Trial Search Results
A Pilot Study to Evaluate the Safety and Efficacy of Combination Checkpoint Blockade Plus External Beam Radiotherapy in Subjects With Stage IV Melanoma
This is an open-label, multicenter pilot Phase 1 study of the checkpoint antibodies ipilimumab and nivolumab in combination with radiotherapy (RT) in 18 subjects with unresectable stage IV melanoma. All subjects will receive concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses, followed by nivolumab monotherapy (240 mg) every 2 weeks. Radiotherapy will be initiated after the first dose and before the second dose of immunotherapy.
Stanford is currently accepting patients for this trial.
Ludwig Institute for Cancer Research
Collaborator: Bristol-Myers Squibb
- Drug: Ipilimumab
- Drug: Nivolumab
- Radiation: Radiotherapy
1. Histologic diagnosis of stage IV metastatic melanoma, with 1 melanoma lesion that can
be safely irradiated in the opinion of the radiation oncologist (note: subjects with
primary ocular and mucosal melanoma are permitted). Lesions may include, but are not
- Symptomatic lymphadenopathy
- Bothersome cutaneous disease
- Hepatic metastases
- Pulmonary metastases
2. Excluding the lesion intended to undergo radiation, subjects must have at least 1
unresectable, non-bony lesion that is measurable radio-graphically (based on RECIST
3. Any number of prior therapies (including none). For subjects who have received prior
systemic treatment with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),
Programmed death 1 (PD-1) and/or Programmed death-ligand 1 (PD-L1) therapy, the last
monoclonal antibody administration should be no less than 6 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.
4. Subjects must have completed chemotherapy, targeted therapy, investigational therapy,
other immunotherapy, prior radiotherapy, or major surgery (requiring general
anesthesia) at least 28 days before administration of the first dose of study drug(s).
Subjects undergoing minor surgical procedures and biopsies that do not require general
anesthesia may begin receiving study therapy if sufficiently recovered as determined
by the treating investigator. Clinically significant toxicity experienced during any
prior therapy must be resolved or stabilized before the first dose of study drug(s).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Life expectancy ≥ 4 months.
7. 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
- Total bilirubin ≤ 1.5 × (< 3 mg/dL for subjects with Gilbert's disease)
- Serum creatinine ≤ 1.5 x Upper Limit of Normal or creatinine clearance ≥ 40
mL/min (if using the Cockcroft-Gault formula below):
Female Creatinine Clearance = [(140 - age in years) x weight in kg x 0.85] / [72 x
serum creatinine in mg/dL] Male Creatinine Clearance = [(140 - age in years) x weight
in kg x 1.00] / [72 x serum creatinine in mg/dL]
8. Age ≥ 18 years.
9. Able and willing to give valid written informed consent.
1. Any contraindications for ipilimumab (Yervoy®) or nivolumab (Opdivo®) as per the
2. Unresolved immune-related adverse events following prior biological therapy. Subjects
with asymptomatic endocrinopathy may enroll.
3. 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 are permitted in
the absence of active autoimmune disease.
4. History of motor neuropathy considered to be of autoimmune origin (e.g.,
Guillain-Barre Syndrome, Myasthenia Gravis).
5. Other active, concurrent malignancy that requires ongoing systemic treatment or
interferes with radiographic assessment of melanoma response as determined by the
6. Active brain metastases or leptomeningeal metastases. Subjects with brain metastases
are eligible if metastases have been treated and there is no magnetic resonance
imaging (MRI) evidence of progression for 4 weeks or more after treatment is complete
and within 28 days prior to the first dose of nivolumab administration. There must
also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10
mg/day prednisone equivalents) for at least 2 weeks prior to study drug
7. Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to
Hepatitis B or C without evidence of active infection may be allowed.
8. History of severe allergic reactions to any unknown allergens or any components of the
9. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
10. Requirement of radiotherapy to treat brain metastases or receipt of any non-study
systemic therapy for cancer or any other experimental/investigational treatment.
11. Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.
12. Lack of availability for immunological and clinical assessments or post-study
follow-up contact to determine relapse and survival.
13. Women who are breastfeeding or who are pregnant as evidenced by a positive serum
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) 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 HCG) within 24 hours of the first dose of
14. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use 2 methods of effective contraception.
15. Any condition that, in the clinical judgment of the treating physician, is likely to
prevent the subject from complying with any aspect of the protocol or that may put the
subject at unacceptable risk.
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study