Mithramycin for Lung, Esophagus, and Other Chest Cancers

NCT01624090 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 12015112-C-0151
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Esophageal Cancer; Mesothelioma; Gastrointestinal Neoplasms; Breast Cancer

Keywords

Cancer Stem Cell; Thoracic Malignancies; Mithramycin Treatment; Lung Tumors; Metastatic Lung Tumors

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Objective Response (Complete Response + Partial Response)

  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.

  Every 8 weeks until disease progression or unacceptable toxicity, over an average of 4 months.

Secondary Outcomes (1)

• 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

Study Arms (1)

1/mithramycin

EXPERIMENTAL

Single agent intravenous (IV) mithramycin

Drug: Mithramycin

Interventions

Mithramycin DRUG

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

Also known as: Mithracin

1/mithramycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Centers for Disease Control and Prevention (CDC). Smoking-attributable mortality, years of potential life lost, and productivity losses--United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008 Nov 14;57(45):1226-8.

  PMID: 19008791 BACKGROUND

• Zhai R, Chen F, Liu G, Su L, Kulke MH, Asomaning K, Lin X, Heist RS, Nishioka NS, Sheu CC, Wain JC, Christiani DC. Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma. J Clin Oncol. 2010 May 10;28(14):2445-51. doi: 10.1200/JCO.2009.26.2790. Epub 2010 Apr 12.

  PMID: 20385987 BACKGROUND

• Wright CD, Kucharczuk JC, O'Brien SM, Grab JD, Allen MS; Society of Thoracic Surgeons General Thoracic Surgery Database. Predictors of major morbidity and mortality after esophagectomy for esophageal cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database risk adjustment model. J Thorac Cardiovasc Surg. 2009 Mar;137(3):587-95; discussion 596. doi: 10.1016/j.jtcvs.2008.11.042.

  PMID: 19258071 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Esophageal Neoplasms; Mesothelioma; Gastrointestinal Neoplasms; Breast Neoplasms

Interventions

Plicamycin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Dr. David S. Schrump
• Organization: National Cancer Institute

schrumpd@nih.gov

240-858-7000

Study Officials

• David S Schrump, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 16, 2012
• First Posted: June 20, 2012
• Study Start: September 6, 2012
• Primary Completion: August 20, 2019
• Study Completion: September 27, 2019
• Last Updated: December 30, 2019
• Results First Posted: December 30, 2019

Record last verified: 2019-12

Locations

US (1)