Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
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|ClinicalTrials.gov Identifier: NCT02834013|
Recruitment Status : Suspended (Other - Pending revision to increase accrual target)
First Posted : July 15, 2016
Last Update Posted : November 15, 2019
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:
- 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)
- Epithelial tumors of major salivary glands (closed to accrual 03/20/2018)
- Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location (closed to accrual)
- Undifferentiated carcinoma of gastrointestinal (GI) tract
- Adenocarcinoma with variants of small intestine (closed to accrual 05/10/2018)
- Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas) (closed to accrual 10/17/2018)
- Fibromixoma and low grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary (closed to accrual 03/20/2018)
- Rare pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma. Pancreatic adenocarcinoma is not eligible
- Intrahepatic cholangiocarcinoma (closed to accrual 03/20/2018)
- Extrahepatic cholangiocarcinoma and bile duct tumors (closed to accrual 03/20/2018)
- Sarcomatoid carcinoma of lung
- Bronchoalveolar carcinoma lung. This condition is now also referred to as adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma
- Non-epithelial tumors of the ovary: A) Germ cell tumor of ovary B) Mullerian mixed tumor and adenosarcoma (closed to accrual 03/30/2018)
- Trophoblastic tumor: A) Choriocarcinoma (closed to accrual 04/15/2019)
- Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual 04/15/2019)
- 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 3/15/2019)
- Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis
- Squamous cell carcinoma variants of the genitourinary (GU) system
- Spindle cell carcinoma of kidney, pelvis, ureter
- Adenocarcinoma with variants of GU system (excluding prostate cancer) (closed to accrual 07/27/2018)
- Odontogenic malignant tumors
- Pancreatic neuroendocrine tumor (PNET) (formerly named: Endocrine carcinoma of pancreas and digestive tract.)
- Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017)
- Pheochromocytoma, malignant
- Paraganglioma (closed to accrual 11/29/2018)
- Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex
- Desmoid tumors
- Peripheral nerve sheath tumors and NF1-related tumors (closed to accrual 09/19/2018)
- Malignant giant cell tumors
- Chordoma (closed to accrual 11/29/2018)
- Adrenal cortical tumors (closed to accrual 06/27/2018)
- Tumor of unknown primary (Cancer of Unknown Primary; CuP) (closed to accrual 12/22/2017)
- 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)
- Adenoid cystic carcinoma (closed to accrual 02/06/2018)
- Vulvar cancer
- MetaPLASTIC carcinoma (of the breast)
- Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018)
- Perivascular epithelioid cell tumor (PEComa)
- Apocrine tumors/extramammary Paget's disease
- Peritoneal mesothelioma
- Basal cell carcinoma
- Clear cell cervical cancer
- Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual)
- Clear cell cervical endometrial cancer
- Clear cell ovarian cancer
- Gestational trophoblastic disease (GTD)
- Gallbladder cancer
- Small cell carcinoma of the ovary, hypercalcemic type
- PD-L1 amplified tumors
- 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
- Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)
|Condition or disease||Intervention/treatment||Phase|
|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||Procedure: Biospecimen Collection Biological: Ipilimumab Biological: Nivolumab||Phase 2|
Hide Detailed Description
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.
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.
TRANSLATIONAL MEDICINE OBJECTIVES:
I. Across strata, to evaluate the association of tumor mutational burden measured by tissue sequencing with durable response (complete response [CR] or partial response [PR] lasting 24 weeks or more).
II. Within strata, to describe the mutational load and targeted sequencing of well-known oncogenes and changes in these markers of patients at up to three time points (baseline, cycle 2, and progression), and across strata to describe associations with survival outcomes.
III. Within strata, to describe the presence of germline mutations, and across strata to evaluate association with outcome.
IV. Within strata, to describe patient risk category as defined by the biodesix protein signature and change over time at up to three time points (baseline, cycle 2, progression), and across strata to evaluate associations with outcomes.
V. Across strata, to evaluate the association of PD-L1 expression (positive versus negative) with response and survival outcomes, and within strata, to characterize baseline PD-L1 prevalence.
VI. To collect specimens for banking for use in future correlative biomarker research studies.
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. Cycles repeat every 42 days 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. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 10 years from registration.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||707 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||DART: Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors|
|Actual Study Start Date :||January 13, 2017|
|Estimated Primary Completion Date :||January 9, 2024|
Experimental: Arm I (nivolumab, ipilimumab)
Patients receive nivolumab IV over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 60 minutes on day 1. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Procedure: Biospecimen Collection
Undergo optional collection of biopsy tissue and blood
Experimental: Arm II (nivolumab)
Patients receive nivolumab IV over 30 minutes on days 1, 15 and 29. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Procedure: Biospecimen Collection
Undergo optional collection of biopsy tissue and blood
- Overall response rate (ORR) [ Time Frame: Up to 10 years ]Defined as confirmed and unconfirmed complete and partial response. Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- Incidence of adverse events [ Time Frame: Up to 10 years ]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).
- Best response [ Time Frame: Up to 10 years ]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).
- Clinical benefit rate [ Time Frame: 6 months ]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).
- Overall survival (OS) [ Time Frame: From date of registration to date of death due to any cause, assessed up to 10 years ]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).
- Progression free survival (PFS) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration or death, assessed up to 10 years ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02834013
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|Principal Investigator:||Sandip P Patel||Southwest Oncology Group|