Metastatic MelanomaPhase 2NCT04987996
GR-MD-02 + Pembrolizumab Versus Pembrolizumab Monotherapy in Melanoma and Squamous Cell Head and Neck Cancer Patients
A Phase 2 study testing GR-MD-02 and Pembrolizumab in people with Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma, run by Providence Health & Services at 1 site in United States.
Trial summary
The purpose of this study is to test the safety \& efficacy of combination drugs versus placebo to treat metastatic melanoma and head and neck squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- GR-MD-02 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2023to 1 Jul 2031
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with unresectable or metastatic melanoma including unknown primary, mucosal or uveal melanomas. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy are eligible. PD-L1 testing is not needed for OHN cancers.
- Patients who have received anti-PD1 or anti-PD-L1 in the past are eligible if it has been at least 6 months since the last anti-PD-1 or PD-L1 dose, they meet all other eligibility criteria and progression of malignancy has been documented on imaging. Progression for this patient subset is defined as the appearance of one or more new metastatic sites, or a 5% or greater increase in the sum of diameter of target lesions or an unequivocal increase in non-target site. Treatment naïve melanoma patients are eligible.
- Patients must be ≥ 18 years of age.
- ECOG performance status of 0-2.
- Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy.
- No active bleeding.
- Anticipated lifespan greater than 12 weeks.
- Patients must sign a study-specific consent document.
Who cannot join
- Patients who have previously received a galectin antagonist.
- Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo (see Appendix C).
- Patients with history of autoimmune colitis.
- Patients with untreated brain metastases. Patients with treated brain metastases who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible.
- Patients requiring other systemic oncologic therapy, including experimental therapies.
- Patients with active infection requiring antibiotics.
Show all 20Show fewer
- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
- Need for steroids at greater than physiologic replacement doses. Inhaled corticosteroids are acceptable.
- Laboratory exclusions (to be performed within 28 days of enrollment):
- WBC < 3.0 x 109/L
- Hgb < 9.0 g/dL
- AST or ALT > 1.5 times ULN
- Total bilirubin > 1.9 g/dL, unless due to Gilbert's Syndrome. If Gilbert's Syndrome is present by clinical history, then direct bilirubin must by < 3.0 g/dl.
- Known history of HIV
- Known history of Hepatitis B
- Known history of Hepatitis C
- INR > 1.5x ULN
- Inability to give informed consent and comply with the protocol. Patients must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy.
- Any medical condition that in the opinion of the Principal Investigator would compromise the safety or conduct of the study procedures.
- Unresolved immune-mediated pneumonitis, diarrhea, elevation of hepatocellular enzymes or other toxicities requiring greater than physiological replacement doses of steroids.
Trial locations and contacts
1 site in 1 country.
United States1 site
Portland Providence Medical Center
Portland, Oregon, 97213
About this study
Official title: Randomized Double-Blind Placebo Controlled Phase II Study of a Galectin Inhibitor (GR-MD-02) and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma
The purpose of this study is to test the safety \& efficacy of combination drugs versus placebo to treat metastatic melanoma and head and neck squamous cell carcinoma.
Read the detailed description
Eligible patients will be registered, stratified by diagnosis (melanoma versus OHN cancer), and the number of prior systemic therapies, and randomized to receive either GR-MD-02 + pembrolizumab or pembrolizumab + placebo.
In addition to monitoring for toxicity and clinical response, blood and tumor samples will be obtained to assess immunologic measures relevant to galectin biology and pembrolizumab T-cell checkpoint inhibition.
- Being tested
- GR-MD-02, Placebo, Pembrolizumab
- Keywords
- HNSCC, MM, pembrolizumab, GR-MD-02, Galectin Inhibitor, GRMD-02, GRMD002
- Medical subject headings
- Melanoma, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GR-MD-02Drug
Also called Galactoarabino-rhamnogalactouronate
Patients will receive up to seventeen doses of GR-MD-02 intravenously over 85 Days.
PlaceboDrug
Patients will receive up to seventeen doses of placebo intravenously over 85 Days.
PembrolizumabDrug
Also called Keytruda
Patients will receive 200mg doses of pembrolizumab intravenously over 85 Days.
| Study group | Role | What they receive |
|---|---|---|
| GR-MD-02 + pembrolizumab | Experimental | 4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. Receives: Drug: GR-MD-02; Drug: Pembrolizumab |
| Pembrolizumab Monotherapy | Placebo comparator | 4 mg/kg placebo in combination with standard pembrolizumab treatment. Receives: Drug: Placebo; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate based on disease imaging
Determine the objective response of GR-MD-02 + pembrolizumab versus pembrolizumab monotherapy in patients with advanced MM or HNSCC
Measured: From date of randomization until the date of first documented progression, assessed up to 63 weeks.
Secondary outcomes (6)
Evaluation of GAL-3 expression
Compare GAL-3 expression in paired biopsies after GR-MD-02 + pembrolizumab or pembrolizumab monotherapy.
Measured: Screening and Day 68
Evaluation of predictive biomarker
Characterize MDSC expression over time as a predictive biomarker of response after GRMD02 + pembrolizumab or pembrolizumab monotherapy
Measured: Day 85
Frequency of Immune-mediated adverse events
Compare the frequency of immune-mediated adverse events after GR-MD-02 + pembrolizumab versus pembrolizumab + placebo
Measured: From time of informed consent to week 63
Evaluation of antiviral immunity
Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring CD4+T cells with a memory phenotype (CD3+CD4+Ki67+CD25+FoxP3-CCR7-CD45RA-CD27+CD28+/-).
Measured: Day 85
Evaluation of antiviral immunity
Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring CD8+ T cells with effector phenotype (CD3+CD8+CD28-CD95+).
Measured: Day 85
Evaluation of antiviral immunity
Assess the biological activity of GR-MD-02 + pembrolizumab and in comparison to pembrolizumab monotherapy by measuring tumor-specific T cells using autologous and/or HLA-matched tumor when available.
Measured: Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start1 Jul 2023 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2031 (estimated)
Why it stopped: Study withdrawn due to lack of supply of one of the investigational agents.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Providence Cancer Center, Earle A. Chiles Research Institute
- Responsible party
- Sponsor
- Investigators
- Brendan D. Curti, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04987996
- Sponsor's protocol ID
- 2020000655
- Status last verified
- Jun 2023
- First submitted
- 14 Jul 2021
- Last updated
- 6 Jun 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Double-Blind Placebo Controlled Phase II Study of a Galectin Inhibitor (GR-MD-02) and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04987996
- Acronym / sponsor ID
- 2020000655
- Keywords
- HNSCC, MM, pembrolizumab, GR-MD-02, Galectin Inhibitor, GRMD-02, GRMD002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn due to lack of supply of one of the investigational agents.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Providence Cancer Center, Earle A. Chiles Research Institute
- Study start
- 1 Jul 2023 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety \& efficacy of combination drugs versus placebo to treat metastatic melanoma and head and neck squamous cell carcinoma.
Detailed description
Eligible patients will be registered, stratified by diagnosis (melanoma versus OHN cancer), and the number of prior systemic therapies, and randomized to receive either GR-MD-02 + pembrolizumab or pembrolizumab + placebo.
In addition to monitoring for toxicity and clinical response, blood and tumor samples will be obtained to assess immunologic measures relevant to galectin biology and pembrolizumab T-cell checkpoint inhibition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GR-MD-02 + pembrolizumab | Experimental | Drug: GR-MD-02, Drug: Pembrolizumab4 mg/kg GR-MD-02 in combination with standard pembrolizumab treatment. |
| Pembrolizumab Monotherapy | Placebo comparator | Drug: Placebo, Drug: Pembrolizumab4 mg/kg placebo in combination with standard pembrolizumab treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with unresectable or metastatic melanoma including unknown primary, mucosal or uveal melanomas. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression during or after platinum-containing chemotherapy are eligible. PD-L1 testing is not needed for OHN cancers.
- Patients who have received anti-PD1 or anti-PD-L1 in the past are eligible if it has been at least 6 months since the last anti-PD-1 or PD-L1 dose, they meet all other eligibility criteria and progression of malignancy has been documented on imaging. Progression for this patient subset is defined as the appearance of one or more new metastatic sites, or a 5% or greater increase in the sum of diameter of target lesions or an unequivocal increase in non-target site. Treatment naïve melanoma patients are eligible.
- Patients must be ≥ 18 years of age.
- ECOG performance status of 0-2.
- Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy.
Key exclusion criteria (20 listed)
- Patients who have previously received a galectin antagonist.
- Patients with active autoimmune disease except for autoimmune thyroiditis or vitiligo (see Appendix C).
- Patients with history of autoimmune colitis.
- Patients with untreated brain metastases. Patients with treated brain metastases who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible.
- Patients requiring other systemic oncologic therapy, including experimental therapies.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GR-MD-02Also: Galactoarabino-rhamnogalactouronatePatients will receive up to seventeen doses of GR-MD-02 intravenously over 85 Days. | Drug | GR-MD-02 + pembrolizumab |
| PlaceboPatients will receive up to seventeen doses of placebo intravenously over 85 Days. | Drug | Pembrolizumab Monotherapy |
| PembrolizumabAlso: KeytrudaPatients will receive 200mg doses of pembrolizumab intravenously over 85 Days. | Drug | GR-MD-02 + pembrolizumab, Pembrolizumab Monotherapy |
Primary outcome
Overall response rate based on disease imaging
Time frame: From date of randomization until the date of first documented progression, assessed up to 63 weeks.
Determine the objective response of GR-MD-02 + pembrolizumab versus pembrolizumab monotherapy in patients with advanced MM or HNSCC
6 secondary outcomes
Evaluation of GAL-3 expression
Time frame: Screening and Day 68
Evaluation of predictive biomarker
Time frame: Day 85
Frequency of Immune-mediated adverse events
Time frame: From time of informed consent to week 63
Evaluation of antiviral immunity
Time frame: Day 85
Evaluation of antiviral immunity
Time frame: Day 85
Evaluation of antiviral immunity
Time frame: Day 85
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brendan D. Curti, MD principal investigator
Providence Health & Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GR-MD-02 and Pembrolizumab in people with Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma, run by Providence Health & Services at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate based on disease imaging (time frame: From date of randomization until the date of first documented progression, assessed up to 63 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2023.