Melanoma Stage IIIPhase 2NCT04007588
A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma
A Phase 2 study testing Nivolumab, BMS-986205 and Ipilimumab in people with Melanoma Stage III and Melanoma Stage IV, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV
- What is being tested?
- Nivolumab, BMS-986205 and Ipilimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Sep 2019to 19 Dec 2019
- 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
- Histologic or cytologic diagnosis of resectable stage III or IV cutaneous melanoma. Patients with melanoma of mucosal origin are not eligible. Patients with acral melanoma that fit criteria are eligible. Patients must have clinically detectable stage III (clinically detectable N1b, N1c, N2b, N2c, N3b or N3c) or stage IV resectable 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 ≥2,000/mcL
- absolute neutrophil count ≥1,500/mcL
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- platelets ≥100,000/mcL
- hemoglobin ≥9.0g/dL
- 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 ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- C-Reactive Protein < institutional ULN
- Quantitative or qualitative G6PD assay results must not suggest underlying G6PD deficiency
- Measurable disease (by CT, PET/CT or MRI)
- Prior therapies including targeted therapy and immunotherapy are not allowed, with the exception of adjuvant Ipilimumab or Interferon-α-2b.
- Ability to understand and the willingness to sign a written informed consent document.
- Ability to swallow pills intact and without GI issues which may impact medication absorption.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (Refer to Appendix B) for the duration of treatment with study treatment(s) plus 5 months post-treatment completion (i.e. 30 days plus the time required for nivolumab to undergo approximately 5 half-lives).
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment(s) plus 7 months post-treatment completion (i.e. 90 days plus the time required for nivolumab to undergo approximately 5 half-lives). In addition, male participants must be willing to refrain from sperm donation during this time. This criterion applies to azoospermic males as well.
Who cannot join
- A history of prior treatment with PD-1 inhibitor, CTLA-4 inhibitor or IDO inhibition. Prior therapy with ipilimumab or Interferon-α-2b in the adjuvant setting is permitted. Participants may not have received live/attenuated vaccines within 30 days of first treatment.
- Participants with uveal or mucosal melanoma
- Participants with known brain metastases must have documented stability for at least 30 days directly prior to study enrollment 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 nivolumab, ipilimumab, methylene blue or BMS-986205. History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
- Need for systemic steroids at the time of enrollment. Physiologic replacements at a dose of less than 10 mg daily prednisone equivalent is allowed.
- Blood Methemoglobin > ULN, assessed in an arterial or venous blood sample or by co-oximetry
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- Participants with active ILD/pneumonitis or history of ILD/ pneumonitis requiring steroids.
- 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.
- 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 nivolumab or BMS-986205, breastfeeding should be discontinued if the mother is treated with nivolumab or BMS-986205. 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. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Participant with a personal or family (ie, in a first-degree relative) history of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that put them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to randomization.
- Participant with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD levels prior to randomization.
- Participants must not have a history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg. hormone replacement after adrenal crisis).
- Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization.
- History of other malignancy within 3 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS of > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
- Participants who have had major surgery requiring general anesthesia or significant trauma who have not recovered per physician determination for at least 14 days prior to randomization.
- Participants with conditions known to interfere significantly with the absorption of oral medication, as per investigator judgment.
- Participants with uncontrolled adrenal insufficiency.
- Prior history of serotonin syndrome.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has approved OPDIVO® (nivolumab), YERVOY® (ipilimumab), and a combination of the two as treatment options for metastatic melanoma.
The FDA (the U.S. Food and Drug Administration) has not approved the combination of nivolumab and BMS-986205 as a treatment for any disease. This research study is looking for more information on the efficacy the combination of nivolumab and BMS-986205 in the treatment of melanoma.
Nivolumab, Ipilimumab, and BMS-986205 are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab, Ipilimumab, and BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer.
In this research study, the investigators are going to look at the following while the participants are receiving the study drug(s):
- The effectiveness (how well the drug works), safety, and tolerability of Nivolumab, BMS-986205 and Nivolumab, and Ipilimumab and Nivolumab in people with resectable stage III or IV melanoma
- Conditions
- Melanoma Stage III, Melanoma Stage IV
- Being tested
- Nivolumab, BMS-986205, Ipilimumab
- Keywords
- Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
Nivolumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer
BMS-986205Drug
BMS-986205 is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer
IpilimumabDrug
Also called YERVOY
Ipilimumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Ipilimumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab+BMS-986205 | Experimental | * Nivolumab will be administered intravenously Day 1 of each 28 day cycle.
* BMS-986205 will be administered orally on a daily basis Receives: Drug: Nivolumab; Drug: BMS-986205 |
| Nivolumab | Experimental | -Nivolumab will be administered intravenously Day 1 of each 28 day cycle. Receives: Drug: Nivolumab |
| Nivolumab+Ipilimumab | Experimental | * Nivolumab will be administered intravenously Day 1 of each 28 day cycle.
* Ipilimumab will be administered intravenously every 6 weeks Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathologic Response Rate
Complete Pathological response rate or near pathological complete response rate on each treatment arm
Measured: 2 years
Secondary outcomes (4)
Recurrence free survival
Time from treatment start to recurrence of melanoma
Measured: 2 years
Overall Survival Rate
Time from treatment start to death
Measured: 2 years
Changes In Infiltrating immune cells From Pre-Treatment To Time Of Excision
Changes in immune cells in the tumor micro environment including CD8 T-cells
Measured: 2 Years
Rates of adverse events and serious adverse events on the different treatment arms.
Rates of different grade adverse events on each treatment arm
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start6 Sep 2019
- Primary completion19 Dec 2019
- Study completion19 Dec 2019
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Elizabeth Buchbinder, Dana-Farber Cancer Institute
- Investigators
- Elizabeth I Buchbinder, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04007588
- Sponsor's protocol ID
- 19-043
- Status last verified
- Feb 2020
- First submitted
- 1 Jul 2019
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma
- ClinicalTrials.gov ID
- NCT04007588
- Acronym / sponsor ID
- 19-043
- Conditions
- Melanoma Stage III, Melanoma Stage IV
- Keywords
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 6 Sep 2019 (actual)
- Primary completion
- 19 Dec 2019 (actual)
- Study completion
- 19 Dec 2019 (actual)
- First posted
- 5 Jul 2019 (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.
This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has approved OPDIVO® (nivolumab), YERVOY® (ipilimumab), and a combination of the two as treatment options for metastatic melanoma.
The FDA (the U.S. Food and Drug Administration) has not approved the combination of nivolumab and BMS-986205 as a treatment for any disease. This research study is looking for more information on the efficacy the combination of nivolumab and BMS-986205 in the treatment of melanoma.
Nivolumab, Ipilimumab, and BMS-986205 are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab, Ipilimumab, and BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer.
In this research study, the investigators are going to look at the following while the participants are receiving the study drug(s):
- The effectiveness (how well the drug works), safety, and tolerability of Nivolumab, BMS-986205 and Nivolumab, and Ipilimumab and Nivolumab in people with resectable stage III or IV melanoma
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nivolumab+BMS-986205 | Experimental | Drug: Nivolumab, Drug: BMS-986205* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * BMS-986205 will be administered orally on a daily basis |
| Nivolumab | Experimental | Drug: Nivolumab-Nivolumab will be administered intravenously Day 1 of each 28 day cycle. |
| Nivolumab+Ipilimumab | Experimental | Drug: Nivolumab, Drug: Ipilimumab* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * Ipilimumab will be administered intravenously every 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histologic or cytologic diagnosis of resectable stage III or IV cutaneous melanoma. Patients with melanoma of mucosal origin are not eligible. Patients with acral melanoma that fit criteria are eligible. Patients must have clinically detectable stage III (clinically detectable N1b, N1c, N2b, N2c, N3b or N3c) or stage IV resectable melanoma.
- Age ≥ 18 years.
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- Participants must have normal organ and marrow function as defined below:
- Quantitative or qualitative G6PD assay results must not suggest underlying G6PD deficiency
Key exclusion criteria (20 listed)
- A history of prior treatment with PD-1 inhibitor, CTLA-4 inhibitor or IDO inhibition. Prior therapy with ipilimumab or Interferon-α-2b in the adjuvant setting is permitted. Participants may not have received live/attenuated vaccines within 30 days of first treatment.
- Participants with uveal or mucosal melanoma
- Participants with known brain metastases must have documented stability for at least 30 days directly prior to study enrollment 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 nivolumab, ipilimumab, methylene blue or BMS-986205. History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
- Need for systemic steroids at the time of enrollment. Physiologic replacements at a dose of less than 10 mg daily prednisone equivalent is allowed.
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 |
|---|---|---|
| NivolumabAlso: OPDIVONivolumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer | Drug | Nivolumab, Nivolumab+BMS-986205, Nivolumab+Ipilimumab |
| BMS-986205BMS-986205 is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer | Drug | Nivolumab+BMS-986205 |
| IpilimumabAlso: YERVOYIpilimumab is a types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Ipilimumab work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer | Drug | Nivolumab+Ipilimumab |
Primary outcome
Major Pathologic Response Rate
Time frame: 2 years
Complete Pathological response rate or near pathological complete response rate on each treatment arm
4 secondary outcomes
Recurrence free survival
Time frame: 2 years
Overall Survival Rate
Time frame: 2 years
Changes In Infiltrating immune cells From Pre-Treatment To Time Of Excision
Time frame: 2 Years
Rates of adverse events and serious adverse events on the different treatment arms.
Time frame: 2 years
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 5 Feb 2020.
- Individual participant dataSharing planned: Yes. 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
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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.
Elizabeth I Buchbinder, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab, BMS-986205 and Ipilimumab in people with Melanoma Stage III and Melanoma Stage IV, run by Dana-Farber Cancer Institute at 2 sites 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 21 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 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
Major Pathologic Response Rate (time frame: 2 years). 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 5 Feb 2020.