Ability of a Dendritic Cell Vaccine to Immunize Melanoma or Epithelial Cancer Patients Against Defined Mutated Neoantigens Expressed by the Autologous Cancer

NCT03300843 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 17017717-C-0177
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Exomes are the parts of deoxyribonucleic acid (DNA) that make proteins. Researchers are finding a way to read the letters in the exome. Incorrect letters are called mutations. Tumors contain specific mutations. Researchers can find these mutations in tumors to make treatments. Researchers want to use pieces of participants tumors to find the tumor-specific mutations. They also will take participants white blood cells to make a vaccine that they hope will shrink the tumors. Objectives: To see if dendritic vaccine tumor-fighting cells are safe and can cause certain cancer tumors to shrink. Eligibility: Adults ages 18-70 who have metastatic melanoma or metastatic epithelial cancer Design: The first part of this study was done under protocol 03-C-0277. In that study, white blood cells and pieces of participants' tumors were taken to make a vaccine. In this study, participants will get a vaccine every 2 weeks for 8 weeks. It will be given both in a vein and under the skin. At each visit, participants will have a physical exam and have blood taken. They will talk about any side effects they have. After treatment ends, participants will have many follow-up visits for the first year, then once each year after that. Visits will last up to 2 days each. They will include lab tests, imaging studies, and a physical exam. Blood will be taken at each visit. At the first follow-up visit, participants may have leukapheresis, which they also had as part of protocol 03-C-0277. Participants may not have to return to the Clinical Center for these visits.

Conditions

Melanoma; Gastrointestinal Cancer; Breast Cancer; Ovarian Cancer; Pancreatic Cancer

Keywords

Cell Therapy; Immunotherapy; Vaccines

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Had a Clinical Response (Complete Response (CR) + Partial Response (PR)) to Treatment

  Response was assessed by the RECIST v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  up to 6 months

Secondary Outcomes (2)

• Number of Participants With 2-3 Fold Increase From Baseline in Reactivity to Circulating Antigen-specific T Cells to the Mutated Peptide Compared to the Non-mutated Peptide

  Day 0, Day 14 (± 5 d), Day 28 (± 5 d), and Day 42 (± 5 d)

• Number of Participants With Serious and Non-serious Adverse Events

  Date treatment consent signed to date off study, approximately 6 months and 11 days

Study Arms (1)

Peptide loaded dendritic cell vaccine

EXPERIMENTAL

Peptide loaded dendritic cell vaccine on days 0, 14, 28, and 42

Biological: Peptide loaded dendritic cell vaccine

Interventions

Peptide loaded dendritic cell vaccine BIOLOGICAL

On days 0, 14 (+/- 5 days), 28 (+/- 5 days), and 42 (+/- 5 days). The vaccine will be administered as both an intravenous (IV) infusion and a subcutaneous (SQ) injection. The total dose will be divided equally between intravenous (IV) and SQ containing 1.0E7 to 8.0E7 cells per cycle depending upon the manufacturing yield.

Peptide loaded dendritic cell vaccine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic melanoma or epithelial cancer with at least one lesion that is resectable or in selected cases, available peripheral blood mononuclear cells (PBMCs)
• Measurable and evaluable metastatic disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Confirmation of the diagnosis of metastatic cancer by the Laboratory of Pathology of National Cancer Institute (NCI).
• All patients must be refractory to approved standard systemic therapy.
• Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
• Greater than or equal to 18 years of age and less than or equal to 70 years of age.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1, 2
• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
• Serology:
• Seronegative for Human Immunodeficiency Virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by reverse transcriptase polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
• Hematology
• Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim
• White blood cell (WBC) greater than or equal to 3000/mm\^3
• Platelet count greater than or equal to 100,000/mm\^3

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Active systemic infections (requiring anti-infective treatment), coagulation disorders or any other active or uncompensated major medical illnesses.
• Patients who are receiving any other investigational agents.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Klein L, Hinterberger M, Wirnsberger G, Kyewski B. Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol. 2009 Dec;9(12):833-44. doi: 10.1038/nri2669.

  PMID: 19935803 BACKGROUND

• Abramson J, Giraud M, Benoist C, Mathis D. Aire's partners in the molecular control of immunological tolerance. Cell. 2010 Jan 8;140(1):123-35. doi: 10.1016/j.cell.2009.12.030.

  PMID: 20085707 BACKGROUND

• Bos R, Marquardt KL, Cheung J, Sherman LA. Functional differences between low- and high-affinity CD8(+) T cells in the tumor environment. Oncoimmunology. 2012 Nov 1;1(8):1239-1247. doi: 10.4161/onci.21285.

  PMID: 23243587 BACKGROUND

MeSH Terms

Conditions

Melanoma; Gastrointestinal Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Breast Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases

Results Point of Contact

• Title: Dr. Steven A. Rosenberg
• Organization: National Cancer Institute

steven-rosenberg@nih.gov

240-858-3080

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: October 4, 2017
• Study Start: April 11, 2018
• Primary Completion: July 9, 2019
• Study Completion: September 16, 2019
• Last Updated: December 13, 2019
• Results First Posted: December 13, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)