Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to find the highest tolerable dose of gemcitabine that can be given by inhalation (breathing it as a mist) to patients with solid tumors that have spread to the lungs from other parts of the body.
The safety and side effects of this drug will also be studied.
This is an investigational study. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic and lung cancer, and other solid tumors. Its administration by inhalation is investigational. The study doctor can explain how the study drug is designed to work.
Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Patients with diagnosis of solid tumor with lung metastases and patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
Willing to comply with protocol therapy and required safety monitoring (self-report, pulse oximetry, remote spirometry, labs).
Adequate organ function as defined by: peripheral absolute neutrophil count (ANC) >/= 1,000/mm3, platelet count >/= 100,000/mm3 (transfusion independent defined as not receiving platelet transfusions within a 7 day period prior to enrollment), hemoglobin >/= 8.0g/dl (may receive RBC transfusions), renal-creatinine </= 2 x ULN; hepatic- bilirubin and AST </= 5x ULN; pulmonary: FVC >/=50% predicted, Oxyhemoglobin saturation at rest >/=95% (off supplemental oxygen).
Patient age >/= 12 years and </= 50 years.
Disqualifiers
Currently being treated with bronchodilators or corticosteroids or known to have active asthma. This will not include patients who suffered from asthma as a child and outgrew it.
Pregnant or breastfeeding women will not be entered into this study due to risks of fetal and teratogenic adverse events as seen in animal studies. Pregnancy tests must be obtained in females who are post-menarchal and of child bearing potential (e.g. female that has not been amenorrheic for at least 12 consecutive months or surgically sterilized). Males or females of reproductive potential will not participate unless they have agreed to use effective contraception for the entire period in which they are receiving protocol therapy and for at least one month after treatment ends. Effective contraception is defined as intrauterine device (IUD), hormonal (birth control pill, injections, implants, patch), tubal ligation and partner's vasectomy. Abstinence is an acceptable method of birth control.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, bradycardia, related to cardiac disease, bundle branch block, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Subjects with baseline symptoms of fever and/or cough and/or shortness of breath and/or wheezing and/or fatigue grade >/= 2 (CTCAE v4.0).
Trial design
Design model
Single group
Treatments tested in this trial
Gemcitabine
Drug
Nebulized dose of aerosol GCB twice a week continuously (escalating treatment dose schema, starting at 0.75 mg/kg to 3.0 mg/kg). Participants receive a pre-determined volume of nebulized solution, according to the dose level and weight of the participant, with each aerosol GCB administration. One cycle is 4 weeks in duration.
Treatment groups
44 Participants
are divided into 1 treatment group
Group A: Aerosol Gemcitabine (GCB)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Maximum Tolerated Dose (MTD) Recommended for Phase 2 Dose of Aerosol Gemcitabine (GCB)
MTD is defined as highest dose level with six patients with at most 1 dose limiting toxicity (DLT) occurring during cycle 1. Dose levels will continue to be increased until 1 participant experiences DLT. If only 1 of 3 participants experiences DLT, 3 additional patients will be entered.
Dose escalation conducted via accelerated titration method for first 2 dose levels followed by 3+3 method for remaining dose levels. Cohorts of 1 participant per dose level for first 2 dose levels. If at any time during cycle 1 there is an instance of pulmonary grade 2 toxicity or pulmonary function tests (PFT) decline\>10% related to study drug, current dose level expanded to 3 participants \& switched to 3+3 design. If neither of these nor any other DLT occur in dose levels 1-2, switch will be to the 3 + 3 design beginning with dose level 3. Three participants will be treated at dose level 3, if still no DLT, 3 more treated at dose level 4.
Time frame
4 weeks
2
Toxicities of Aerosol Gemcitabine (GCB)
Dose limiting toxicities associated with the MTD of aerosol GCB using the NCI Common Terminology Criteria version 4 for Adverse Events (CTCAE) will be utilized for AE reporting. DLT defined as any of the following events that are at least (possibly, probably or definitely) attributable to aerosol GCB. The observation period for the purposes of dose-escalation will be the first cycle of therapy.
DLT Definition includes:
* Any episode of respiratory (bronchospasm, cough and/or dyspnea) grade 2 toxicity.
* or \> 10% decrease in FEV1 that persists \> 3 days after the drug is stopped or recurrent episode of respiratory (bronchospasm, cough and/or dyspnea) grade 2 toxicity.
* Any grade 3 or 4 non-hematological toxicity.
* Any grade 4 neutropenia or thrombocytopenia.
Time frame
Reviewed with each 4 week cycle, up to 24 weeks for six dose levels
Secondary outcomes
1
Assessment of Serum Levels of Aerosol Gemcitabine (GCB)
Assessment of serum levels of Gemcitabine (GCB) for evidence of spillover into the circulation and correlate with presence or absence of toxicity.
Time frame
Day 1 of therapy
2
Response of Serum Levels of Aerosol Gemcitabine (GCB)
Response evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time frame
Baseline, end of Cycles 2, 4, and 6, and then every 3 cycles up to 30 days after study dose stopped. Cycles are 28 days.
Other outcomes
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