Primary Outcomes:

Primary Outcome 1 - Measure: Overall response rate (ORR)

Primary Outcome 1 - Time Frame: Up to 10 years

Condition:

• Acinar Cell Carcinoma
• Adenoid Cystic Carcinoma
• Adrenal Cortex Carcinoma
• Adrenal Gland Pheochromocytoma
• Anal Canal Neuroendocrine Carcinoma
• Anal Canal Undifferentiated Carcinoma
• Angiosarcoma
• Apocrine Neoplasm
• Appendix Mucinous Adenocarcinoma
• Bartholin Gland Transitional Cell Carcinoma
• Basal Cell Carcinoma
• Bladder Adenocarcinoma
• Cervical Adenocarcinoma
• Cervical Clear Cell Adenocarcinoma
• Cholangiocarcinoma
• Chordoma
• Colorectal Squamous Cell Carcinoma
• Desmoid-Type Fibromatosis
• Endometrial Transitional Cell Carcinoma
• Endometrioid Adenocarcinoma
• Esophageal Neuroendocrine Carcinoma
• Esophageal Undifferentiated Carcinoma
• Extrahepatic Bile Duct Carcinoma
• Extramammary Paget Disease
• Fallopian Tube Adenocarcinoma
• Fallopian Tube Transitional Cell Carcinoma
• Fibromyxoid Tumor
• Gallbladder Carcinoma
• Gastric Neuroendocrine Carcinoma
• Gastric Squamous Cell Carcinoma
• Gastric Undifferentiated Carcinoma
• Gastrointestinal Stromal Tumor
• Gestational Trophoblastic Tumor
• 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
• Metaplastic Breast Carcinoma
• Metastatic Malignant Neoplasm of Unknown Primary
• Minimally Invasive Lung Adenocarcinoma
• 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 Clear Cell 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
• PEComa
• Peritoneal Mesothelioma
• Pituitary Gland Carcinoma
• Placental Choriocarcinoma
• Primary Peritoneal High Grade Serous Adenocarcinoma
• Pseudomyxoma Peritonei
• Rare Disorder
• Scrotal Squamous Cell Carcinoma
• Seminal Vesicle Adenocarcinoma
• Seminoma
• Serous Cystadenocarcinoma
• Small Intestinal Adenocarcinoma
• Small Intestinal Squamous Cell Carcinoma
• Solid Neoplasm
• Spindle Cell Neoplasm
• Squamous Cell Carcinoma of the Penis
• Teratoma With Somatic-Type Malignancy
• Testicular Non-Seminomatous Germ Cell Tumor
• Thyroid Gland Carcinoma
• Tracheal Carcinoma
• Transitional Cell Carcinoma
• Ureter Adenocarcinoma
• Ureter Squamous Cell Carcinoma
• Urethral Adenocarcinoma
• Urethral Squamous Cell Carcinoma
• Vaginal Adenocarcinoma
• Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
• Vulvar Carcinoma

Eligibility

Criteria:
Inclusion Criteria:

- Patients are eligible under ONE of the following criteria:

- For all cohorts except the gestational trophoblastic disease (GTD) (Cohort #47),
patients must have histologically and/or biochemically confirmed rare cancer and
must be able to submit specimens. To be eligible for the GTD cohort: patients
must have disease confirmed by quantitative serum beta-human chorionic
gonadotropin (hCG) within 28 days prior to registration and must be able to
submit blood specimens (tissue submission is not required for patients who will
be registered to the GTD cohort [Cohort #47]); NOTE: Subsequent to site's
Institutional Review Board (IRB) approval of revision 3, patients are NOT
required to participate in EAY131 National Cancer Institute (NCI)-Molecular
Analysis for Therapy Choice (MATCH)" to register to S1609 OR

- FOR PATIENTS WITH PD-L1 AMPLIFICATION ONLY: All solid tumors (excluding lymphoma)
are allowed for the PD-L1 amplified cohort if they have PD-L1 amplification;
PD-L1 amplification is defined as having deoxyribonucleic acid (DNA) copy number
of equal to or greater than six by any of the following Clinical Laboratory
Improvement Act (CLIA)-approved next generation sequencing (NGS) tests:
Foundation Medicine, Caris, MSK Impact, MD Anderson, Tempus, or Neogenomics;
(fluorescence in situ hybridization [FISH] is not allowed); the assay must be
done at or after the diagnosis of advanced disease, but PRIOR TO REGISTRATION OR

- FOR PATIENTS ENROLLED IN EAY131 "NCI-MATCH" PRIOR TO EAY131 ADDENDUM 10 ONLY:
Patients must have histologically confirmed rare cancer that did not have a match
to a molecularly-guided therapy on EAY131 "NCI-MATCH" protocol or who are off
protocol treatment on EAY131, "NCI-MATCH" and have no further molecularly-matched
treatment recommendations per EAY131, "NCI-MATCH" or who are otherwise unable to
receive EAY131, "NCI-MATCH" therapy

- Patients who do not qualify for one of the histologic cohorts and are not on the
ineligible histology list may be considered for registration in the "Not Otherwise
Categorized" Rare Tumors cohort with confirmation of at least one of the study chairs
via email

- NOTE: The "Not Otherwise Categorized" Rare Tumors cohort was permanently closed
to accrual on 3/15/2019

- Patients who are determined to have a rare cancer with unknown primary site are
eligible under cohort #32 (tumor of unknown primary [cancer of unknown primary; CuP]),
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

- NOTE: The "Tumor of unknown primary (Cancer of Unknown Primary; CuP" cohort was
permanently closed to accrual on 12/22/2017

- Patients must also meet one of the following:

- Patients must have progressed following at least one line of standard systemic
therapy and there must not be other approved/standard therapy available that has
been shown to prolong overall survival (i.e. in a randomized trial against
another standard treatment or by comparison to historical controls); patients who
cannot receive other standard therapy that has been shown to prolonged survival
due to medical issues will be eligible, if other eligibility criteria are met; OR

- Patients for whose disease no standard treatment exists that has been shown to
prolong overall survival

- For all cohorts except the GTD cohort (Cohort #47): 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; scans must include imaging of the chest, abdomen and pelvis,
with the exception of patients with head/neck cancer, who must have imaging of the
chest, abdomen, pelvis and neck; if there is clinical suspicion for bone metastases at
the time of enrollment (in the judgement of the treating investigator) bone scan
should be performed; bone scans done within 42 days prior to registration may be used
to establish baseline condition at registration

- 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 one year

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

- Note: Second primary tumors are not allowed concurrent with any of the eligible
rare cancers

- For all cohorts except the PD-L1 amplified tumors cohort (Cohort # 50): Patients may
have received either prior anti-CTLA4 or other prior anti-PD-1/anti-PD-L1 therapy, but
not both, provided that it is completed >= 4 weeks prior to registration. To be
eligible for the PD-L1 amplified tumors cohort (Cohort #50): Patients must not have
received anti-PD-1/anti-PD-L1 therapy; prior anti-CTLA-4 is allowed provided that it
is completed >= 4 weeks prior to registration

- Patients who had prior grade 3 or higher immune-related adverse event (e.g.
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 with autoimmune disease who are otherwise eligible 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; these patients must also have a CT or MRI of the brain to
evaluate for CNS disease within 42 days prior to registration to S1609; 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, excluding RANKL inhibitors and
bisphosphonates); 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, except alopecia and =<
grade 2 neuropathy which are allowed; any planned radiation therapy must be completed
before registration to S1609

- Patients must not have prior history of allergy or known hypersensitivity to nivolumab
or ipilimumab

- Hormonal or endocrine blockade is permitted as long as patient has demonstrated
progression on prior therapy (e.g. gonadotrophin releasing hormone [GnRH],
somatostatin); long-acting somatostatin analogs (including octreotide) and androgen
deprivation treatment (including long-acting leuprolide) are permitted while on
protocol therapy

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

- Absolute neutrophil count (ANC) >= 1,000/mcL (within 28 days prior to registration)

- Platelets >= 75,000/mcL (within 28 days prior to registration)

- Hemoglobin >= 8 g/dL (within 28 days prior to registration)

- Total bilirubin =< 2.0 x institutional upper limit of normal (IULN) or for
documented/suspected Gilbert's disease, total bilirubin =< 3.0 x IULN (within 28 days
prior to registration)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 3 x IULN
(within 28 days prior to registration)

- Serum creatinine =< 2.0 x IULN (within 28 days prior to registration)

- Creatinine clearance (CrCl) >= 50 mL/min., as estimated by the Cockcroft and Gault
formula; estimated creatinine clearance is based on actual body weight (within 28 days
prior to registration)

- Patients must have adequate thyroid function, as evidenced by either
thyroid-stimulating hormone (TSH) or, 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; patients who have undergone
thyroidectomy or who are on thyroid suppression for their cancer are not required to
have normal TSH and free T4

- Patients must have adequate adrenal axis function, as evidenced by adrenocorticotropic
hormone (ACTH) values within the institutional normal ranges OR cortisol levels within
institutional normal ranges (ante meridiem [AM] cortisol preferred), within 28 days
prior to registration; Note: ACTH and cortisol levels are not required for patients
with primary adrenal tumors (e.g. adrenocortical carcinoma)

- For women of childbearing potential, the local investigator must rule out pregnancy;
Except for Cohorts 13 and 47, where tumor types may express beta-hCG, women of
childbearing potential must have a serum or urine pregnancy test within 7 days prior
to registration; for Cohorts 13 and 47, where tumor types may produce hCG (e.g. germ
cell tumors or trophoblastic disease), other pregnancy exclusion methods should be
used to rule out pregnancy, such as ultrasound examination, documented history of
effective contraception, or documented infertility; all females of childbearing
potential must have been demonstrated not to be pregnant within 7 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 due to risk
of fetal or nursing infant harm; women of childbearing potential must have agreed to
use an effective contraceptive method; a woman is considered to be of "childbearing
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, 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:

- CD4+ cell count greater or equal to 250 cells/mm^3

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

- 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 10 mg 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 (including ulcerative colitis and Chron's disease), as well
as symptomatic disease (e.g. rheumatoid arthritis, systemic progressive sclerosis
[scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's
Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g.,
Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis or
glomerulonephritis); vitiligo, alopecia, hypothyroidism on stable doses of thyroid
replacement therapy, psoriasis not requiring systemic therapy within the past 2 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: Patients with history of CHF or patients who are deemed at risk because of
underlying cardiovascular disease or exposure to cardiotoxic drugs should have an
electrocardiogram (EKG) and echocardiogram (ECHO), as clinically indicated, at
baseline and at the start of each cycle; patients who have evidence at baseline
(or subsequently) of CHF, myocardial infarction (MI), cardiomyopathy, or myositis
cardiac evaluation (NYHA I/II) should have additional consult by a cardiologist,
including review of EKG, creatine phosphokinase (CPK), troponin, echocardiogram,
as clinically indicated

- Patients must have amylase or lipase within =< 1.5 x IULN without symptoms of
pancreatitis at registration, within 28 days prior to registration

- Patients must not have symptomatic interstitial lung disease or pneumonitis

- Patients must have fully recovered from any adverse effects of major surgery (to =<
grade 1) at least 14 days prior to registration
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No