Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Mithramycin for Lung, Esophagus, and Other Chest Cancers

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01624090
First received: June 16, 2012
Last updated: September 28, 2016
Last verified: September 2016
  Purpose

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.

Condition Intervention Phase
Lung Cancer
Esophageal Cancer
Mesothelioma
Gastrointestinal Neoplasms
Breast Cancer
Drug: Mithramycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Objective response rate [ Time Frame: Every 4 weeks until disease progression or unacceptable toxicity ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • List and description of toxicities [ Time Frame: Until 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Time Frame: 8 weeks (days 1, 2, 4, 7, 8 & 9 of the 1st 2 4 week cycles) ] [ Designated as safety issue: No ]

Estimated Enrollment: 57
Study Start Date: June 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
IV mithramycin in patients with primary lung cancer (CLOSED)
Drug: Mithramycin
30 mcg/kg IV over 6 h once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity
Experimental: 2
IV mithramycin in patients with extrathoracic cancer metastatic to the lung (CLOSED)
Drug: Mithramycin
30 mcg/kg IV over 6 h once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity
Experimental: 3
IV mithramycin in patients with primary lung cancer with favorable genotypes
Drug: Mithramycin
30 mcg/kg IV over 6 h once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity
Experimental: 4
IV mithramycin in patients with extrathoracic cancer metastatic to the lung with favorable genotypes
Drug: Mithramycin
30 mcg/kg IV over 6 h once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Diagnosis: Patients with measurable inoperable, histologically confirmed primary lung and esophageal carcinomas, thymic neoplasms, germ cell tumors, malignant pleural mesotheliomas or chest wall sarcomas, as well as patients with gastric, colorectal or renal cancers and sarcomas metastatic to the thorax are eligible
  • Histologic confirmation of disease in the Laboratory of Pathology, CCR, NCI, NIH.
  • Disease amenable to biopsy via percutaneous approach or other minimally invasive procedures such as thoracoscopy, bronchoscopy, laparoscopy, or GI endoscopy
  • Age >18
  • ECOG status 0-2.
  • Patients must have had or refused first-line standard chemotherapy for their inoperable malignancies.
  • Patients must have had no chemotherapy, biologic therapy, or radiation therapy for their malignancy for at least 30 days prior to treatment. Patients may have received localized radiation therapy to non-target lesions provided that the radiotherapy is completed 14 days prior to commencing therapy, and the patient has recovered from any toxicity. At least 3 half-lives must have elapsed since monoclonal antibody treatment. At least six weeks must have elapsed between mitomycin C or nitrosourea treatment.
  • Patients must have adequate organ and marrow function as defined below:

    a) Hematologic and Coagulation Parameters:

    i. Peripheral ANC greater than or equal to 1500/mm^3

ii. Platelets greater than or equal to 100,000/ mm^3 (transfusion independent)

iii. Hemoglobin greater than or equal to 8 g/dL (PRBC transfusions permitted)

iv. PT/PTT within normal limits ( 11.6 - 15.2 / 25.3 - 37.3 sec)

b) Hepatic Function

i. Bilirubin (total) < 1.5 times upper limit of normal (ULN)

ii. ALT (SGPT) less than or equal to 3.0 times ULN

iii. Albumin > 2 g/dL

c) Renal Function

i. Creatinine within normal institutional limits or creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.

ii. Normal ionized calcium, magnesium and phosphorus (can be on oral supplementation)

  • Cardiac Function: Left ventricular ejection fraction (EF) >40% by Echocardiogram, MUGA, or cardiac MR.
  • Ability of subject to understand, and be willing to sign informed consent.
  • Female and male patients (and when relevant their partners) must be willing to practice birth control (including abstinence) during and for two months after treatment, if of childbearing potential during sexual contact with a female of childbearing potential.
  • Patients must be willing to undergo 2 tumor biopsies

EXCLUSION CRITERIA:

  • Patients with ABCB4 and ABCB11 genotypes associated with mithramycin-mediated hepatotoxicity.
  • Clinically significant systemic illness (e.g. serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgment of the PI would compromise the patient s ability to tolerate protocol therapy or significantly increase the risk of complications
  • Patients with cerebral metastases
  • Patients with any of the following pulmonary function abnormalities will be excluded: FEV, < 30% predicted; DLCO, < 30% predicted (post-bronchodilator); pO2 < 60 mm Hg or pCO2 greater than or equal to 55 mm Hg on room air arterial blood gas.
  • Patients with evidence of active bleeding, intratumoral hemorrhage or history of bleeding diatheses, unless specifically occurring as an isolated incident during reversible chemotherapy induced thrombocytopenia
  • Patients on therapeutic anticoagulation. Note: prophylactic anticoagulation (i.e. intralumenal heparin) for venous or arterial access devices is allowed
  • Patients who are concurrently receiving or requiring any of the following agents, which may increase the risk for mithramycin related toxicities, such as hemorrhage:

    • Thrombolytic agents
    • Aspirin or salicylate-containing products, which may increase risk of hemorrhage
    • Dextran
    • Dipyridamole
    • Sulfinpyrazone
    • Valproic acid
    • Clopidogrel
  • Lactating or pregnant females (due to risk to fetus or newborn, and lack of testing for excretion in breast milk)
  • Patients with history of HIV, HBV or HCV due to potentially increased risk of mithramycin toxicity in this population
  • Hypersensitivity to mithramycin
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624090

Contacts
Contact: Tricia Kunst, R.N. (301) 451-1233 kunstt@mail.nih.gov
Contact: David S Schrump, M.D. (301) 496-2128 david_schrump@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505    ncisbirc@mail.nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: David S Schrump, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01624090     History of Changes
Other Study ID Numbers: 120151  12-C-0151 
Study First Received: June 16, 2012
Last Updated: September 28, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cancer Stem Cell
Thoracic Malignancies
Mythramycin Treatment
Lung Tumors
Metastatic Lung Tumors

Additional relevant MeSH terms:
Mesothelioma
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Plicamycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016