Primary Outcome Measures
- Objective response rate [ Time Frame: Every 8 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 ]
- 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
- Platelets greater than or equal to 100,000/ mm^3 (transfusion independent)
- Hemoglobin greater than or equal to 8 g/dL (PRBC transfusions permitted)
- PT/PTT within normal limits ( 11.6 – 15.2 / 25.3 – 37.3 sec)
- Bilirubin (total) < 1.5 times upper limit of normal (ULN)
- ALT (SGPT) less than or equal to 3.0 times ULN
- Albumin > 2 g/dL
- 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
- 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
- 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 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