Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Durvalumab

Antineoplastic Agents, Immunological

Intermittent Arm - Participants receive Selumetinib at 75 mg by mouth twice a day for 7 days on and 7 days off, and Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Short safety run-in prior to the start of randomization. Participants on the safety run-in treated with Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Safety run-in beginning dose is Selumetinib 50 mg by mouth twice a day on Days 1 through 28 of a 28 day cycle.

During the safety run in portion of the trial, enrollment will be open to all comers, regardless of KRAS mutation status.

Continuous Arm - Participants take Selumetinib twice daily on Days 1 to 28 of a 28 day cycle. Dose determined by safety run-in.

Participants receive Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

Safety Run-In - Beginning dose is Selumetinib 50 mg by mouth twice a day on Days 1 through 28 of a 28 day cycle

Intermittent Arm - Participants receive Selumetinib at 75 mg by mouth twice a day for 7 days on and 7 days off.

Continuous Arm - Participants take Selumetinib twice daily on Days 1 to 28 of a 28 day cycle. Dose determined by safety run-in.

Selumetinib

Safety Run-In, Intermittent Arm, Continuous Arm - Durvalumab 1500 mg by vein on Day 1 of a 28 day cycle.

About every 6 months, participant called by a member of the study staff to ask how participant is doing and if participant has started any new treatments outside of the study. These calls should last about 10 minutes each time.

Phone Calls

Don L. Gibbons, MD, PHD

The goal of this clinical research study is to learn if MEDI4736 given in combination with selumetinib can help to control advanced lung cancer.

The safety of this drug combination will also be studied.

Study Groups:

If participant is found to be eligible to take part in this study, participant will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group.

* If participant is in Group 1, participant will take selumetinib 2 times each day.
* If participant is in Group 2, participant will take selumetinib 2 times each day on Days 1-7 and 15-22 of each study cycle.

All participants will also receive MEDI4736.

Study Drug Administration:

Each study cycle is 28 days.

Participant should take each dose of selumetinib about 12 hours apart after fasting (having nothing to eat or drink except water) for 1 hour before and 2 hours after taking selumetinib. Participant will follow the dosing schedule to which participant has been assigned (as described above under Study Groups).

Participant should record each selumetinib dose in the dosing diary that will be given to participant. Participant should bring the diary to participant's study visits at the end of every cycle.

Both groups will receive MEDI4736 by vein over about 60 minutes on Day 1 of every cycle.

Participant will be given standard drugs to help decrease the risk of side effects. Participant may ask the study staff for information about how the drugs are given and their risks.

Length of Study:

Participant may receive the study drugs for as long as the doctor thinks is in participant's best interest. Participant will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if participant is unable to follow study directions.

Participation on the study will be over after the Follow-Up Period.

Study Visits:

About 14 days before the first dose of the study drugs:

* Participant will have a physical exam.
* Blood (about 3 teaspoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, participant will have an EKG.

On Day 1 of every cycle:

* Participant will have a physical exam.
* Blood (about 3 teaspoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, participant will have an eye exam.
* If participant can become pregnant and the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

On Day 1 of Cycle 1 and at Week 16, participant will have an EKG. Participant will have triplicate EKGs on Day 1 of Cycle 1.

At Week 8 and about every 8 weeks after that, participant will have a CT scan or MRI to check the status of the disease.

At Week 12 and about every 12 weeks after that, participant will have an ECHO or multigated acquisition (MUGA) scan.

End-of-Study Visits:

At about 30 days and 90 days after participant's last dose of the study drugs:

* Participant will have a physical exam.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* Participant will have an EKG.
* If participant can become pregnant and the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for a pregnancy test.

Follow Up Period:

About every 6 months, participant will be called by a member of the study staff to ask how participant is doing and if participant has started any new treatments outside of the study. These calls should last about 10 minutes each time.

If the doctor thinks it is needed, participant may return to the clinic for either a CT scan or MRI to check the status of the disease.

This is an investigational study. MEDI4736 and selumetinib are not FDA approved or commercially available. They are currently being used for research purposes only. The study doctor can explain how the study drugs are designed to work.

Up to 76 participants will be enrolled in this study. All will take part at MD Anderson.

MEDI4736 With Selumetinib for KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Phase II Trial of Immunotherapy With Durvalumab (MEDI4736) With Continuous or Intermittent MEK Inhibitor Selumetinib in KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Progression-free survival (PFS) defined as the duration of time from start of treatment for patients in the safety run-in and from randomization for patients who are randomized to time of progression or death, whichever occurs first.

Response rate evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

AstraZeneca

MedImmune LLC

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Musculoskeletal Diseases

Mouth and Tooth Diseases

Rare Diseases

Melanoma

Skin Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Osteosarcoma

Neoplasm Metastasis

Urologic Neoplasms

Genital Neoplasms, Female

Bone Neoplasms

Lip Neoplasms

Genital Neoplasms, Male

Skin Diseases

Neoplastic Processes

Urogenital Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Diseases, Male

Male Urogenital Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Mouth Neoplasms

Mouth Diseases

Stomatognathic Diseases

Urologic Diseases

Bone Diseases

Oral Cancer

Pharmaceutical Solutions

Gemcitabine

Antimetabolites

Dose Escalation Cohort: Participants take Gemcitabine by mist 2 times each week for 4 weeks (28 days).

Expansion Cohort: Participants with OS lung metastases receive study drug at the maximum tolerated dose from Dose Escalation Cohort.

Participants may continue to receive the study drug for up to 12 cycles per decision of doctor.

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.

Najat C. Daw-Bitar, MD

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.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of gemcitabine based on when you join this study. Up to 6 dose levels of gemcitabine will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects are seen. This will continue until the highest tolerable dose of gemcitabine is found.

Each study cycle is 28 days. You will take gemcitabine by mist 2 times each week for 4 weeks (28 days). Treatment will be administered at MD Anderson. A machine called a nebulizer will be used to make the gemcitabine mist. The study staff will provide you with protective materials and instructions on how to take the treatment. You will breathe the drug mist through the mouthpiece of the nebulizer. The study staff will tell you which days you will receive the study drug. If the doctor thinks it is in your best interest, you may continue to receive the study drug for up to 12 cycles.

Length of Study:

You may continue taking the study drug for up to 12 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. If you have developed a tumor outside of the lungs either before or while you are on study, and the doctor thinks it is in your best interest, you may have a local control procedure (such as radiation or surgery) that may help to control the disease while continuing to receive the study drug. You would sign a separate consent form explaining these procedures and their risks. If you and your doctor decide on a systemic cancer treatment by mouth or vein, you will no longer be able to receive treatment on this study. A systemic cancer treatment is designed to spread and treat cancer cells throughout the body.

Your participation on the study will be over after your last follow-up phone call.

Study Visits:

Within 3 days before Day 1 of every cycle:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check your liver function.
* You will have PFTs.
* You will have your blood oxygen level measured by pulse oximeter.
* If you can become pregnant, urine will be collected for a pregnancy test.

On Day 8 of Cycle 1:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests and to check your liver function.

You will have a CT scan at the end of Cycles 2, 4, and 6, and then every 3 cycles after that. The study doctor will tell you when you will have these scans. If you have a chest X-ray, MRI, and PET scan as part of standard of care while you are on study, the study doctor may use the results to check the status of the disease.

To avoid having to come to the study clinic too often, you may have blood draws done by your personal doctor.

You may be called by the study staff and asked about how you are doing and about any side effects about 1 day after your first 2 doses of the study drug, at the end of Cycle 1, and 1 time every 3 months after that until you leave the study or the study ends. These calls should last about 15-20 minutes each time.

Other Information:

Each day that you take study drug:

* You will write down the date and the day of the study cycle in a dosing diary given to you by the study staff. You should bring the diary to all clinic visits.
* You will be given a pulse oximeter to measure your heart rate and blood oxygen level. °You should record your results in the dosing diary.
* You will use a small hand-held device to test your lung function before the dose and answer questions about side effects you may be having.

You will also be given an electronic device (such as a laptop or tablet) so that you can upload the information from the lung function tests and send it to the study doctor. You will only be able to access study specific material on this device. The study staff will show you how to use all of the provided machines. If the device is lost, stolen, or damaged, you will need to immediately report it to the study staff and you will be responsible for its replacement.

You should bring the nebulizer with you to all study visits.

You will be asked to return the nebulizer, pulse oximeter, lung function device, and electronic device when your participation on this study is over.

End of Dosing Visit:

Within 30 days of your last dose of the study drug:

* You will have a physical exam.
* Blood (about 4 teaspoons) will be drawn for routine tests.
* You will have PFTs.
* You will have your blood oxygen level measured by pulse oximeter.
* You will have a CT scan.

Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases

Phase I Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases

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.

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.

Assessment of serum levels of Gemcitabine (GCB) for evidence of spillover into the circulation and correlate with presence or absence of toxicity.

Response evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

James B. and Lois R. Archer Charitable Foundation

Gateway for Cancer Research

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
MEDI4736 With Selumetinib for KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)	NCT03004105	Malignant Neopl... Advanced Lung C... Recurrent Nonsm...	Selumetinib Durvalumab Phone Calls	18 Years -	M.D. Anderson Cancer Center
Study of Aerosol Gemcitabine in Patients With Solid Tumors and Pulmonary Metastases	NCT03093909	Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Malignant Neopl... Melanoma and Ot...	Gemcitabine	12 Years - 50 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for malignant neoplasm of respiratory and intrathoracic organ carcinoma