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

Symptoms and General Pathology

Adenoma

Colonic Polyps

Polyps

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Pathological Conditions, Anatomical

Intestinal Polyps

All participants will be evaluated with the Colosense Test system and a colonoscopy.

The Colosense Collection Kit provides information on how to collect a stool swab using a fecal immunochemical test (FIT) and how to collect a stool sample using the Colosense Collection Kit. After a stool sample is produced, patients will swab the stool sample using the FIT tube according to instructions and return the stool sample via mail courier to Geneoscopy's Laboratories. Patients will then be directed to receive a colonoscopy. If a lesion is removed during the colonoscopy, the tissue sample will be sent for histopathology review. The colonoscopy report and the histopathology report will be reported to Geneoscopy. Stool samples returned to Geneoscopy's Laboratories will be subjected to the Colosense test system, which includes targeted nucleic acid enrichment and biomarkers quantification via droplet digital polymerase chain reaction. The FIT returned in the Colosense Collection Kit will also be read by laboratory technologists at Geneoscopy.

Colosense Stool Sample Collection Kit

Elizabeth Wurtzler, PhD

Faith Holmes, MD

This study will be a prospective analysis conducted by Geneoscopy Inc. to evaluate the Colosense test, which is a multi-target stool RNA test for colorectal screening.

Patients who are eligible for a colonoscopy (i.e., average risk individuals 45 years of age and older who are not up-to-date with screening guidelines) will be enrolled in the study. Stool samples returned to Geneoscopy's Laboratories by the participant will be subjected to the Colosense test system, and a result will be generated. The result will be compared to an optical colonoscopy to determine: 1) sensitivity for colorectal cancer, advanced adenomas, and other precancerous adenomas and 2) specificity for hyperplastic polyps and no findings on a colonoscopy. This study will be used for the clinical validation of the Colosense test.

This study will be a prospective analysis conducted by Geneoscopy Inc. to evaluate the Colosense test, which is a multi-target stool RNA test for colorectal screening. Patients who are eligible for a colonoscopy (i.e., average risk individuals between 45-80 who are not up-to-date with screening guidelines) will be enrolled in the study. Stool samples returned to Geneoscopy's Laboratories by the participant will be subjected to the Colosense test system, and a result will be generated. The result will be compared to an optical colonoscopy to determine: 1) sensitivity for colorectal cancer, advanced adenomas, and other precancerous adenomas and 2) specificity for hyperplastic polyps and no findings on a colonoscopy. This study will be used for the clinical validation of the Colosense test.

Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test Study

Clinical Validation of the ColonoSight Test: a Multi-target Stool RNA (Mt-sRNA) Assay for Colorectal Neoplasia Screening in Average-risk Individuals Aged >45 Years Old

Colosense sensitivity for subjects with CRC, which is the percentage of individuals with a diagnosis of colorectal cancer that were detected as positive by the ColonoSight test.

Colosense sensitivity for subjects with AA, which is the percentage of individuals with a diagnosis of advanced adenoma that were detected as positive by the Colosense test.

Colosense sensitivity for subjects with high-grade dysplasia, which is the percentage of individuals with a diagnosis of carcinoma in situ or advanced adenoma with high grade dysplasia that were detected as positive by the Colosense test.

Colosense sensitivity for subjects with Other Adenomas (OAs), which is the percentage of individuals with a diagnosis of a non-advanced precancerous adenoma that were detected as positive by the Colosense test.

Colosense specificity for subjects with negative findings, which is the percentage of individuals with a diagnosis of benign polyps, or no findings on a colonoscopy that were detected as negative by the Colosense test.

Geneoscopy, Inc.

Recurrence

Disease Attributes

Pembrolizumab

Vaccines

Molgramostim

Sargramostim

Immunologic Factors

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.

National Cancer Institute (NCI)

LabyRx Immunologic Therapeutics

Principal Investigator

Gastrointestinal Agents

Pancrelipase

Pancreatin

1250 mg/m2/d, IV (in the vein) on day 1, 8 and 15 of each 4 week cycle. Number of Cycles: until progression or unacceptable toxicity develops.

IV CP-4126

The main objective of this study is to assess the biological activity of CP-4126 in patients with advanced pancreatic cancer. In addition, the correlation between hENT1 (human equilibrative nucleoside transporter 1) and overall survival will be studied.

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
Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test Study	NCT04739722	Colorectal Canc... Advanced Adenoc... Adenoma Colon Polyp of Colon	Colosense Stool...	45 Years -	Geneoscopy, Inc.
Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test Study	NCT04739722	Colorectal Canc... Advanced Adenoc... Adenoma Colon Polyp of Colon	Colosense Stool...	45 Years -	Geneoscopy, Inc.
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
Colorectal Cancer and Pre-Cancerous Adenoma Non-Invasive Detection Test Study	NCT04739722	Colorectal Canc... Advanced Adenoc... Adenoma Colon Polyp of Colon	Colosense Stool...	45 Years -	Geneoscopy, Inc.
A Study of CP-4126 in Patients With Advanced Pancreatic Cancer	NCT00913198	Advanced Adenoc...	IV CP-4126	18 Years -	Clavis Pharma

Spots Global Cancer Trial Database for advanced adenocarcinoma