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Sargramostim (GM-CSF) + PD-1

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ClinicalTrials.gov Identifier: NCT04703426
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
Partner Therapeutics (PTx)
Information provided by (Responsible Party):
Elizabeth Buchbinder, Dana-Farber Cancer Institute

Brief Summary:

This research study is testing the combination of two drugs, sargramostim and pembrolizumab. The study is designed to see if the combination of these study drugs would improve the control of unresectable or metastatic melanoma cancer when compared to use of these drugs alone.

The names of the study drugs involved in this study are:

  • Pembrolizumab
  • Sargramostim (GM-CSF)

Condition or disease Intervention/treatment Phase
Unresectable Melanoma Metastatic Melanoma Stage III Melanoma Stage IV Melanoma Drug: Sargramostim (GM-CSF) Drug: Pembrolizumab (anti-PD-1) Phase 2

Detailed Description:

This is an open-label phase II study looking at safety and efficacy of the combination of pembrolizumab (PD-1 inhibition and sargramostim (GMCSF) in people with unresectable stage III or IV melanoma who have not received prior immunotherapy in the metastatic setting.

The U.S. Food and Drug Administration (FDA) has not approved sargramostim as a treatment option for people with stage III or IV melanoma who have not received prior immunotherapy in the metastatic setting.

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab as a treatment option for people with stage III or IV melanoma who have not received prior immunotherapy in the metastatic setting.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

Participants will receive the study drug(s) for as long as they do not have serious side effects and their disease does not get worse and will be followed for safety 30 days after the last dose of study drug(s). Participants may also be followed for long term follow-up every 12 weeks from the last dose of study drug(s).

It is expected that about 30 people will take part in this research study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Copy of A Phase II Trial of Pembrolizumab (Anti PD-1) Therapy Combined With Sargramostim (GM-CSF) in Unresectable or Metastatic Melanoma
Actual Study Start Date : April 16, 2021
Estimated Primary Completion Date : June 10, 2022
Estimated Study Completion Date : June 9, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Sargramostim (GM-CSF) + Pembrolizumab (anti-PD-1)

Participants will receive 12 weeks of sargramostim (GM-CSF) and pembrolizumab (anti-PD-1). Participants may be pre-medicated with drugs to reduce the chance of having a sensitivity reaction to the study treatment of pembrolizumab (anti-PD-1) and sargramostim (GM-CSF).

Study cycles are 21 days in length:

  • Pembrolizumab (anti-PD-1) will be given by intravenous infusion once on day 1 of every 21 day cycle
  • Sargramostim (GM-CSF) will be self-administered by participants via a subcutaneous (below the skin) injection daily for days 1 - 14 of each 21- day cycle.

Participants will be assessed at 12 weeks for disease response/progression and further study treatment.

Drug: Sargramostim (GM-CSF)
Drug that binds to the protein PD-1 to help immune cells kill cancer cells better, it is given as an intravenous injection through a vein.
Other Name: Leukine

Drug: Pembrolizumab (anti-PD-1)
Drug that stimulates blood cells that may help support the immune system during cancer treatment, given as intravenous infusion
Other Name: Keytruda




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 12 weeks ]
    The primary study endpoint is response rate per RECIST criteria.


Secondary Outcome Measures :
  1. Number of Participants With Treatment-Related Adverse Events [ Time Frame: 12 weeks ]
    Number and proportion of adverse events, graded as defined by CTCAE version 5.0

  2. Overall Survival Rate [ Time Frame: 12 weeks ]
    Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) will be used.

  3. Progression Free Survival Rate [ Time Frame: 12 weeks ]
    Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) will be used.

  4. Overall Response Rate (ORR)-irRC [ Time Frame: 12 weeks ]
    To evaluate the overall response rate in advanced melanoma to combination anti- PD-1 therapy and sargramostim by irRC criteria.

  5. CD4+ ICOS T cell changes [ Time Frame: 12 weeks ]
    Evaluate changes in CD4+ ICOS T cells from biopsies (pre-treatment, on-treatment, post-treatment) and correlate using Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic diagnosis of metastatic or unresectable stage III or IV cutaneous melanoma
  • Age ≥ 18 years.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
  • Participants must have normal organ and marrow function as defined below:

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    • creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Measurable disease (by CT, PET/CT or MRI)
  • The effects of GMCSF and PD-1 inhibition on the developing human fetus are unknown.

For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration.

  • No prior immunotherapies in the metastatic setting. Prior targeted therapy is allowed.

For patients who have received adjuvant checkpoint inhibition they must have been off of therapy for ≥ 6 months at the time of progression

  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Participants who are receiving any other investigational agents.
  • Participants with known brain metastases must have documented stability over a four week interval and not be requiring active treatment for these. Prior radiation, surgery and stereotactic radiosurgery are allowed but must be completed four weeks prior to initiating therapy.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pembrolizumab or sargramostim.
  • Need for systemic steroids at the time of enrollment. Physiologic replacement at a dose of less than 10mg daily prednisone equivalent is allowed.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participants who are considered Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test in order to be eligible. Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Pembrolizumab, breastfeeding should be discontinued if the mother is treated with Pembrolizumab. These potential risks may also apply to other agents used in this study.
  • Known active HIV, Hepatitis B or Hepatitis C patients. HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for an immunologic effect with the therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Autoimmune disease that requires treatment at the time of enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04703426


Contacts
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Contact: Elizabeth Buchbinder, MD 617-632-5055 Elizabeth_Buchbinder@dfci.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Donald Lawrence, MD    617-724-4000    dplawrence@partners.org   
Principal Investigator: Donald Lawrence, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Elizabeth Buchcinder, MD    617-632-5055      
Principal Investigator: Elizabeth Buchbinder, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Partner Therapeutics (PTx)
Investigators
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Principal Investigator: Elizabeth Buchbinder, MD Dana-Farber Cancer Institute
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Responsible Party: Elizabeth Buchbinder, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT04703426    
Other Study ID Numbers: 20-370
First Posted: January 11, 2021    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Elizabeth Buchbinder, Dana-Farber Cancer Institute:
Unresectable Melanoma
Metastatic Melanoma
Stage III Melanoma
Stage IV Melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Sargramostim
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs