Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Gemcitabine

Paclitaxel

Hydroxychloroquine

Albumin-Bound Paclitaxel

Antimetabolites

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Abraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15 Hydroxychloroquine: 1200 mg/day PO daily (600mg BID) Daily from D1

Abraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15

Hydroxychloroquine (HCQ)

Abraxane

Peter O'Dwyer, MD

In this Phase I/II clinical trial, the investigators seek to pilot the addition of Hydroxychloroquine (HCQ) to a commonly-used front-line therapy of pancreatic cancer, gemcitabine/nab-paclitaxel. The investigators plan a run-in to define tolerable doses, and will explore doses of 800 and 1200 mg/day in successive cohorts of 6 patients. The investigators will assess toxicity continuously, and determine the dose for the Phase II trial based on standard toxicity criteria.

The correlative endpoints of this trial are directed to the pharmacokinetics of HCQ, and pharmacokinetic model of HCQ based on data from several ongoing trials, and the data from these patients will contribute to refining the model. The investigators will analyze both measured and model-predicted indices for their relationship to autophagy induction. Autophagy will be assessed as the accumulation of autophagocytic vesicles in the PMNs of treated patients, together with the induction of the expression of autophagy-related proteins on western analysis, quantitated by densitometry. The investigators will document the rates of metabolic response as a consequence of treatment, as a therapeutic marker that may be related to the degree of autophagy inhibition. Since the investigators have previously demonstrated a key role of JNK1 in the induction of autophagy by chemotherapy, the investigators will analyze archival tumor materials to determine variability in this marker, as a baseline for potential future trials. Finally, this study will incorporate metabolic profiling by mass spectrometry, which will be related to mutations (including Kras) in pretreatment tumor specimens. Mutational analysis will be accomplished by targeted sequencing or by next-generation sequencing, and the need for fresh tissue for all these endpoints will require patients to have a biopsy performed before treatment at at 6-8 weeks after beginning treatment. In the previous study of the Hh inhibitor GDC-0973 with the same chemotherapy, the investigators were able to obtain repeat biopsies successfully on all patients. The importance of these biopsies, to move the science forward in an era in which the tools now exist to provide meaningful correlative science, cannot be overstated.

Recent strategies have focused on improving the efficacy of gemcitabine either by improving the method of delivery, or by combining gemcitabine with other non-cross resistant agents. A sequence of Phase III combination studies of gemcitabine in combination (with oxaliplatin, and with the targeted therapies bevacizumab and cetuximab) have been negative, though based on strikingly positive Phase II data generated in cancer centers. Several studies suggest that taxanes are active in pancreatic cancer, but a randomized trial of gemcitabine with taxanes has not been preformed, probably on the basis that the differences in Phase II were insufficiently persuasive. The development of a novel taxane conjugate with albumin, abraxane, with established activity in breast cancer, prompted a Phase II trial of gemcitabine/abraxane by Von Hoff (6). Phase I/II data were highly promising, with response rates of the order of 40%, with tolerable toxicity, and a one-year survival of about 48%. A phase III trial of gemcitabine versus gemcitabine/abraxane is in progress, and based on these promising data has served as the control chemotherapy for previous SU2C trials. The development of a more intensive, but toxic regimen (FOLFIRINOX) in no way diminishes the enthusiasm for this chemotherapy backbone, given the activity in Phase II trials that appears comparable (7). Given the promise of this regimen, and the possibility of making a substantial improvement in outcome with additional targeted interventions, we propose to continue to use this regimen in the current study.

Of particular interest in extending these studies to pancreatic cancer is the finding that autophagy inhibition is particularly deleterious to cell lines bearing a mutant Kras protein. Additional studies as part of the SU2C pancreatic cancer project reveal that an autophagy program is activated in the presence of mutant Kras, and thus prompts the testing of this strategy in a setting in which Kras is commonly (about 85%) mutated (SU2C, unpublished data).

A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer

Abramson Cancer Center at Penn Medicine

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Capecitabine

Cisplatin

The trial will compose of 2 parts with a total of 40 subjects. The regimen will consist of gemcitabine (G) administered at a dose of 800 mg/m2, cisplatin (C) 30 mg/m2, and protein-bound paclitaxel (N) 150 mg/m2 administered on cycle 1 day 1 and every 2 weeks thereafter and TTF will be administered daily (150kHz 18 hours/day) starting with Cycle 1 Day 1 (dose level 1). After completing 6 cycles, patients will then transition to a maintenance phase of G administered at a dose of 1000 mg/m2 every 2 weeks and daily TTF (150 KHZ 18 hours/day) until progression of disease (POD) per RECIST v1.1. If 6 patients tolerate the dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).

The regimen will consist of gemcitabine (G) administered at a dose of 800 mg/m2, cisplatin (C) 30 mg/m2, and protein-bound paclitaxel (N) 150 mg/m2 administered on cycle 1 day 1 and every 2 weeks thereafter and TTF will be administered daily (150kHz 18 hours/day) starting with Cycle 1 Day 1 (dose level 1). One cycle consists of 28 days including 2 chemotherapy treatments (same regimen studied in the PAXG trial: Reni BJC 2016 without capecitabine). After completing 6 cycles, patients will then transition to a maintenance phase of G administered at a dose of 1000 mg/m2 every 2 weeks and daily TTF (150 KHZ 18 hours/day) until progression of disease (POD) per RECIST v1.1.

Modified GCN+TTF treatment

Clinical Trials Referral Office

Hani M. Babiker, M.D.

This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with Tumor Treatment Fields (TTF) and G+TTF maintenance therapy in patients with metastatic pancreatic cancer.

GCN is predicted to be the front-line therapy for biliary and pancreatic cancer in the future given excellent results of current early clinical trials (ORR ≥ 67% in pancreatic cancer). This will change standard of care for front-line therapy in patients with stage IV pancreatic cancer. In this cohort of patients' tolerability after 6 cycles of therapy will be a challenge. Investigators hypothesize that developing a maintenance strategy with TTF+G will be cutting edge approach and can potentially transform front-line standard of care therapy in patients with stage IV pancreatic cancer. If this pilot study proves fruitful then a larger study to confirm findings can be conducted.

The trial will compose of 2 parts with a total of 40 subjects. The 1st part would be a safety run-in phase (phase I). In this phase, 6 patients will be treated after completing screening procedures and meeting eligibility criteria. If 6 patients tolerate this dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).

Nab-Paclitaxel + Cisplatin + Gemcitabine + TTF in pt. w/ Metastatic PAC

A Phase I/Ib Pilot Trial, Single Arm, Open Label, of Protein-Bound Paclitaxel, Cisplatin, and Gemcitabine (GCN) Combined With Tumor Treatment Fields (TTF) in Patient With Metastatic Pancreatic Adenocarcinoma

To determine the safety of modified (m)-GCN+TTF in patients with recurrent and/or metastatic pancreatic cancer (met-PC) by measuring grade 4 treatment related adverse events (TRAE).

Objective responses in tumor size will be evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).

NovoCure Ltd.

Mayo Clinic

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Infections

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Vaccinia

Fowlpox

Ovarian Cancer

Ovarian Epithelial Cancer

Vaccines

Molgramostim

Sargramostim

Immunomodulating Agents

Immunologic Factors

All cohorts receive the same intervention (Cohort 1: Colorectal arm, non-colorectal cancers; Cohort 2: breast cancer; Cohort 3: ovarian cancers)

Patients receive 2 x 10(8) pfu PANVAC-V (vaccinia) subcutaneously on Day 1.

PANVAC-V

Patients receive 1 x 10(9) pfu PANVAC-F (fowlpox) or about days 15, 29, and 43 then every month for 12 doses then every 3 months until disease progression or toxicity.

PANVAC-F

100g sargramostim will be given subcutaneously at the site of the vaccination on each vaccination day and for three consecutive days thereafter.

Sargramostim (GM-CSF, Leukine)

James L Gulley, M.D.

Background:

* Many cancers produce two proteins, carcinoembryonic antigen (CEA) and mucin-1 (MUC-1).
* The PANVAC-V (PANVAC vaccinia) priming vaccine and PANVAC-F (PANVAC fowlpox) boosting vaccine contain human genes that cause production of CEA and MUC-1, which can be used as a target for the immune system to attack the cancer. The vaccines also contain genes that cause production of other proteins that enhance immune activity.
* Sargramostim is a protein that boosts the immune system.

Objectives:

* To evaluate the safety and effectiveness of PANVAC-V and PANVAC-F in patients with advanced cancer.
* To document the immune response to the vaccines and any anti-tumor responses that may occur.

Eligibility: Patients 18 years of age and older with advanced cancer whose tumors produce CEA or MUC-1 protein

Design:

* This trial has three cohorts: the first cohort includes 10 patients with advanced colorectal cancer and 10 to 15 patients with any advanced non-colorectal cancer that produces either EA or mitochondrial Ca2+ uniporter 1 (MCU-1); the second cohort includes 12 patients with advanced breast cancer and the third cohort includes 14 patients with advanced ovarian cancer.
* All patients receive PANVAC-V on study day 1, followed by PANVAC-F on days 15, 29 and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity. The vaccines are given by injection under the skin. Sargramostim is injected at the vaccination site on the day of each vaccination and for the next 3 days following vaccination.
* Patients whose scans show that their disease has progressed, but who are otherwise clinically stable may revert back to monthly injections.
* Patients undergo apheresis to collect white blood cells (lymphocytes) on day 1 and day 71 of the study to measure the immune response to the treatment. Blood is collected through a needle placed in one arm and directed through a cell separator machine where the lymphocytes are extracted. The rest of the blood components are returned to the patient through the same needle.
* Patients are monitored with frequent blood tests and periodic imaging tests (scans) to monitor for safety and the response to treatment.

Background:

* Carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) are overexpressed in multiple adenocarcinomas.
* Pox viral vectors can induce a strong immune response to CEA and MUC-1.
* The use of agonist epitopes within the tumor associated antigen (TAA) can induce a better immune response than native peptides and have been associated with clinical responses
* Heterologous prime and boost regimens are superior in terms of generalizing immune responses; and this may translate into improved clinical responses
* The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) does not add significant toxicity and in pre-clinical models is essential for induction for optimal immune responses.
* It is possible by using vectors directed against TAA that there may be additive or synergistic immune responses and this may be important in overcoming antigenic escape variance
* Evidence of clinical benefit has been noted in some patients treated with this vaccine

Objectives:

* For colorectal cancer and non-colorectal cancer Cohort: To evaluate the safety and tolerability of the vaccine.
* For the Ovarian Cancer and Breast Cancer Cohorts: To evaluate clinical response to the vaccine.

Eligibility:

* In the first cohort (colorectal and non-colorectal cancer), histologically confirmed adenocarcinoma that is CEA or MUC-1 positive described as metastatic disease (measurable or evaluable) or metastatic disease documented by biopsy but not evaluable by imaging (e.g. small volume peritoneal disease)
* For the ovarian and breast cancer cohorts, patients must have evaluable disease
* Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-1

Design:

* This is a non-randomized three cohort, pilot trial of pox viral vaccines that contain the transgenes for CEA and MUC-1 (both with modified human leukocyte antigen A2 (HLA-A2) agonist epitopes) as well as 3 human T-cell costimulatory molecules, B7-1, ICAM-1 (CD54), and LFA-3 (CD58) \[PANVAC(TM)-V (vaccinia) and PANVAC(TM)-F (fowlpox)\] in patients with metastatic carcinoma that express CEA or MUC-1 antigen.
* The first cohort will enroll 10 patients with metastatic colorectal adenocarcinoma and 10-15 patients with any metastatic non-colorectal carcinoma that expresses either CEA or MUC-1. .
* The second cohort will enroll 12 patients with metastatic breast carcinoma and 14 patients with metastatic ovarian carcinoma.
* All patients will receive the same vaccines on the same schedule. PANVAC(TM)-V (vaccinia) subcutaneously (s.c.) scheduled on day 1, followed by PANVAC(TM)-F (fowlpox) s.c. scheduled on days 15, 29, and 43 then every 28 days for up to 12 vaccines followed by every 3 months until disease progression or toxicity.
* Sargramostim (100 micro g) will be given at the site of the vaccination (PANVAC-V and PANVAC-F) on each vaccination day and for three consecutive days thereafter.
* Patients who have radiographic evidence of progressive disease, but who are otherwise clinically stable may revert back to monthly vaccinations.

PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer

An Open Label Pilot Study to Evaluate the Safety and Tolerability of PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) in Combination With Sargramostim in Adults With Metastatic Carcinoma

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all clinical and laboratory signs and symptoms of disease for a minimum of 4 weeks during which no new lesions may appear. Partial Response is a minimum of 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Stable disease is neither sufficient shrinkage to qualify for partial response nor progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions.

Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Vaccines were administered to participants and Grade 1 (mild) and Grade 2 (moderate) adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. Common Terminology Criteria in Adverse Events. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 if reported prior to August 1, 2010 and CTCAE v4.0 if reported after. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Immune response in human leukocyte antigens (HLA)-A2 positive patients to carcinoembryonic antigen (CEA) was assessed by enzyme-linked immunospot assay (ELISPOT) analysis. A positive immune response was defined as a \>2x fold increase in the number of interferon gamma producing cells.

National Cancer Institute (NCI)

Principal Investigator

Adverse events were assessed by the Common Terminology Criteria in Adverse Events(CTCAE)\*v3.0 if reported prior to August 1, 2010 and CTCAE \*v4.0 if reported after.

Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (\>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.

Colorectal Cancer vs Non-Colorectal Cancer Cohort

Patients with evaluable, metastatic breast or ovarian cancer who have failed or not a candidate for standard therapy.

Breast and Ovarian Cohorts

Patients with histologically confirmed measurable or evaluable colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (\>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.

Colorectal Cancer Cohort

Patients with histologically confirmed measurable or evaluable metastatic non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (\>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.

Non-Colorectal Cancer Cohort

Patients with evaluable, metastatic breast cancer who have failed or not a candidate for standard therapy.

Breast Cohort

Patients with evaluable, metastatic ovarian cancer who have failed or not a candidate for standard therapy.

Ovarian Cohort

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Hispanic or Latino

Not Hispanic or Latino

Asian

Black or African-American

White

Unknown or Not Reported

Race/Ethnicity, Customized

United States

Region of Enrollment

Grade 0

Grade 1

Grade 0 is normal activity. Fully active, able to carry on all pre-disease performance without restriction. Grade 1 is symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework, office work).

Number of Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0-1

No prior chemotherapy

Chemotherapy (1 regimen)

Chemotherapy (2 regimens)

Chemotherapy (≥3 regimens)

Radiation

Number of Participants with Prior Therapy

Colorectal

Gastric

Pancreatic

Appendiceal

Esophageal adenocarcinoma

Ovarian

Breast

Lung

Number of Participants with a Primary Tumor

Dr. James Gulley

Complete Response

Partial Response

Stable Disease

Progressive Disease

Breast Cancer Cohort

Ovarian Cancer Cohort

Number of Participants With Complete Responses (CRs), Partial Responses (PRs,) Stable Disease and Progressive Disease in the Ovarian Cancer and Breast Cancer Cohorts

Injection-site reaction

Fatigue

Fever

Hemoglobin/Anemia

Hypoalbuminemia

Alk Phos

Syncope

Anorexia

Vomiting

Hot flushes/flashes

Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer, non-colorectal cancer or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (\>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.

Colorectal Cancer and Non-Colorectal Cancer Cohort

The colorectal and non-colorectal cohorts received the same treatment on the same schedule, had no immune dysfunction at baseline and are biologically equivalent. For rare events in small cohorts, a better estimate of the true event rate is determined by grouping similar patients and is consistent with the peer-reviewed clinical paper.

Percentage of Vaccines Associated With Grade 1 and Grade 2 Adverse Events Related to Vaccine in the Colorectal Cancer and Non-Colorectal Cancer Arm/Group

Musculoskeletal pain

Anemia

Breast Cancer and Ovarian Cancer Cohorts

The breast and ovarian cohorts received the same treatment on the same schedule, had no evidence of immune dysfunction at baseline and are biologically equivalent. For rare events that occur in small trial arms, the true event rate is better determined by grouping similar patients and is consistent with the peer-reviewed clinical paper.

Percentage of Participants With Grade 1 and Grade 2 Adverse Events Possibly, Likely, or Definitely Related to Vaccine in the Breast Cancer and Ovarian Cancer Cohorts

Patients with histologically confirmed measurable or evaluable metastatic colorectal cancer, non-colorectal cancer, or patients with surgically resected metastatic disease at high risk for recurrence who had completed at least one 5-fluorouracil/(5-FU) containing chemotherapy regimen (e.g., 5-fluorouracil/leucovorin (5-FU/LV) with or without either irinotecan or oxaliplatin or patients that have had an elevated serum CEA (\>5 ugg/L) at any point during their disease course who have failed or not a candidate for standard therapy.

Patients with evaluable, metastatic breast cancer or ovarian cancer who have failed or not a candidate for standard therapy.

Breast Cancer and Ovarian Cancer Cohort

Pts in these 2 cohorts rec'd the same treatment, have absence of immune dysfunction at baseline and are biologically equivalent. For rare events that occur in small cohorts, a better est. of the true event rate can be determined by grouping the pts in the absence of a biological rationale and is consistent with the peer-reviewed clinical paper.

Number of Participants With Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE) v3.0 and v4.0

Overall number of participants analyzed reflects participants that are HLA-A2 positive.

Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Colorectal Cancer and Non-colorectal Cancer Cohort Post Vaccination

Only 3 Breast Cancer and 2 Ovarian Cancer patients had enough blood collected to perform enzyme-linked immunospot (ELISPOT) analysis.

Number of Participants With an Positive Immune Response to Carcinoembryonic Antigen (CEA) Peptide and/or Protein in the Breast Cancer and Ovarian Cancer Cohorts Post Vaccination

Overall Study

Symptoms and General Pathology

Recurrence

Disease Attributes

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive sargramostim SC and LabVax 3(22)-23 ID on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity.

Pembrolizumab will be given intravenously every 3 weeks for up to 12 cycles on Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, and 34. Participants will be given LabVax 3(22)-23 (intradermally) and adjuvant GM-CSF (subcutaneously) on weeks 7, 8, 10, 14, and 18.

Antineoplastic Vaccine

Selina Laqui

Tianhong Li

This phase 1/2 trial tests the safety and effectiveness of a cancer vaccine called Labvax 3(22)-23 and GM-CSF alone or in combination with pembrolizumab in treating adenocarcinoma that has spread to other places in the body (advanced stage). Labvax 3(22)-23 is designed to target a specific antigen (labyrinthin), which is a protein found on the surface of adenocarcinoma tumor cells. Labyrinthin is a protein that is not expressed on normal cells in the skin, lungs, salivary glands, pancreas, nor other tissues. In adenocarcinoma, the tumor cells produce too much labyrinthin causing them to express this protein on the surface of the tumor cells. One way to control the growth of these tumor cells is to teach the immune system to generate an immune response against the labyrinthin protein by vaccination against labyrinthin. GM-CSF, or sargramostim, is a protein that acts as a white blood cell growth factor. It has also been shown to stimulate immune system. Thus, administration of GM-CSF may help to boost the immune system response when given together with the vaccine. This study may improve the general knowledge about Labvax 3(22)-23 and how the body may generate an immune response to kill adenocarcinoma tumor cells. In the second phase of the study, participants will also receive pembrolizumab, which may improve anti-cancer activity when given with Labvax 3(22)-23 and GM-CSF.

Phase 1: Up to 10 participants with advanced/ metastatic or recurrent adenocarcinoma of any primary site will be enrolled. Participants will be given LabVax 3(22)-23 (intradermally) and adjuvant GM-CSF (subcutaneously) on weeks 1, 2, 4, 8, and 12. Participants will be evaluated for 16 weeks, which include a follow-up exam 4 weeks after the last injection of vaccine or last injection, if injection(s) are stopped earlier. The study will be terminated if one death or two subjects have ≥3 adverse events that are at least possibly related to the study treatment. \[Note: Phase 1 enrollment was completed as of December 2022\]

Phase 2: Up to 67 participants with advanced/ metastatic or recurrent lung adenocarcinoma (Cohort A) or non-lung adenocarcinomas (Cohort B). Pembrolizumab will be given intravenously every 3 weeks for up to 12 cycles on Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, and 34. Subjects will be given LabVax 3(22)-23 (intradermally) and adjuvant GM-CSF (subcutaneously) on weeks 7, 8, 10, 14, and 18. Participants will receive study treatment over 34 weeks if tolerating the treatment without tumor progression; a safety follow-up visit will occur 30 days post-last dose of study treatment. The participant's chart will be reviewed for up to 12 months post-last dose of study treatment. The study will be terminated if safety is insufficient following the lead-in period or if response is insufficient in Cohort A following the first expansion.

A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma

A Phase 1/2 Open Label Study of LabVax 3(22)-23 and Adjuvant GM-CSF Alone or in Combination With Pembrolizumab in Subjects With Labyrinthin-Positive Adenocarcinomas

Will be assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0. The type, grade, frequency and proportion of toxicities noted during the treatment period will be reported, along with associated 95% two-sided exact confidence interval of proportion. All adverse events noted by the investigator will be tabulated according to the affected body system.

Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V)1.1 guidelines. The fractions will be reported along with 95% two-sided exact confidence intervals. Comparisons between arms will be performed by Fisher's Exact tests. Investigators will also characterize the proportion who remain that either respond or have stable disease, compared to those who progress.

PFS will be calculated as the time from initiation of immunotherapy to first documented evidence of disease progression or death, whichever comes first. Alive patients who have not been documented to have progression will be censored at the date of the latest clinical assessment that documented as being free of progression.

OS will be calculated as the time from diagnosis to death. Alive patients will be censored at the date of the latest follow-up visit.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer	NCT01506973	Advanced Adenoc... Metastatic Aden...	Hydroxychloroqu... Gemcitabine Abraxane	18 Years -	Abramson Cancer Center at Penn Medicine
Nab-Paclitaxel + Cisplatin + Gemcitabine + TTF in pt. w/ Metastatic PAC	NCT04605913	Pancreas Cancer Metastatic Panc... Pancreatic Aden... Metastatic Aden...	Modified GCN+TT...	18 Years -	Mayo Clinic
PANVAC-V and PANVAC-F Vaccines Plus Sargramostim to Treat Advanced Cancer	NCT00088413	Adenocarcinoma Colorectal Canc... Ovarian Cancer Breast Cancer	PANVAC-V PANVAC-F Sargramostim (G...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone or in Combination With Pembrolizumab for the Treatment of Advanced Stage Adenocarcinoma	NCT05101356	Advanced Adenoc... Advanced Malign... Metastatic Aden... Metastatic Mali... Recurrent Adeno... Recurrent Malig...	Antineoplastic ... Sargramostim Pembrolizumab	18 Years -	University of California, Davis

Spots Global Cancer Trial Database for metastatic adenocarcinoma