Mithramycin for Lung, Esophagus, and Other Chest Cancers
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|ClinicalTrials.gov Identifier: NCT01624090|
Recruitment Status : Terminated (Study closed due to low accrual.)
First Posted : June 20, 2012
Results First Posted : December 30, 2019
Last Update Posted : December 30, 2019
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- 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.
- To see if mithramycin is safe and effective against different chest cancers.
- Individuals at least 18 years of age who have lung, esophagus, pleura, or mediastinum cancers.
- 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 or disease||Intervention/treatment||Phase|
|Lung Cancer Esophageal Cancer Mesothelioma Gastrointestinal Neoplasms Breast Cancer||Drug: Mithramycin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum|
|Actual Study Start Date :||September 6, 2012|
|Actual Primary Completion Date :||August 20, 2019|
|Actual Study Completion Date :||September 27, 2019|
Single agent intravenous (IV) mithramycin
30 mcg/kg intravenous (IV) over 6 hours once daily for 7 days, to be repeated every 21 days (one cycle) until disease progression or unacceptable toxicity
Other Name: Mithracin
- 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.
- Number of Participants With Serious and Non-Serious Adverse Events [ Time Frame: 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 ]Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH).
- Disease amenable to biopsy via percutaneous approach or other minimally invasive procedures such as thoracoscopy, bronchoscopy, laparoscopy, or gastrointestinal (GI) endoscopy
- Age >18
- Eastern Cooperative Oncology Group (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 absolute neutrophil count (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 (peripheral red blood count (PRBC) transfusions permitted)
iv. Prothrombin Time (PT)/Partial Thromboplastin Time (PTT) within normal limits (patient may be eligible for trial if abnormality is deemed clinically insignificant and cleared for protocol therapy by Hematology Consult Service)
b) Hepatic Function
i. Bilirubin (total) < 1.5 times upper limit of normal (ULN)
ii. Alanine aminotransferase (ALT) (Serum glutamic pyruvic transaminase (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, multi-gated acquisition scan (MUGA), or cardiac magnetic resonance (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
- Patients with adenosine 5-triphosphate binding cassette subfamily B member 4 (ABCB4), adenosine 5-triphosphate binding cassette subfamily B member 11 (ABCB11), retinal-binding protein (RALBP) or cytochrome P851 (CYP851) 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 Principal Investigator (PI) would compromise the patients 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: forced expiratory volume (FEV), < 30% predicted; diffusing capacity for carbon monoxide (DLCO), < 30% predicted (post-bronchodilator); Oxygen saturation greater than 92% on room air. Arterial Blood Gas will be drawn if clinically indicated.
- 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. intraluminal 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
- Valproic acid
- Lactating or pregnant females (due to risk to fetus or newborn, and lack of testing for excretion in breast milk)
- Patients with history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01624090
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||David S Schrump, M.D.||National Cancer Institute (NCI)|
Documents provided by David Schrump, M.D., National Cancer Institute (NCI):
|Responsible Party:||David Schrump, M.D., Principal Investigator, National Cancer Institute (NCI)|
|Other Study ID Numbers:||
|First Posted:||June 20, 2012 Key Record Dates|
|Results First Posted:||December 30, 2019|
|Last Update Posted:||December 30, 2019|
|Last Verified:||December 2019|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Cancer Stem Cell
Metastatic Lung Tumors
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Protein Synthesis Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors