Co-stimulatory Markers and Vitamin D Status in Anti-PD1 Treated Melanoma Patients

NCT03197636 | Completed

• 1 other identifier: MSD-PD-1/vitD
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

An observational single center study designed to identify response-related biomarkers of anti-programmed death 1 (PD-1) therapy to advanced melanoma patients and to investigate if vitamin D levels are related to treatment response. 40 patients diagnosed with advanced melanoma will be included. Patients are included at the Department of Oncology, Aarhus University Hospital (AUH). All patients will be treated with Pembrolizumab as a standard procedure at the Department of Oncology. The protocol comprises blood samples at baseline, 3 and 6 weeks after treatment initiation with anti-PD1 therapy and three years of observational follow-up. A total amount of 217 ml blood will be drawn during the study period. The study period is 6 weeks followed by 3 years of follow-up. Medical history, symptoms, response to treatment regarding the RESIST criteria and side affects will be recorded at each visit in both the study period and in follow-up. Biochemical markers will be obtained according to normal procedure during study and follow-up visits. 20 Healthy volunteers (HV) are included, matched by age and gender. Collected blood samples (serum, plasma, peripheral blood mononuclear cells) will be analyzed after the last patient has ended the week 6 visit.

Conditions

Malignant Melanoma

Keywords

Vitamin D; Soluble PD-1

Outcome Measures

Primary Outcomes (1)

• Plasma levels of sPD-1

  Plasma levels compared to HC and correlation to disease outcome and vitamin D status (above or below the reference interval)

  1-2 years

Study Arms (2)

Malignant melanoma patients

40 patients with metastatic melanoma are included. Patients are admitted to Department of Oncology, Aarhus University Hospital (AUH). The patients are recruited to the study from the outpatient clinic of the Department of Oncology when they are about to begin treatment with pembrolizumab.

Drug: Pembrolizumab

Healthy controls

20 Healthy volunteers (HV) are included, matched by age and gender.

Interventions

Pembrolizumab DRUG

Pembrolizumab is already approved for treatment of malignant melanoma in advanced stages. We will investigate if sPD-1 or vitamin D status is changed in patients receiving pembrolizumab.

Malignant melanoma patients

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

40 patients with metastatic melanoma are included. Patients are admitted to Department of Oncology, Aarhus University Hospital (AUH). The patients are recruited to the study from the outpatient clinic of the Department of Oncology when they are about to begin treatment with pembrolizumab. Patients are informed that participation is voluntary and they can withdraw the informed consent at any time without a reason and without consequences.

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Be willing and able to provide written informed consent/assent for the trial.
• About to be treated with pembrolizumab as standard of care and first line treatment
• Be ≥ 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Ocular metastatic melanoma
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

AUH

Aarhus, 8000, Denmark

Location

Related Publications (3)

• Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, Cranmer LD, Blank CU, O'Day SJ, Ascierto PA, Salama AK, Margolin KA, Loquai C, Eigentler TK, Gangadhar TC, Carlino MS, Agarwala SS, Moschos SJ, Sosman JA, Goldinger SM, Shapira-Frommer R, Gonzalez R, Kirkwood JM, Wolchok JD, Eggermont A, Li XN, Zhou W, Zernhelt AM, Lis J, Ebbinghaus S, Kang SP, Daud A. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):908-18. doi: 10.1016/S1470-2045(15)00083-2. Epub 2015 Jun 23.

  PMID: 26115796 BACKGROUND

• Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007 Mar;8(3):239-45. doi: 10.1038/ni1443.

  PMID: 17304234 BACKGROUND

• Correale J, Ysrraelit MC, Gaitan MI. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain. 2009 May;132(Pt 5):1146-60. doi: 10.1093/brain/awp033. Epub 2009 Mar 24.

  PMID: 19321461 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood cells.

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

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

Study Officials

• Henrik Schmidt

  AUH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, DMSc

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: June 23, 2017
• Study Start: August 11, 2017
• Primary Completion: November 1, 2021
• Study Completion: February 1, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Locations

DK (1)