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.
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.
Inclusion Criteria:
1. Unresectable thymoma or thymic carcinoma
2. Any line of prior therapy allowed
3. Be willing and able to provide written informed consent/assent for the trial.
4. Be >/= 18 years of age on day of signing informed consent.
5. Have measurable disease based on RECIST 1.1.
6. 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.
7. Have a performance status (PS) of 0 or 1 on the ECOG PS
8. 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.
9. No active hepatitis or diagnosis of HIV disease
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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:
1. 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.
2. 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.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. Has a history of (non-infectious) pneumonitis that required steroids, or current
pneumonitis.
11. Has an active infection requiring systemic therapy.
12. 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.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. 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.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
18. 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.
