Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

  • STATUS
    Recruiting
  • End date
    Aug 31, 2021
  • participants needed
    818
  • sponsor
    National Cancer Institute (NCI)
Updated on 26 November 2020
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ct scan
vasectomy
mucinous adenocarcinoma
metastases
estimated creatinine clearance
gonadotropin
cancer
octreotide
remission
total bilirubin
tubal ligation
hysterectomy
lymphoma
immunosuppressive
beta-human chorionic gonadotropin
absolute neutrophil count
amylase
monoclonal antibodies
metastatic disease
pituitary
systemic therapy
immunosuppressive agents
human immunodeficiency virus
measurable disease
carcinoma
lipase
somatostatin
hydrocortisone
thyroxine
squamous cell carcinoma
lung cancer
oophorectomy
computed tomography
iv infusion
ultrasound examination
immunosuppressive therapy
bilateral oophorectomy
MRI
gilbert's syndrome
prophylaxis
adrenaline
major surgery
gilbert's disease
human chorionic gonadotropin
metastasis
neutrophil count
pancreatic adenocarcinoma
tumor cells
other malignancy
primary tumor
brain metastases
pd-l1
bone scan
leuprolide
bone metastases
nivolumab
ipilimumab
desmoid tumor
infertility
ACTH
solid tumors
parathyroid
pheochromocytoma
corticotropin
adrenal tumor
pecoma
giant cell tumors
androgen
cns disease
immunosuppression
free thyroxine
adenocarcinoma
solid tumour
squamous cell carcinoma of the head and neck
ovarian cancer
autoimmune disease
squamous cell carcinoma of head and neck
chordoma
endocrine carcinoma
gonadotrophin releasing hormone
beta-hcg
other cancer
testicular
thyroiditis
desmoid tumors
angiosarcoma
neuroendocrine carcinoma
extramammary paget's disease
transitional cell carcinoma
cholangiocarcinoma
gallbladder cancer
extrahepatic cholangiocarcinoma
intrahepatic bile duct carcinoma
germ cell tumor
neuroendocrine tumor
administration intravenous
cancer other
undifferentiated carcinoma
teratoma with malignant transformation
carcinoid
lepidic predominant adenocarcinoma
mullerian mixed tumor
peritoneal mesothelioma
thyroidectomy
carcinosarcoma
serous adenocarcinoma
seminoma
ovarian epithelial carcinoma
serous cystadenocarcinoma
cancer of the ovary
teratoma
trophoblastic tumor
trophoblastic disease
choriocarcinoma
germ cell tumor of ovary
pheochromocytoma, malignant
carcinoma lung
spindle cell carcinoma of kidney
adenosarcoma
gastrointestinal stromal tumor
metastatic malignancy
adrenal pheochromocytoma
bronchoalveolar carcinoma
adenoid cystic carcinoma
stromal tumor

Summary

This phase II trial studies nivolumab and ipilimumab in treating patients with rare tumors. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

This trial enrolls participants for the following cohorts based on condition:

  1. Epithelial tumors of nasal cavity, sinuses, nasopharynx: A) Squamous cell carcinoma with variants of nasal cavity, sinuses, and nasopharynx and trachea (excluding laryngeal, nasopharyngeal cancer [NPC], and squamous cell carcinoma of the head and neck [SCCHN])
  2. Adenocarcinoma and variants of nasal cavity, sinuses, and nasopharynx (closed to accrual 07/27/2018)
  3. Epithelial tumors of major salivary glands (closed to accrual 03/20/2018)
  4. Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location (closed to accrual)
  5. Undifferentiated carcinoma of gastrointestinal (GI) tract
  6. Adenocarcinoma with variants of small intestine (closed to accrual 05/10/2018)
  7. Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas) (closed to accrual 10/17/2018)
  8. Fibromixoma and low grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary (closed to accrual 03/20/2018)
  9. Rare pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma. Pancreatic adenocarcinoma is not eligible
  10. Intrahepatic cholangiocarcinoma (closed to accrual 03/20/2018)
  11. Extrahepatic cholangiocarcinoma and bile duct tumors (closed to accrual 03/20/2018)
  12. Sarcomatoid carcinoma of lung
  13. Bronchoalveolar carcinoma lung. This condition is now also referred to as adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma
  14. Non-epithelial tumors of the ovary: A) Germ cell tumor of ovary B) Mullerian mixed tumor and adenosarcoma (closed to accrual 03/30/2018)
  15. Trophoblastic tumor: A) Choriocarcinoma (closed to accrual)
  16. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual)
  17. Cell tumor of the testes and extragonadal germ tumors: A) Seminoma and testicular sex cord cancer B) Non seminomatous tumor C) Teratoma with malignant transformation (closed to accrual)
  18. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis
  19. Squamous cell carcinoma variants of the genitourinary (GU) system
  20. Spindle cell carcinoma of kidney, pelvis, ureter
  21. Adenocarcinoma with variants of GU system (excluding prostate cancer) (closed to accrual 07/27/2018)
  22. Odontogenic malignant tumors
  23. Pancreatic neuroendocrine tumor (PNET) (formerly named: Endocrine carcinoma of pancreas and digestive tract.) (closed to accrual)
  24. Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017)
  25. Pheochromocytoma, malignant (closed to accrual)
  26. Paraganglioma (closed to accrual 11/29/2018)
  27. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex (closed to accrual)
  28. Desmoid tumors
  29. Peripheral nerve sheath tumors and NF1-related tumors (closed to accrual 09/19/2018)
  30. Malignant giant cell tumors
  31. Chordoma (closed to accrual 11/29/2018)
  32. Adrenal cortical tumors (closed to accrual 06/27/2018)
  33. Tumor of unknown primary (Cancer of Unknown Primary; CuP) (closed to accrual 12/22/2017)
  34. Not Otherwise Categorized (NOC) Rare Tumors [To obtain permission to enroll in the NOC cohort, contact: S1609SC@swog.org] (closed to accrual 03/15/2019)
  35. Adenoid cystic carcinoma (closed to accrual 02/06/2018)
  36. Vulvar cancer (temporarily closed to accrual)
  37. MetaPLASTIC carcinoma (of the breast) (closed to accrual)
  38. Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018)
  39. Perivascular epithelioid cell tumor (PEComa)
  40. Apocrine tumors/extramammary Paget's disease (closed to accrual)
  41. Peritoneal mesothelioma (temporarily closed to accrual 05/08/2020)
  42. Basal cell carcinoma (temporarily closed to accrual 04/29/2020)
  43. Clear cell cervical cancer
  44. Esthenioneuroblastoma (closed to accrual)
  45. Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual)
  46. Clear cell ovarian cancer (closed to accrual)
  47. Gestational trophoblastic disease (GTD)
  48. Gallbladder cancer
  49. Small cell carcinoma of the ovary, hypercalcemic type
  50. PD-L1 amplified tumors
  51. Angiosarcoma
  52. High-grade neuroendocrine carcinoma (pancreatic neuroendocrine tumor [PNET] should be enrolled in Cohort 22; prostatic neuroendocrine carcinomas should be enrolled into Cohort 52). Small cell lung cancer is not eligible (temporarily closed to accrual 03/25/2020)
  53. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)

Description

PRIMARY OBJECTIVES:

I. To evaluate the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 overall response rate (ORR) in subsets of patients with advanced rare cancers treated with ipilimumab plus nivolumab combination immunotherapy.

II. To evaluate the overall response rate (ORR) in patients with gestational trophoblastic tumors treated with ipilimumab plus nivolumab combination immunotherapy.

III. To evaluate the RECIST v1.1 overall response rate (ORR) in patients PD-L1 amplified cancers treated with nivolumab immunotherapy.

SECONDARY OBJECTIVES:

I. To evaluate toxicities in each cohort. II. To estimate overall survival (OS), progression-free survival (PFS), clinical benefit rate; and to estimate immune related (i)RECIST ORR (iORR), and iRECIST PFS (iPFS) across cohorts and within each cohort.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (ALL COHORTS EXCEPT THE PD-L1 AMPLIFIED COHORT): Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 42 days for up to 17 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients who complete 17 cycles (2 years) of therapy, may continue receiving the same treatment with nivolumab and ipilimumab, or receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) per physician discretion in the absence of disease progression or unacceptable toxicity. Patients who stop treatment prior to the completion of 17 cycles of therapy may receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) in the absence of disease progression or unacceptable toxicity.

ARM II (PD-L1 AMPLIFIED COHORT): Patients receive nivolumab IV over 30 minutes on days 1, 15 and 29. Treatment repeats every 42 days for up to 17 cycles (2 years) in the absence of disease progression or unacceptable toxicity. After 17 cycles (2 years) of therapy, patients may receive nivolumab once every 14 or 28 days (2 weeks or 4 weeks) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 10 years from registration.

Details
Treatment Ipilimumab, Nivolumab, biospecimen collection
Clinical Study IdentifierNCT02834013
SponsorNational Cancer Institute (NCI)
Last Modified on26 November 2020

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Eligibility

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Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Peritoneal Mesothelioma or Rare Diseases or Lung Carcinoid Tumor or Cholangiocarcinoma or Colorectal Squamous Cell Carcinoma or Dermoid Cyst or Ovaria...?
Do you have any of these conditions: Nasal Cavity Adenocarcinoma or Placental Choriocarcinoma or islet cell cancer or Gastric Squamous Cell Carcinoma or Oral Cavity Carcinoma or Pseudomyx...?
Do you have any of these conditions: Endometrial Transitional Cell Carcinoma or mucinous carcinoma or mpnst or parathyroid carcinomas or Ovarian Clear Cell Adenocarcinoma or serous adenoc...?
Do you have any of these conditions: Ureter Squamous Cell Carcinoma or angiosarcoma or Malignant Testicular Sex Cord-Stromal Tumor or Placental Choriocarcinoma or Soft Tissue Sarcoma or S...?
Do you have any of these conditions: Nasal Cavity Adenocarcinoma or Oral Cavity Cancer or nasopharyngeal carcinoma or Gastric Neuroendocrine Carcinoma or Islet cell carcinoma or adenocarc...?
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 (COHORT #50) ONLY: All solid tumors (excluding lymphoma) are allowed for the PD-L1 amplified cohort if they have PD-L1 amplification; patients may be considered for registration to the PD-L1 amplified cohort (Cohort #50) with the confirmation of at least one of the study chairs; 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 lab; (Immunohisochemistry [IHC] and fluorescence in situ hybridization [FISH] are not allowed); the assay must be done at or after the diagnosis of advanced disease, but PRIOR TO REGISTRATION; NOTE: patients with PD-L1 overexpression by IHC or PD-L1 amplification by FISH do not quality for this cohort; 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 with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible
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
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; at pre-registration, if TSH is not within normal limits, then free T4 must be performed and must be within normal range for patient to be eligible; Note: TSH, with reflex T4 (if TSH is abnormal) is allowable if per institutional standard, provided that free T4 is within normal range; 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 cortisol levels within institutional normal ranges (ante meridiem [AM] cortisol preferred), OR adrenocorticotropic hormone (ACTH) values within the institutional normal ranges within 28 days prior to registration; if cortisol levels are not within normal limits prior to registration, then ACTH must be performed and must be within normal ranges for patient to be eligible; Note: Neither cortisol nor ACTH levels are 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 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 have amylase or lipase within =< 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration
Patients must have fully recovered from any adverse effects of major surgery (to =< grade 1) at least 14 days prior to registration

Exclusion Criteria

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 are not eligible if they have had or are planned for solid organ transplant
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
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 and no residual hepatic impairment are eligible
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 prednisone dose >= 10 mg); 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 Crohn'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]); central nervous system (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 not have symptomatic interstitial lung disease or pneumonitis
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ct scan
vasectomy
mucinous adenocarcinoma
metastases
estimated creatinine clearance
gonadotropin
cancer
octreotide
remission
total bilirubin
tubal ligation
hysterectomy
lymphoma
immunosuppressive
beta-human chorionic gonadotropin
absolute neutrophil count
amylase
monoclonal antibodies
metastatic disease
pituitary
systemic therapy
immunosuppressive agents
human immunodeficiency virus
measurable disease
carcinoma
lipase
somatostatin
hydrocortisone
thyroxine
squamous cell carcinoma
lung cancer
oophorectomy
computed tomography
iv infusion
ultrasound examination
immunosuppressive therapy
bilateral oophorectomy
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gilbert's syndrome
prophylaxis
adrenaline
major surgery
gilbert's disease
human chorionic gonadotropin
metastasis
neutrophil count
pancreatic adenocarcinoma
tumor cells
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brain metastases
pd-l1
bone scan
leuprolide
bone metastases
nivolumab
ipilimumab
desmoid tumor
infertility
ACTH
solid tumors
parathyroid
pheochromocytoma
corticotropin
adrenal tumor
pecoma
giant cell tumors
androgen
cns disease
immunosuppression
free thyroxine
adenocarcinoma
solid tumour
squamous cell carcinoma of the head and neck
ovarian cancer
autoimmune disease
squamous cell carcinoma of head and neck
chordoma
endocrine carcinoma
gonadotrophin releasing hormone
beta-hcg
other cancer
testicular
thyroiditis
desmoid tumors
angiosarcoma
neuroendocrine carcinoma
extramammary paget's disease
transitional cell carcinoma
cholangiocarcinoma
gallbladder cancer
extrahepatic cholangiocarcinoma
intrahepatic bile duct carcinoma
germ cell tumor
neuroendocrine tumor
administration intravenous
cancer other
undifferentiated carcinoma
teratoma with malignant transformation
carcinoid
lepidic predominant adenocarcinoma
mullerian mixed tumor
peritoneal mesothelioma
thyroidectomy
carcinosarcoma
serous adenocarcinoma
seminoma
ovarian epithelial carcinoma
serous cystadenocarcinoma
cancer of the ovary
teratoma
trophoblastic tumor
trophoblastic disease
choriocarcinoma
germ cell tumor of ovary
pheochromocytoma, malignant
carcinoma lung
spindle cell carcinoma of kidney
adenosarcoma
gastrointestinal stromal tumor
metastatic malignancy
adrenal pheochromocytoma
bronchoalveolar carcinoma
adenoid cystic carcinoma
stromal tumor

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