MelanomaPhase 1NCT02659540
Pilot Study of the Safety/Efficacy of Combination Checkpoint Blockade + External Beam Radiotherapy in Stage IV Melanoma
A Phase 1 study testing Nivolumab, Ipilimumab and Radiotherapy in people with Melanoma, run by Ludwig Institute for Cancer Research at 2 sites in United States.
Trial summary
This is an ongoing, Phase 1, open-label, multicenter, pilot study of the checkpoint antibodies ipilimumab and nivolumab in combination with radiotherapy (RT) in 18 subjects with unresectable Stage IV melanoma. The primary study objective is to evaluate the safety of study treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab, Ipilimumab and Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Oct 2016to 27 Jul 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 diagnosis of Stage IV metastatic melanoma, with 1 melanoma lesion that could be safely irradiated and, in the opinion of the radiation oncologist, was of benefit to the subject to irradiate (note: subjects with primary ocular and mucosal melanoma were permitted). Lesions may have included, but were not limited to:
- Symptomatic lymphadenopathy;
- Bothersome cutaneous disease;
- Hepatic metastases;
- Pulmonary metastases.
- Excluding the lesion intended to undergo radiation, subjects must have had at least 1 unresectable, non-bony lesion that was measurable radiographically (based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
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- Any number of prior therapies (including none). For subjects who had received prior systemic treatment with cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and/or programmed cell death ligand-1 (PD-L1) therapy, the last monoclonal antibody administration should have been no less than 4 weeks prior to start of this protocol therapy and all prior side effects must have resolved to grade 1 or less by the time of the start of this protocol therapy.
- Subjects must have:
- Completed investigational therapy, other immunotherapy, or prior RT at least 28 days before administration of the first dose of study drug(s)
- Completed chemotherapy or targeted therapy at least 14 days before administration of the first dose of study drug(s)
- Sufficiently recovered from prior surgery as determined by the treating Investigator.
- Clinically significant toxicity or pharmacodynamic effects experienced during any prior therapy must have been resolved or stabilized before the first dose of study drug(s).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Life expectancy ≥ 4 months.
- Screening laboratory parameters:
- White blood cell count ≥ 2000/μL;
- Absolute neutrophil count ≥ 1500/μL;
- Platelets ≥ 100,000/μL;
- Hemoglobin ≥ 9 g/dL;
- Aspartate aminotransferase and alanine aminotransferase ≤ 3 × upper limit of normal (ULN);
- Total bilirubin ≤ 1.5 × ULN (< 3 mg/dL for subjects with Gilbert's disease);
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
- Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL];
- Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL].
- Age ≥ 18 years.
- Able and willing to give valid written informed consent.
Who cannot join
- Unresolved immune-related AEs following prior biological therapy. Subjects with asymptomatic endocrinopathy may have enrolled.
- Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents were permitted in the absence of active autoimmune disease.
- History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).
- Other active, concurrent malignancy that required ongoing systemic treatment or interfered with radiographic assessment of melanoma response as determined by the Investigator.
- Active brain metastases or leptomeningeal metastases. Subjects with brain metastases were eligible if metastases had been treated and there was no magnetic resonance imaging (MRI) evidence of progression for 4 weeks or more after treatment was completed and within 28 days prior to the first dose of nivolumab administration. There must also have been no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- Known immunodeficiency or human immunodeficiency virus, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may have been allowed.
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- History of severe allergic reactions to any unknown allergens or any components of the study drugs.
- Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
- Requirement of RT to treat brain metastases or receipt of any non-study systemic therapy for cancer or any other experimental/investigational treatment.
- Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
- Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival.
- Women who were breastfeeding or who were pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) performed within 14 days of the first dose of study drug and by a urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours of the first dose of study drug(s).
- Females of childbearing potential who were sexually active with a nonsterilized male partner must have used 2 methods of effective contraception from screening, and must have agreed to continue using such precautions for 23 weeks after the final dose of investigational product; cessation of birth control after this point should have been discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method were not acceptable methods of birth control.
- [Females of childbearing potential were defined as those who were not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).] Nonsterilized males who were sexually active with a female partner of childbearing potential must have used 2 acceptable methods of effective contraception from Day 1 and for 31 weeks after receipt of the final dose of investigational product.
- Any condition that, in the clinical judgment of the treating physician, was likely to interfere with the interpretability of the data or prevent the subject from complying with any aspect of the protocol or that may have put the subject at unacceptable risk.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Stanford Cancer Institute
Stanford, California, 94304
About this study
Official title: A Pilot (Phase 1) Study to Evaluate the Safety and Efficacy of Combination Checkpoint Blockade (Ipilimumab and Nivolumab) Plus External Beam Radiotherapy in Subjects With Stage IV Melanoma
This is an ongoing, Phase 1, open-label, multicenter, pilot study of the checkpoint antibodies ipilimumab and nivolumab in combination with radiotherapy (RT) in 18 subjects with unresectable Stage IV melanoma. The primary study objective is to evaluate the safety of study treatment. Secondary objectives are to evaluate objective response rate (ORR) and disease control rate (DCR) at Weeks 12 and 18, duration of response, progression-free survival (PFS), and overall survival (OS).
Read the detailed description
All subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy, with RT dosing administered to a target lesion as follows:
- Cohort A: conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each;
- Cohort B: hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each.
Eligible subjects were initially enrolled into Cohort A. After 9 evaluable subjects completed at least the first 2 cycles of concurrent ipilimumab and nivolumab treatment, a safety review was performed and determined that the safety of Cohort A was acceptable based on a protocol-specified tolerability threshold of ≤ 7 of 9 subjects experiencing Grade 3 or 4 drug- or radiation-related adverse events (AEs), where Grade 3 or 4 amylase or lipase abnormalities that were not associated with clinical symptoms were not included in the safety assessment. Additional subjects were then accrued to Cohort B.
Subjects were followed on study for 100 days after the last study drug administration. Post-study follow-up, which occurs at least every 12 (± 1) weeks for 3 years after completion of the 100-day on-study follow-up, is still being performed for some patients .
- Conditions
- Melanoma
- Being tested
- Nivolumab, Ipilimumab, Radiotherapy
- Keywords
- Ipilimumab, Nivolumab, Radiotherapy
- 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 was administered as an intravenous (IV) infusion over approximately 30 or 90 minutes, with dosing calculated using body weight.
IpilimumabDrug
Also called Yervoy
Ipilimumab was administered as an IV infusion over approximately 30 or 90 minutes, with dosing calculated using body weight. The ipilimumab infusion was initiated approximately 30 minutes after the end of the nivolumab infusion on applicable dosing days.
RadiotherapyRadiation
RT was delivered in accordance with cohort assignment and institutional practices.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (Conventional RT) | Experimental | Subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy and was administered to a target lesion at a conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each. Receives: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiotherapy |
| Cohort B (Hypofractionated RT) | Experimental | Subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy and was administered to a target lesion at a hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each. Receives: Drug: Nivolumab; Drug: Ipilimumab; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 100 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment.
Measured: Up to 25 months
Secondary outcomes (7)
Number of Subjects With Tumor Response at Week 12 by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at Weeks 12, 18, and 24, and every 12 weeks (± 7 days) thereafter until progression or start of alternate anticancer therapy. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria (Eisenhauer et al. Eur J Cancer 2009;45:228-47).
Measured: 12 weeks
Number of Subjects With Tumor Response at Week 18 by RECIST 1.1
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at Weeks 12, 18, and 24, and every 12 weeks (± 7 days) thereafter until progression or start of alternate anticancer therapy. Per RECIST 1.1, target lesions are categorized as follows: CR: Disappearance of all target lesions; PR: ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; SD: small changes that do not meet above criteria (Eisenhauer et al. Eur J Cancer 2009;45:228-47).
Measured: 18 weeks
Number of Subjects With Tumor Response at Week 12 by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at Weeks 12, 18, and 24, and every 12 weeks (± 7 days) thereafter until progression or start of alternate anticancer therapy. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria (Bohnsack et al. Ann Oncol 2014;25: iv361-iv72).
Measured: 12 weeks
Number of Subjects With Tumor Response at Week 18 by irRECIST
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at Weeks 12, 18, and 24, and every 12 weeks (± 7 days) thereafter until progression or start of alternate anticancer therapy. Per irRECIST, measurable lesions are categorized as follows: irCR: Complete disappearance of all target lesions; irPR: ≥ 30% decrease from baseline in the TMTB; irPD: ≥ 20% increase from nadir in TMTB; irSD: not meeting above criteria (Bohnsack et al. Ann Oncol 2014;25: iv361-iv72).
Measured: 18 weeks
Duration of Response
Duration of response will be determined for each subject with time origin at the first occurrence of response until the first occurrence of progression or date of death if the subject dies due to any causes before progression. Every effort will be made to follow subjects for progression after they discontinue the study.
Measured: Up to 3 years post-study
Percent of Patients With Progression-free Survival at 3 and 6 Months Post Start of Treatment
Progression-free survival will be defined as the number of days from the date of first dose of study drug to the date of earliest disease progression or to the date of death, if disease progression does not occur. Subjects who do not progress and are still alive will be censored on the date of last follow-up or start of new treatment, whichever comes first. Living patients were censored at last off-study follow-up visit, last scan date, or at the end of study if no follow-up was available. PFS was estimated by Kaplan-Meier methodology.
Measured: At 3 and 6 months after the start of treatment
Percent of Patients With Overall Survival at 12 Months Post Start of Treatment
Overall survival (OS) will be measured for each subject from the date of the first dose of study drug until the recorded date of death or last follow-up. Subjects who are still alive will be censored on the date of last follow-up. Living patients were censored at last off-study follow-up visit, last scan date, or at the end of study if no follow-up was available. OS were estimated by Kaplan-Meier methodology.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2016 (estimated)
- Study start13 Oct 2016
- Primary completion9 May 2019
- Study completion27 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Conquer Cancer Foundation
- Responsible party
- Sponsor
- Investigators
- Michael Postow, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02659540
- Sponsor's protocol ID
- LUD2015-006
- Status last verified
- Oct 2022
- First submitted
- 6 Jan 2016
- Last updated
- 28 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014;25(Supplement 4):iv361-iv72.
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot (Phase 1) Study to Evaluate the Safety and Efficacy of Combination Checkpoint Blockade (Ipilimumab and Nivolumab) Plus External Beam Radiotherapy in Subjects With Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT02659540
- Acronym / sponsor ID
- LUD2015-006
- Conditions
- Melanoma
- Keywords
- Ipilimumab, Nivolumab, Radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Conquer Cancer Foundation
- Study start
- 13 Oct 2016 (actual)
- Primary completion
- 9 May 2019 (actual)
- Study completion
- 27 Jul 2020 (actual)
- First posted
- 20 Jan 2016 (estimated)
- Results
- Posted 2 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an ongoing, Phase 1, open-label, multicenter, pilot study of the checkpoint antibodies ipilimumab and nivolumab in combination with radiotherapy (RT) in 18 subjects with unresectable Stage IV melanoma. The primary study objective is to evaluate the safety of study treatment. Secondary objectives are to evaluate objective response rate (ORR) and disease control rate (DCR) at Weeks 12 and 18, duration of response, progression-free survival (PFS), and overall survival (OS).
Detailed description
All subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy, with RT dosing administered to a target lesion as follows:
- Cohort A: conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each;
- Cohort B: hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each.
Eligible subjects were initially enrolled into Cohort A. After 9 evaluable subjects completed at least the first 2 cycles of concurrent ipilimumab and nivolumab treatment, a safety review was performed and determined that the safety of Cohort A was acceptable based on a protocol-specified tolerability threshold of ≤ 7 of 9 subjects experiencing Grade 3 or 4 drug- or radiation-related adverse events (AEs), where Grade 3 or 4 amylase or lipase abnormalities that were not associated with clinical symptoms were not included in the safety assessment. Additional subjects were then accrued to Cohort B.
Subjects were followed on study for 100 days after the last study drug administration. Post-study follow-up, which occurs at least every 12 (± 1) weeks for 3 years after completion of the 100-day on-study follow-up, is still being performed for some patients .
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A (Conventional RT) | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Radiation: RadiotherapySubjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy and was administered to a target lesion at a conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each. |
| Cohort B (Hypofractionated RT) | Experimental | Drug: Nivolumab, Drug: Ipilimumab, Radiation: RadiotherapySubjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy and was administered to a target lesion at a hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Histologic diagnosis of Stage IV metastatic melanoma, with 1 melanoma lesion that could be safely irradiated and, in the opinion of the radiation oncologist, was of benefit to the subject to irradiate (note: subjects with primary ocular and mucosal melanoma were permitted). Lesions may have included, but were not limited to:
- Excluding the lesion intended to undergo radiation, subjects must have had at least 1 unresectable, non-bony lesion that was measurable radiographically (based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
- Any number of prior therapies (including none). For subjects who had received prior systemic treatment with cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and/or programmed cell death ligand-1 (PD-L1) therapy, the last monoclonal antibody administration should have been no less than 4 weeks prior to start of this protocol therapy and all prior side effects must have resolved to grade 1 or less by the time of the start of this protocol therapy.
- Subjects must have:
- Clinically significant toxicity or pharmacodynamic effects experienced during any prior therapy must have been resolved or stabilized before the first dose of study drug(s).
Key exclusion criteria (15 listed)
- Unresolved immune-related AEs following prior biological therapy. Subjects with asymptomatic endocrinopathy may have enrolled.
- Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents were permitted in the absence of active autoimmune disease.
- History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).
- Other active, concurrent malignancy that required ongoing systemic treatment or interfered with radiographic assessment of melanoma response as determined by the Investigator.
- Active brain metastases or leptomeningeal metastases. Subjects with brain metastases were eligible if metastases had been treated and there was no magnetic resonance imaging (MRI) evidence of progression for 4 weeks or more after treatment was completed and within 28 days prior to the first dose of nivolumab administration. There must also have been no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
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 was administered as an intravenous (IV) infusion over approximately 30 or 90 minutes, with dosing calculated using body weight. | Drug | Cohort A (Conventional RT), Cohort B (Hypofractionated RT) |
| IpilimumabAlso: YervoyIpilimumab was administered as an IV infusion over approximately 30 or 90 minutes, with dosing calculated using body weight. The ipilimumab infusion was initiated approximately 30 minutes after the end of the nivolumab infusion on applicable dosing days. | Drug | Cohort A (Conventional RT), Cohort B (Hypofractionated RT) |
| RadiotherapyRT was delivered in accordance with cohort assignment and institutional practices. | Radiation | Cohort A (Conventional RT), Cohort B (Hypofractionated RT) |
Primary outcome
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 25 months
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 100 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment.
7 secondary outcomes
Number of Subjects With Tumor Response at Week 12 by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: 12 weeks
Number of Subjects With Tumor Response at Week 18 by RECIST 1.1
Time frame: 18 weeks
Number of Subjects With Tumor Response at Week 12 by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time frame: 12 weeks
Number of Subjects With Tumor Response at Week 18 by irRECIST
Time frame: 18 weeks
Duration of Response
Time frame: Up to 3 years post-study
Percent of Patients With Progression-free Survival at 3 and 6 Months Post Start of Treatment
Time frame: At 3 and 6 months after the start of treatment
Percent of Patients With Overall Survival at 12 Months Post Start of Treatment
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- BackgroundBohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014;25(Supplement 4):iv361-iv72.
- Individual participant dataSharing planned: No
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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.
Michael Postow, MD study chair
Memorial Sloan Kettering Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab, Ipilimumab and Radiotherapy in people with Melanoma, run by Ludwig Institute for Cancer Research 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 26 inclusion and 15 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: finished, as of the sponsor's last update on 28 Oct 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 25 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02659540, which also lists 2 linked publications.
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 28 Oct 2022.