Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Gland and Hormone Related Diseases

Nervous System Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Behaviors and Mental Disorders

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Nasopharyngeal Carcinoma

Pheochromocytoma

Paraganglioma

Carcinoma

Carcinoma, Neuroendocrine

Cholangiocarcinoma

Adenocarcinoma

Carcinoma, Transitional Cell

Thyroid Neoplasms

Thyroid Diseases

Carcinoma, Squamous Cell

Pituitary Diseases

Vulvar Neoplasms

Gastrointestinal Stromal Tumors

Neuroendocrine Tumors

Carcinoma, Ductal

Carcinoma, Basal Cell

Teratoma

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma of Lung

Hemangiosarcoma

Fibromatosis, Aggressive

Adrenocortical Carcinoma

Carcinoma, Adenoid Cystic

Seminoma

Nerve Sheath Neoplasms

Neurofibrosarcoma

Trophoblastic Neoplasms

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Neoplasms, Unknown Primary

Chordoma

Carcinoma, Acinar Cell

Pseudomyxoma Peritonei

Carcinoma, Islet Cell

Paget Disease, Extramammary

Perivascular Epithelioid Cell Neoplasms

Choriocarcinoma

Sex Cord-Gonadal Stromal Tumors

Odontogenic Tumors

Neoplasms, Mesothelial

Adenocarcinoma, Bronchiolo-Alveolar

Adenocarcinoma, Papillary

Cystadenocarcinoma, Mucinous

Carcinoma, Giant Cell

Neoplasms, Germ Cell and Embryonal

Carcinoma, Endometrioid

Aggression

Fibroma

Carcinosarcoma

Mixed Tumor, Mullerian

Adenoma, Pleomorphic

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Nerve Tissue

Neoplasms, Basal Cell

Endocrine System Diseases

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Neoplasms, Cystic, Mucinous, and Serous

Germinoma

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Ovarian Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Pregnancy Complications, Neoplastic

Neoplasms, Fibrous Tissue

Sarcoma

Neoplasms, Vascular Tissue

Nervous System Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab 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. Patients undergo ECHO during screening and on study. Patients also undergo MRI or CT throughout the trial. Additionally, patients undergo blood sample collection throughout the trial.

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. Patients undergo ECHO during screening and on study. Patients also undergo MRI or CT throughout the trial. Additionally, patients undergo blood sample collection throughout the trial.

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Sandip P Patel

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

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. Patients undergo echocardiography (ECHO) during screening and on study. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Additionally, patients undergo blood sample collection throughout the trial.

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. Patients undergo ECHO during screening and on study. Patients also undergo MRI or CT throughout the trial. Additionally, patients undergo blood sample collection throughout the trial.

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

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors

Defined as confirmed and unconfirmed complete and partial response. Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

Calculated from the sequence of RECIST 1.1 and immune-related (i)RECIST objectives. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

Defined as complete response, partial response, or stable disease, estimated using both RECIST and iRECIST. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

Estimated using both RECIST and immune-related (ir) RESIST criteria (RC). Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

Estimated using both RECIST and irRC. Assuming 16 eligible patients per stratum, this will be sufficient to estimate each binary version of this endpoint within +/- 25% (95% confidence interval).

National Cancer Institute (NCI)

Recurrence

Antirheumatic Agents

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progression or unacceptable toxicity.

Patient receive oral cyclophosphamide 50 to 150mg daily continuously in the absence of disease progressive or unacceptable toxicity.

Victor Lee, MD

There is no standard third-line systemic treatment for inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). We investigated the efficacy and safety of metronomic oral cyclophosphamide as third-line treatment or beyond.

NPC is endemic in Southern China including Hong Kong. Despite aggressive definitive chemoradiotherapy for locoregionally advanced disease, still about 30% develop relapse locoregionally or distally. Salvage or second-course radical radiotherapy with or without chemotherapy may achieve durable disease control for locoregionally advanced recurrent disease. However for those who had received 2 courses of radical radiotherapy or those with distant metastases, systemic chemotherapy would be the only drug of choice. Platinum-based doublet chemotherapy including cisplatin + 5-fluorouracil, capecitabine, gemcitabine or taxane is considered the standard first-line treatment. For second-line treatment, whether platinum-based chemotherapy was given previously is a consideration. Re-challenge with cisplatin and 5-fluorouracil can be considered in patients who enjoyed a good initial response to the same regimen with an intervening disease-free period of more than 1 year.However so far there has been no recognized standard third-line systemic treatment. Metronomic oral chemotherapy may provide an ideal choice patients treated in this setting by shifting the targets from tumor cells to tumor vasculature so as to reduce the chance of drug resistance as well as offering a relatively low toxicity profile to them who have been significantly jeopardized by the long-term complications brought prior courses of radiation therapy, surgery and chemotherapy.

In view of the above, we investigated metronomic open-label oral cyclophosphamide as third-line treatment or beyond in patients with inoperable locoregionally advanced recurrent or metastatic NPC who had failed at least 2 lines of prior systemic chemotherapy.

Cyclophosphamide for Nasopharyngeal Carcinoma

Metronomic Oral Cyclosphosphamide as Third-line Systemic Treatment or Beyond in Patients With Inoperable Locoregionally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma

There is no plan for to make individual participant data available.

Interval between the date of commencement of cyclophosphamide to the date of radiologically confirmed progressive disease or death, whichever comes earlier.

The percentage of patients who demonstrate complete response or partial response after study medication as assessed by RECIST 1.1

The percentage of patients who demonstrate complete response, partial response or stable disease after study medication as assessed by RECIST 1.1

All treatment-related adverse events as assessed by CTCAE version 4.0 will be recorded

Time interval between the date of commencement of cyclophosphamide to the date of death

The University of Hong Kong

Clinical Assistant Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nivolumab and Ipilimumab in Treating Patients With Rare Tumors	NCT02834013	Acinar Cell Car... Adenoid Cystic ... Adrenal Cortica... Adrenal Gland P... Anal Canal Neur... Anal Canal Undi... Angiosarcoma Apocrine Neopla... Appendix Mucino... Bartholin Gland... Basal Cell Carc... Bladder Adenoca... Breast Metaplas... Cervical Adenoc... Cholangiocarcin... Chordoma Colorectal Squa... Desmoid Fibroma... Endometrial Tra... Endometrioid Ad... Esophageal Neur... Esophageal Undi... Extrahepatic Bi... Extramammary Pa... Fallopian Tube ... Fallopian Tube ... Fibromyxoid Tum... Gallbladder Car... Gastric Neuroen... Gastric Squamou... Gastric Undiffe... Gastrointestina... Gestational Tro... Giant Cell Carc... Human Papilloma... Intestinal Neur... Intrahepatic Ch... Lung Neuroendoc... Lung Sarcomatoi... Major Salivary ... Malignant Odont... Malignant Perip... Malignant Solid... Malignant Testi... Metastatic Mali... Metastatic Pitu... Minimally Invas... Mixed Mesoderma... Mucinous Adenoc... Mucinous Cystad... Nasal Cavity Ad... Nasal Cavity Ca... Nasopharyngeal ... Nasopharyngeal ... Nasopharyngeal ... Oral Cavity Car... Oropharyngeal U... Ovarian Adenoca... Ovarian Germ Ce... Ovarian Mucinou... Ovarian Squamou... Ovarian Transit... Pancreatic Acin... Pancreatic Neur... Paraganglioma Paranasal Sinus... Paranasal Sinus... Parathyroid Gla... PEComa Penile Squamous... Peritoneal Meso... Placental Chori... Primary Periton... Pseudomyxoma Pe... Rare Disorder Scrotal Squamou... Seminal Vesicle... Seminoma Serous Cystaden... Small Intestina... Small Intestina... Spindle Cell Ne... Teratoma With S... Testicular Non-... Thyroid Gland C... Tracheal Carcin... Transitional Ce... Ureter Adenocar... Ureter Squamous... Urethral Adenoc... Urethral Squamo... Vaginal Adenoca... Vaginal Squamou... Vulvar Carcinom...	Biospecimen Col... Computed Tomogr... Echocardiograph... Ipilimumab Magnetic Resona... Nivolumab	18 Years -	National Cancer Institute (NCI)
Cyclophosphamide for Nasopharyngeal Carcinoma	NCT02794077	Recurrent Nasop... Stage IV Nasoph...	Cyclophosphamid...	15 Years - 80 Years	The University of Hong Kong

Spots Global Cancer Trial Database for nasopharyngeal undifferentiated carcinoma