Feasibility Trial of Pembrolizumab in Unresectable Thymoma and Thymic Carcinoma

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT03295227

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arm

17.8

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There are 2 parts in this study.

The goal of Part 1 of this clinical research study is to confirm the highest tolerable dose of pembrolizumab that can be given to patients with unresectable thymoma or thymic cancer.

The goal of Part 2 of this clinical research study is to learn if pembrolizumab given at the dose that was found in Part 1 of the study can help to control thymoma or thymic cancer.

The safety of the study drug will be studied in both parts.

This is an investigational study. Pembrolizumab is FDA approved and commercially available for treatment of many types of cancers. It is considered investigational to use pembrolizumab to treat thymoma or thymic cancer.

The study doctor can describe how pembrolizumab is designed to work.

Up to 30 participants will be enrolled in this study. All will take part in MD Anderson.

Condition or Disease	Intervention/Treatment	Phase
Thymoma Thymic Cancer	Drug: Pembrolizumab	Phase 1

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 6 participants will be enrolled in Part 1 of the study, and up to 24 participants will be enrolled in Part 2.

All participants will receive the same dose of pembrolizumab.

Study Drug Administration:

Each cycle is 21 days.

You will receive pembrolizumab by vein over about 30 minutes on Day 1 of every Cycle.

Length of Study:

You may take the study drug for up to 2 years. 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.

Your participation in this study will be over after the follow-ups.

Study Visits:

On Day 1 of each Cycle:

You will have a physical exam.
Blood (about 4-6 teaspoons) will be drawn for routine tests. At Cycle 1, this blood sample will also be used for antibody testing. Antibodies are created by the immune system and may attack foreign cells or substances, such as the study drug.

Every 6 weeks, you will have an MRI and/or CT scan to check the status of the disease.

End of Dosing Visits:

After you stop receiving the study drug, and then again 30 days after that:

You will have a physical exam.
Blood (about 3 tablespoons) will be drawn for routine tests.
If it has been more than 8 weeks since your last scan, you may have an MRI and/or CT scan.

Follow-Up:

If you stopped receiving the study drug for reasons other than the disease getting worse, you will continue to have MRI and/or CT scans every 6 weeks. After 1 year, this will be reduced to every 9 weeks. These scans will continue unless the disease gets worse or you start a new anti-cancer therapy.

You will be called every 3 months for up to 3 years and asked about any cancer treatments you may be receiving. This phone call should take about 10 minutes.

Your medical record will also be reviewed every 8 weeks to check for changes in your health.

Re-Treatment:

If the disease appears to be getting worse or the tumors appear to be getting larger after you stop study treatment, you may still be able to receive the study drug if you and your doctor decide it is in your best interest. Sometimes the disease appears to get worse but the study drug is actually working.

However, there are risks of continuing to receive the study drug because the disease may actually be getting worse. You are still at risk for side effects due to the study drug. This could also delay starting other treatments. The disease may get worse to the point that you are no longer able to receive other treatments.

If you choose to receive the study drug after the disease gets worse, you will continue to have study visits as described above. The study doctor will discuss this option with you.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Feasibility Trial of Pembrolizumab in Unresectable Thymoma and Thymic Carcinoma

Actual Study Start Date :

Dec 6, 2017

Anticipated Primary Completion Date :

Jun 1, 2019

Anticipated Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab Part 1: Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of every 21 day Cycle. Part 2: Participants received Pembrolizumab at the maximum tolerated dose from Part 1.	Drug: Pembrolizumab Part 1: 200 mg by vein on Day 1 of every 21 day cycle. Part 2: Maximum tolerated dose from Part 1. Other Names: Keytruda MK-3475 SCH-900475

Arm

Intervention/Treatment

Experimental: Pembrolizumab

Part 1: Participants receive Pembrolizumab by vein over about 30 minutes on Day 1 of every 21 day Cycle. Part 2: Participants received Pembrolizumab at the maximum tolerated dose from Part 1.

Drug: Pembrolizumab

Part 1: 200 mg by vein on Day 1 of every 21 day cycle. Part 2: Maximum tolerated dose from Part 1.

Other Names:

Keytruda

MK-3475

SCH-900475

Outcome Measures

Primary Outcome Measures

Dose Limiting Toxicity (DLT) of Pembrolizumab in Unresectable Thymoma and Thymic Carcinoma [21 days]
DLT defined as having the development of grade 5 non-hematologic toxicity or grade 4-5 autoimmune diseases that are possibly, probably or definitely related to protocol treatment.

Secondary Outcome Measures

Response Rate of Pembrolizumab in Unresectable Thymoma and Thymic Carcinoma [Every 6 weeks up to 2 years]
Response rate assessed by the site investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Unresectable thymoma or thymic carcinoma
Any line of prior therapy allowed
Be willing and able to provide written informed consent/assent for the trial.
Be >/= 18 years of age on day of signing informed consent.
Have measurable disease based on RECIST 1.1.
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
Have a performance status (PS) of 0 or 1 on the ECOG PS
No history of or current diagnosis of a 'significant autoimmune disease" or paraneoplastic autoimmune disease, i.e. myasthenia gravis, Lambert-Eaton, systemic lupus, rheumatoid arthritis. For minor 'autoimmune' disorders such as psoriasis, arthritis (not including rheumatoid arthritis), Reynauld's disease; these are allowed onto trial.
No active hepatitis or diagnosis of HIV disease
No prior malignancy unless it was cured over 2 years ago; i.e. prostate cancer, or early stage (I-III) solid tumors. Patients with a prior basal skin cancer or squamous cell carcinoma of the skin or in situ cervical malignancy that have undergone curative treatment are excluded from this requirement.
Demonstrate adequate organ function as defined below all screening labs should be performed within 10 days of treatment initiation. Hematological: absolute neutrophil count >/= 1500/mcL; platelets >/= 100000mcL; hemoglobin >/= 9g/dL or >/= 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment). Renal: serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) </= 1.5 X upper limit of normal (ULN) OR >/= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. Hepatic: serum total bilirubin </- 1.5 X ULN OR direct bilirubin </= ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) </= 2.5 X ULN OR </= 5 X ULN for subjects with liver metastases; albumin >/= 2.5mg/dL.
Continue from #11: Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) </=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants </= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Note: Creatinine clearance should be calculated per institutional standard.
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Female subjects of childbearing potential must be willing to use an adequate method of contraception - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Male subjects of childbearing potential must agree to use an adequate method of contraception - Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria:

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Subjects with </= Grade 2 neuropathy are an exception to this criterion and may qualify for the study. - Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.