms appear to contribute to extra-thoracic malignancies that metastasize to the chest. Utilization of pharmacologic agents, which target gene regulatory networks mediating stemness may be novel strategies for treatment of these neoplasms. Recent studies performed in the Thoracic Epigenetics Laboratory, Thoracic and Oncology Surgery Branch (TOSB)/National Cancer Institute (NCI), demonstrate that under exposure conditions potentially achievable in clinical settings, mithramycin diminishes stem cell gene expression and markedly inhibits growth of lung and esophageal cancer and malignant pleural mesothelioma (MPM) cells in vitro and in vivo. These finding add to other recent preclinical studies demonstrating impressive anti-tumor activity of mithramycin in epithelial malignancies and sarcomas that frequently metastasize to the thorax.
Primary Objective:
-To assess clinical response rates of mithramycin administered as 6 hour intravenous infusions in patients with malignancies involving lungs, esophagus, pleura, or mediastinum.
Eligibility:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1/mithramycin
Single agent intravenous (IV) mithramycin
Intervention: Mithramycin (Drug)
Outcomes
Primary Outcomes
Number of Participants With an Objective Response (Complete Response + Partial Response)
Time Frame: Every 8 weeks until disease progression or unacceptable toxicity, over an average of 4 months.
Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesion, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Secondary Outcomes
- Number of Participants With Serious and Non-Serious Adverse Events(Date treatment consent signed to date off study, approx. 9 mos & 6 days DL1 30 mcg/kg thoracic group, 2 mos & 16 days DL1 30 mcg/kg extra-thoracic group, 5 mos & 26 days DL-1 25 mcg/kg thoracic group, & 20 days DL-1 25 mcg/kg extra-thoracic group)
Investigators
David Schrump, M.D.
Principal Investigator
National Cancer Institute (NCI)