Primary Outcomes:

Primary Outcome 1 - Measure: ORR defined as confirmed and unconfirmed complete and partial response, assessed by RECIST 1.1

Primary Outcome 1 - Time Frame: Up to 10 years

Condition:

• Acinar Cell Carcinoma
• Adrenal Cortex Carcinoma
• Adrenal Gland Pheochromocytoma
• Anal Canal Neuroendocrine Carcinoma
• Anal Canal Undifferentiated Carcinoma
• Appendix Mucinous Adenocarcinoma
• Bartholin Gland Transitional Cell Carcinoma
• Bladder Adenocarcinoma
• Bronchioloalveolar Carcinoma
• Cervical Adenocarcinoma
• Cholangiocarcinoma
• Chordoma
• Colorectal Squamous Cell Carcinoma
• Dermoid Cyst
• Endometrial Transitional Cell Carcinoma
• Endometrioid Adenocarcinoma
• Esophageal Neuroendocrine Carcinoma
• Esophageal Undifferentiated Carcinoma
• Extrahepatic Bile Duct Carcinoma
• Fallopian Tube Adenocarcinoma
• Fallopian Tube Transitional Cell Carcinoma
• Fibromyxoid Tumor
• Gastric Neuroendocrine Carcinoma
• Gastric Squamous Cell Carcinoma
• Giant Cell Carcinoma
• Intestinal Neuroendocrine Carcinoma
• Intrahepatic Cholangiocarcinoma
• Lung Carcinoid Tumor
• Lung Sarcomatoid Carcinoma
• Major Salivary Gland Carcinoma
• Malignant Odontogenic Neoplasm
• Malignant Peripheral Nerve Sheath Tumor
• Malignant Testicular Sex Cord-Stromal Tumor
• Metastatic Malignant Neoplasm of Unknown Primary Origin
• Mixed Mesodermal (Mullerian) Tumor
• Mucinous Adenocarcinoma
• Mucinous Cystadenocarcinoma
• Nasal Cavity Adenocarcinoma
• Nasal Cavity Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Papillary Adenocarcinoma
• Nasopharyngeal Undifferentiated Carcinoma
• Oral Cavity Carcinoma
• Oropharyngeal Undifferentiated Carcinoma
• Ovarian Adenocarcinoma
• Ovarian Germ Cell Tumor
• Ovarian Mucinous Adenocarcinoma
• Ovarian Squamous Cell Carcinoma
• Ovarian Transitional Cell Carcinoma
• Pancreatic Acinar Cell Carcinoma
• Pancreatic Neuroendocrine Carcinoma
• Paraganglioma
• Paranasal Sinus Adenocarcinoma
• Paranasal Sinus Carcinoma
• Parathyroid Gland Carcinoma
• Pituitary Gland Carcinoma
• Placental Choriocarcinoma
• Placental-Site Gestational Trophoblastic Tumor
• Primary Peritoneal High Grade Serous Adenocarcinoma
• Pseudomyxoma Peritonei
• Scrotal Squamous Cell Carcinoma
• Seminal Vesicle Adenocarcinoma
• Seminoma
• Serous Cystadenocarcinoma
• Small Intestinal Adenocarcinoma
• Small Intestinal Squamous Cell Carcinoma
• Spindle Cell Neoplasm
• Squamous Cell Carcinoma of the Penis
• Teratoma With Malignant Transformation
• Testicular Non-Seminomatous Germ Cell Tumor
• Thyroid Gland Carcinoma
• Tracheal Carcinoma
• Transitional Cell Carcinoma
• Undifferentiated Gastric Carcinoma
• Ureter Adenocarcinoma
• Ureter Squamous Cell Carcinoma
• Urethral Adenocarcinoma
• Urethral Squamous Cell Carcinoma
• Vaginal Adenocarcinoma
• Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
• Vulvar Adenocarcinoma
• Vulvar Squamous Cell Carcinoma

Eligibility

Criteria:
Inclusion Criteria:

- Patients must have histologically confirmed rare cancer and/or cancer of unknown
primary, that did not have a match to a molecularly-guided therapy on EAY131 National
Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH)" protocol or who
progressed on molecularly-matched therapy and have no further molecularly-matched
treatment recommendations per EAY131, "NCI-MATCH"

- All baseline assessments must have been completed within 28 days prior to
registration

- Patients that do not qualify for one of the histologic cohorts may be considered for
registration in the "Not Otherwise Categorized" Rare Tumors cohort with confirmation
of the study chairs via email

- Patients that are determined to have a rare cancer with unknown primary site are
eligible provided that there is histologic documentation of metastatic malignancy with
no discernible primary site identified from histopathologic review, physical exam and
associated cross-sectional imaging of the chest, abdomen, and pelvis

- Patients must have a diagnostic quality computed tomography (CT) scan or magnetic
resonance imaging (MRI), performed within 28 days prior to registration, which
demonstrates measurable disease, as defined in RECIST v. 1.1; all disease must be
assessed and documented on the S1609 Baseline Tumor Assessment Form

- No other prior malignancy is allowed except for the following:

- Adequately managed stage I or II cancer from which the patient is currently in
complete remission

- Any other cancer from which the patient has been disease free for five years

- Adequately managed stage I or II follicular thyroid or prostate cancer is also
eligible, wherein patient is not required to be in complete remission

- Patients who have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not
both, provided that it is completed >= 4 weeks prior to registration for monoclonal
therapy, >= 8 weeks prior to registration if therapy involved immunestimulatory
monoclonal antibody (mAb)s, and >= 28 days for all other immunotherapy

- Patients who had prior immune-related adverse event (grade 3 or higher immune-related
pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer
vaccine, cytokine, etc.) are not eligible

- Patients with clinically controlled thyroiditis or pituitary disorders on stable
replacement therapy are eligible

- Patients are not eligible if they have had or are planned for solid organ transplant;
patients who have received allogeneic hematopoietic stem cell transplant are eligible
if the transplant occurred at least 90 days prior to registration, patient has no
prior acute graft versus host disease (GVHD), and within 48 hours of registration,
patient demonstrates at least 90% engraftment, defined as: absolute neutrophil count
(ANC) >= 500 mcl, measured over 3 consecutive days or 1 day with an ANC >= 1,000 mcl,
or platelets >= 50,000 mcl measured, wherein the patient did not receive any platelet
transfusions within 7 days prior to laboratory assessment, patients with autoimmune
disease who are otherwise eligible under criterion 5.3 k must not have received
steroid and immunosuppressive therapy within 28 days prior to registration

- Patients with brain metastases or primary brain tumors must have completed treatment,
surgery or radiation therapy >= 28 days prior to registration and have stable disease
at time of registration; metastatic brain parenchymal disease must have been treated
and patient must be off steroids for 7 days prior to registration

- Patients must not currently be receiving any other investigational agents or any other
systemic anti-cancer therapy (including radiation); in event patient recently received
any other systemic anti-cancer therapy, patient must be off therapy at least 7 days
prior to registration and any therapy-induced toxicity must have recovered to =< grade
1

- Patients must have a Zubrod performance status of 0-2

- ANC >= 1,000/mcL

- Platelets >= 75,000/mcL

- Hemoglobin >= 8 g/dL

- Total bilirubin =< 3.0 x institutional upper limit of normal (IULN) or for
documented/suspected Gilbert's disease

- Total bilirubin =< 3.0 x IULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN

- Serum creatinine =< 2.0 IULN

- Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault
formula; estimated creatinine clearance is based on actual body weight

- Patients must have adequate thyroid function, as evidenced by thyroid-stimulating
hormone (TSH), free thyroxine (T4) serum tests demonstrating values within the normal
range, within 28 days prior to registration; Note: TSH, with reflex T4 is allowable if
per institutional standard; otherwise, both TSH and free-T4 must be obtained

- Patients must have adequate adrenal axis function, as evidenced by Adrenocorticotropic
Hormone (ACTH) values within the normal ranges, within 28 days prior to registration

- Females of childbearing potential must have negative serum pregnancy test 14 days
prior to registration and agree to use birth control throughout study and for 23 weeks
after completion of protocol therapy; patients must not be pregnant or nursing;
women/men of reproductive potential must have agreed to use an effective contraceptive
method; a woman is considered to be of "reproductive potential" if she has had menses
at any time in the preceding 12 consecutive months; in addition to routine
contraceptive methods, "effective contraception" also includes heterosexual celibacy
and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
ligation; however, if at any point a previously celibate patient chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive measures

- Men of reproductive potential must have agreed to use birth control throughout the
study and for 31 weeks after completion of protocol therapy; in addition to routine
contraceptive methods, "effective contraception" also includes heterosexual celibacy
and surgery intended to prevent pregnancy (vasectomy); however, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he is responsible
for beginning contraceptive measures

- Patients must not have known active hepatitis B virus (HBV) or hepatitis virus (HCV)
infection at time of registration; patients with HBV or HCV that have an undetectable
viral load, or in the opinion of the treating investigator is well-controlled, are
eligible

- Patients who are known to be human immunodeficiency virus (HIV)-positive at
registration are eligible at the time of registration:

1. Cluster of differentiation (CD)4+ cell count greater or equal to 250 cells/mm^3

2. If patient is on antiretroviral therapy, there must be minimal interactions or
overlapping toxicity of the antiretroviral therapy with the experimental cancer
treatment; once daily combinations that use pharmacologic boosters may not be
used

3. No history of non-malignancy acquired immunodeficiency syndrome (AIDS)-defining
conditions other than historical low CD4+ cell counts

4. Probable long-term survival with HIV if cancer were not present

- Patients must not have active autoimmune disease that has required systemic treatment
in past 2 years (i.e., with use of disease modifying agents, immunosuppressive drugs,
or corticosteroids with doses higher than prednisone 10mg or equivalent). Replacement
therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis,
inflammatory bowel disease, multiple sclerosis, vasculitis, or glomerulonephritis;
patients with well-controlled systemic lupus erythematous or rheumatoid arthritis may
be eligible after communication with the study chairs at S1609SC@swog.org; vitiligo,
alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not
requiring systemic therapy within the past 3 years is permitted; short-term steroid
premedication for contrast allergy is permitted

- Patients must not have any uncontrolled intercurrent illness including (not limited
to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA]
III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks
prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of
NCI Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4 grade >= 2),
known psychiatric illness that would limit study compliance, intra-cardiac
defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>=
grade 3)

- Note: Echocardiography (ECHO) and electrocardiogram (EKG) are clinically
indicated at baseline for any patient with a history of CHF or a risk due to
underlying cardiovascular disease or prior exposure to cardiotoxic drugs; if
patient has any evidence of CHF, MI, cardiomyopathy, or myositis cardiac
evaluation (NYHA I/II) patient, cardiology consultation is also clinically
indicated at baseline (in addition to ECHO and EKG), with creatine phosphokinase
(CPK) and troponin testing
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No