Neoplasms

All Conditions

Nervous System Diseases

Gland and Hormone Related Diseases

Adenoma

Pituitary Diseases

Pituitary Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

USE OF ENDOSPHENOIDAL COIL (ESC) TO OBTAIN MRI IMAGING OF THE PITUITARY GLAND

Michaela X Cortes

Prashant Chittiboina, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

Pituitary tumors can cause problems by secreting hormones in the body. They can also problems by growing large and pushing on organs near the pituitary gland. The best treatment for such tumors is to remove them by surgery. But that may be sometimes difficult. Some tumors maybe too small to see. Some other tumors maybe so large that portions maybe left behind during surgery. The endosphenoidal coil (ESC) is a new magnetic resonance imaging (MRI) device. It fits in a small space made during surgery near the pituitary. Researchers want to see if it helps transmit MRI signals during surgery to make better images of the pituitary gland and tumors.

Objective:

To test the safety of using a new coil device to improve MRI imaging of pituitary tumors during surgery.

Eligibility:

Adults 18-85 years old who are having pituitary tumor surgery at NIH

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Review of prior brain scans
* Blood and pregnancy tests

All participants will have MRI of pituitary gland. They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will lie still and get earplugs for loud sounds. A dye will be inserted into an arm vein by needle.

Participants will stay in the hospital for about 1 week. They will repeat screening tests.

Participants will have standard pituitary surgery. They will get medicine to go to sleep. The surgeon will create a path to the pituitary gland from under the lip.

During surgery, the ESC will be placed through the path to near the pituitary. Then an MRI will be done during surgery.

Then the ESC will be removed and standard surgery will continue.

Participants will get standard post-operative care under another protocol.

Tumors of the pituitary gland comprise up to 20% of all brain tumors. The central location and the small size of the pituitary gland make the management of tumors particularly challenging. Transsphenoidal surgery (TSS) to resect pituitary tumors is highly successful at achieving complete cure for functional pituitary adenomas. It is most successful when such adenomas can be localized by preoperative MRI of the pituitary. However, in some instances, small functional tumors cannot be visualized. In the case of Cushing s disease (CD), such non-visualization may be as high as 50%. The success of transsphenoidal surgery is substantially reduced in patients with negative MRI, as some of the adenomas that cause CD are so small that they are difficult to find during surgical exploration of the pituitary. Surgical success is also diminished when tumors invade the walls of the cavernous sinus. MRI of the pituitary lacks imaging resolution to detect such invasion and so the surgeon cannot perform a complete resection with surgery based on the preoperative MRI.

Signal to noise ratio (SNR) is the primary constraint on achieving high quality high resolution MRI images. SNR can be improved by longer scan times or by increasing the field strength of the MRI magnet. SNR is proportional to the square of imaging time, however, long imaging times are not clinically feasible. SNR is linearly proportional to field strength, however, replacing MRI magnets is cost prohibitive.

Another strong determinant of SNR is the proximity of the MRI receiver coil to the tissue being imaged. Placement of a coil in close proximity to the structure of interest dramatically increases SNR, often as much as 10-fold. Clinically this is routinely put into practice for superficial body parts, such as the temporomandibular joints, in which small coils are placed directly over the joints to achieve rapid high-resolution imaging. For deep structures, the use of superficial coils is of no benefit. This has led to the development of endocavitary coils, such as the endorectal coil used to image the prostate gland. Such coils are now in routine clinical use here at the NIH and elsewhere.

During routine TSS, the surgical approach to the pituitary provides a route for placement of imaging tools, such as handheld ultrasound and Doppler probes in close proximity to the gland. Extending this model to MRI imaging, we realized that an endocavitary surface coil within the sphenoid sinus will allow for a marked improvement in SNR for imaging the sella. To this end, we have developed an endosphenoidal coil (ESC), demonstrated its MRI safety, and performed preliminary studies in cadaver heads to determine that the ESC can be placed through the transsphenoidal approach. Placement of ESC needs no modification in the surgical TSS approach to the pituitary gland. The goal of this protocol is to examine the safety and feasibility of ESC placement and imaging during TSS.

Objective

To evaluate the feasibility and safety of using ESC during TSS.

Study Population

The study population will be up to 70 adult subjects with pituitary tumors that require TSS. Enrollment will be completed once 50 subjects have received the study procedure. The requested accrual ceiling of 70 subjects accounts for screening failures and drop-outs who do not receive the study procedure.

Design

This is a pilot study of 50 subjects requiring TSS for pituitary lesions. The subjects will undergo standard TSS resection of a pituitary adenoma in the intra-operative MR suite. Following standard surgical approach, the ESC will be placed into the sphenoid sinus, while the bone of the sellar floor is still intact. Routine clinical pituitary imaging with and without intravenous contrast will be performed for comparison with standard pituitary imaging. Additional higher resolution sequences will be performed as time allows. Following imaging, standard surgical resection will be performed. Surgeon will not view scans arising from the research procedure and therefore intraoperative clinical decisions making will not be influenced by the results of the research imaging.

Outcome Measures:

Primary Outcome Measure

Preliminary analysis of the data generated so far revealed that the ESC is well-designed to fit within the surgical workflow. However, the utility of ESC imaging was limited within the parameters of the standard sequences. Depending on the specific clinical indication for TSS, we found that the ESC could have differing roles as a surgical adjunct. For the current amended trial, feasibility of ESC will be evaluated as follows:

1. For microadenomas (pituitary adenomas smaller than 10 mm in diameter), the ability of ESC to confirm the location and size of adenomas.
2. For macroadenomas (pituitary adenomas larger than 10 mm in diameter), the ability of ESC to detect invasion of the cavernous sinus and/or parasellar structures (structures surrounding the pituitary gland).
3. For MRI negative cases, the ability to detect adenomas.

Safety Outcome Measure

We will evaluate the safety of the ESC as a surgical adjunct tool. We will evaluate whether the use of ESC causes local trauma, bleeding, burns or other unanticipated safety issues during TSS.

Exploratory Outcome Measures

Clinical utility of these images will be evaluated by comparing SNR and contrast to noise ratio (CNR) measurements obtained with the ESC to preoperative standard of care images.

1. Pituitary SNR with ESC MRI versus pre-operative standard of care images.
2. Pituitary to tumor Contrast to Noise Ratio (CNR) with ESC MRI versus pre-operative standard of care images.

Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery

.We do plan to share IPD. We will share all IPD that results in a publication on a public repository, as required by most journals. The data will be de-identified and anonymized.

The primary outcome of this study is the feasibility of using ESC as a clinical tool during transsphenoidal surgery. Feasibility will be assessed by the time added to a standard TSS procedure (measured from the time the TSS exposure is completed to the time to return to the operating position for completion of surgery).

National Institute of Neurological Disorders and Stroke (NINDS)

Digestive System Diseases

Rare Diseases

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Vaccines

Immunomodulating Agents

Monatide (IMS 3015)

Entinostat

Adjuvants, Vaccine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Adjuvants, Immunologic

Immunologic Factors

Histone Deacetylase Inhibitors

Enzyme Inhibitors

H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (Phase I component to determine lysate dose)

H1299 cell lysate vaccine with Montanide(R) ISA-51 VG, entinostat, and nivolumab (lysate at dose determined in Phase I)

Nivolumab 480 mg flat dose via intravenous infusion on Day 3 of every cycle starting at Cycle 2, for intended duration of 1 year.

Entinostat (5 mg) self-administered on Days -14 and -7 prior to the first vaccination cycle, then entinostat (3 mg) self-administered on Days 1, 8, 15, and 22 of each vaccine cycle (Cycles 1-6). Entinostat continuation for subjects with immunologic response and NED during additional 2 vaccine injections.

H1299 cell lysate with Montanide(R) ISA-51 VG adjuvant vaccine via subcutaneous injections once every cycle (1 cycle=28 days) for 6 cycles (i.e., 6 vaccinations). Dose Level 1 (DL1) starting dose is 20 mg lysate protein in 2-2.5 mL Montanide(R) ISA-51 VG adjuvant; lysate concentration will be 8-10 mg/mL. Additional 2 vaccine injections for subjects with immunologic response and NED.

Montanide(R) ISA-51 VG Adjuvant

H1299 Cell Lysates

Deneise Francis, R.N.

David S Schrump, M.D.

National Cancer Institute Referral Office

This is a Phase I/II study to determine the safety and immune response of the H1299 cell lysate vaccine mixed with Montanide(R) ISA-51 VG adjuvant, to be administered on the study in combination with Entinostat and Nivolumab in eligible participants with locally advanced esophageal cancers (EsC) following either neoadjuvant chemoradiation therapy (nCRT) or nCRT and surgery. Phase I of the protocol aims to determine the safe dose of the H1299 lung cancer cell lysate vaccine mixed with Montanide(R) ISA-51 VG adjuvant when it is administered in combination with Entinostat and Nivolumab. Phase II of the protocol will focus on assessing the level of immune response in participants receiving the study intervention when the H1299 cell lysate vaccine with Montanide(R) ISA-51 VG adjuvant is administered at the dose level determined in Phase I.

Background:

* Esophageal cancers (EsC) are highly lethal malignancies with strong predilections for local and systemic recurrences despite aggressive multimodality interventions.
* Currently the standard of care for locally advanced (stage II/III) EsC is neoadjuvant chemoradiation therapy (nCRT) and surgery.
* Nearly 50% of patients with esophageal squamous cell cancers (ESCC) and 25% of patients with esophageal adenocarcinomas (EAC) have pathologic complete responses (pCR) following nCRT.
* Current staging modalities cannot reliably detect all residual EsC following nCRT, and the benefit of surgery in patients with pCR is unclear.
* Recently nivolumab was approved as adjuvant therapy for patients who have undergone complete (R0) resections of locally advanced esophageal or gastro-esophageal junction (GEJ) carcinomas with pathologic incomplete responses (pIR) following nCRT.
* Preclinical studies and early phase clinical studies suggest that immune checkpoint inhibitors can improve the efficacy of vaccines targeting tumor associated antigens.
* Cancer-testis (CT) antigens (CTA), particularly those encoded by genes on the X chromosome (CT-X antigens) have emerged as attractive targets for cancer immunotherapy given their highly restricted expression in cancers but not normal tissues and oncogenic activities.
* Recent studies suggest that CT antigens are preferentially expressed in pluripotent stem/tumor initiating cells that mediate treatment resistance and metastasis of human cancers.
* Treatment interventions that inhibit activity of immunosuppressive Treg cells significantly increase efficacy of cancer vaccines and immune checkpoint inhibitors; the triple combination therapy cures nearly all mice with established, highly aggressive cancers.
* The class I histone deacetylase (HDAC) inhibitor, entinostat which inhibits Treg activity appears to favorably modulate immune cell subsets in patients with advanced cancers receiving nivolumab.
* Conceivably, vaccination of EsC patients with tumor cell lysates containing high levels of CT antigens in combination with entinostat will facilitate eradication of dormant EsC cells following immune checkpoint blockade.

Primary Objectives:

* Phase I: To determine the safe dose of adjuvant H1299 lung cancer cell lysate vaccines with Montanide(R) ISA-51 VG administered in conjunction with entinostat and nivolumab in participants with locally advanced esophageal cancers (EsC) with pathologic incomplete responses (pIR) following neoadjuvant chemoradiation therapy (nCRT).
* Phase II: To assess the frequency of immunologic responses to purified CT antigens in EsC participants following vaccinations with H1299 cancer cell lysates and Montanide(R) ISA- 51 VG in combination with entinostat and nivolumab.

Eligibility:

* Participants with clinical Stage II or Stage III EsC with pIR following nCRT within the past 16 weeks
* Participants must be 18 years or older with an ECOG performance status of 0 1
* Adequate bone marrow, kidney, liver, lung, and cardiac function
* No prior anti-PD-1/PD-L1 therapy for their EsC
* Participants receiving steroids at supraphysiologic doses will be excluded.
* Participants with HIV or any active infections will be excluded.

Design:

* After recovery from nCRT or nCRT and surgery, eligible participants will commence oral entinostat (5 mg q week).
* Following a two-week entinostat run-in, participants will commence monthly deep subcutaneous vaccinations with H1299 cell lysates and Montanide (r) ISA-51 VG until six vaccinations have been given (each cycle=28 days).
* Following the two-week entinostat (5 mg q week) run-in, entinostat will be administered at a dose of 3 mg q week during nivolumab therapy.
* Four weeks after the first vaccination, participants will commence nivolumab (480 mg IV infusion) monthly for 1 year.
* Each cycle of vaccine therapy is 4 weeks (28 days).
* Participants will be scanned every 12 weeks while on treatment or continued treatment, and during follow up every 3 months for 3 years, every 6 months for another 2 years or through disease progression.
* Leukapheresis will be performed at baseline and at treatment evaluation one month following completion of the six vaccinations.
* Systemic toxicities and immunologic responses to therapy will be recorded.
* Pre- and post-vaccination serologic and cell mediated responses to a panel of CT antigens will be assessed before and one month following completion of the six vaccinations.
* Individuals deemed to have responded to the vaccine regimen and exhibit no evidence of disease recurrence or secondary malignancy will be eligible for two additional vaccinations administered q3 months with weekly entinostat and monthly nivolumab.
* Numbers and percentages of immune subsets, soluble factors, and cytokines in peripheral blood will be assessed before and after the six vaccinations.
* Immunologic responses to autologous tumor cells (if available) as well as lysates from H1299 cells and EsC stem cells vs normal esophageal-induced pluripotent stem cells (Eso-iPSC) will be evaluated in an exploratory manner.
* Accrual ceiling will be set at 50 participants.

Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer

.All IPD recorded will be shared upon request.

Assessment of safety and tolerability as determined by the frequency and severity of adverse events

Assessment of immune response to CT antigens (new serologic reactivity or increase in existing antibody response to CT antigens, evidenced by IgM/IgG class switch or antibody titer)

Analyses which investigate immunologic response (i.e., immune response to CT antigens); response to vaccine will be the appearance of new serologic reactivity or an increase in existing antibody response to CT antigens, evidenced by IgM/IgG class switch or antibody titer.

Progression free survival (PFS) determined by RECIST using the Kaplan-Meier method

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery	NCT03678389	Pituitary Neopl...	ESC	18 Years - 85 Years	National Institutes of Health Clinical Center (CC)
Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery	NCT03678389	Pituitary Neopl...	ESC	18 Years - 85 Years	National Institutes of Health Clinical Center (CC)
Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer	NCT05898828	Neoplasms Esophageal Neop... Esophagus Neopl... Esophagus Cance... Neoplasms, Esop... Esophageal Canc...	Nivolumab Entinostat Montanide(R) IS... H1299 Cell Lysa...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal Cancer	NCT05898828	Neoplasms Esophageal Neop... Esophagus Neopl... Esophagus Cance... Neoplasms, Esop... Esophageal Canc...	Nivolumab Entinostat Montanide(R) IS... H1299 Cell Lysa...	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)

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Spots Global Cancer Trial Database for esc

Every month we try and update this database with for esc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for esc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.