- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01608594
Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-α2b for Melanoma
Neoadjuvant Combination Biotherapy With Ipilimumab (3 mg/kg or 10 mg/kg) and High Dose IFN-Α2B in Patients With Locally/Regionally Advanced/Recurrent Melanoma: a Randomized Safety, Efficacy and Biomarker Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Hillman Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men and women, at least 18 years of age
- ECOG performance status 0 or 1
- Histologic diagnosis of melanoma staged:
- Tx or T1-4 and
- N1b, or N2b, or N2c, or N3
- M 0 that may present as any of the following groups:
- Primary melanoma with clinically apparent regional lymph node metastases, biopsy confirmed
- Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin, biopsy confirmed
- Clinically or histologically detected primary melanoma involving multiple regional nodal groups, biopsy confirmed
- Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, biopsy confirmed
- Patients with intransit or satellite metastases with or without lymph node involvement are allowed if considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist.
NOTE: All patients must be determined to be surgically resectable at baseline to be eligible for this neoadjuvant study.
- Patients must undergo biopsy (punch) or open biopsy (if done as part of a clinically indicated baseline diagnostic procedure) within 14 days of entry into the study. Lymphadenectomy/definitive surgery will be performed after at least 2 and generally not longer than 4 weeks of induction HDI-ipilimumab therapy. Additional delays for definitive lymphadenectomy/surgery are allowed if clinically indicated while awaiting the resolution of potential adverse events from HDI-ipilimumab therapy.
- Patients must have been evaluated by standard-of-care full body imaging studies (CT, PET-CT or MRI) as part of the initial clinical work-up at baseline (no more than 4 weeks prior to study enrollment) and after completion of induction HDI-ipilimumab (at 6-8 weeks after the first dose of ipilimumab/HDI and prior to the definitive lymphadenectomy procedure).
- Required values for initial laboratory tests:
- WBC ≥ 3000/uL
- ANC ≥ 1500/uL
- Platelets ≥ 100 x 103/uL
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 1.8 mg/dL
- AST/ALT ≤ 2.5 x ULN
- Bilirubin ≤ 1.5 ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- No active or chronic infection with HIV, Hepatitis B, or Hepatitis C
Exclusion Criteria:
- Clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
- Evidence of soft tissue involvement by gross extranodal extension of tumor manifest by fixation to the fascia, or matting of nodal tissue that would compromise surgical resection as determined by the surgical oncologist.
- History of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
- Autoimmune disease exclusions: a history of inflammatory bowel disease, a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator/Sub-Investigator will make the administration of ipilimumab or HDI hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
- Underlying heart conditions if deemed ineligible for surgery by cardiology consult.
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
- Prior treatment with ipilimumab or CD137 agonist or CTLA-4 inhibitor or agonist.
- Prior radiotherapy, chemotherapy, including infusion or perfusion therapy for current disease or any immunotherapy including tumor vaccines, interferon-alfa, interleukins, levamisole or other biologic response modifiers within the past 4 weeks.
- Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks. A history of occasional use of steroid inhalers is allowed.
- Women of childbearing potential (who:
- Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
- Have a positive pregnancy test at baseline, or
- Are pregnant or breastfeeding.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ipilimumab 10 mg/kg + HDI
Ipilimumab 10 mg/kg + standard dose IFN alpha
|
Ipilimumab IV infusion:
Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.
Other Names:
|
Experimental: Ipilimumab 3mg/kg + HDI
Ipilimumab 3mg/kg + standard dose IFN alpha
|
Ipilimumab IV infusion:
Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events
Time Frame: 5 years
|
To estimate the safety profile of investigational combination biotherapy with standard HDI and ipilimumab at 10 mg/kg and 3 mg/kg
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic response rate
Time Frame: 1 year
|
To monitor the pathologic tumor response rate (complete response, microscopic residual disease and macroscopic residual disease) at the time of definitive surgery
|
1 year
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Radiologic preoperative response rate
Time Frame: 1 year
|
The response rate will be estimated by the percentage of patients who achieve CR, PR or SD by RECIST criteria, with corresponding exact 90% confidence limits being reported for each dose level.
|
1 year
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Progression Free Survival
Time Frame: 5 years
|
To determine length of time during and after treatment during which the disease does not get worse.
Both arms are to be compared.
|
5 years
|
Overall Survival
Time Frame: 5 years
|
the percentage of subjects alive five years after diagnosis or treatment.
|
5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Diwakar Davar, MD, University of Pittsburgh
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- 11-063 (Other Identifier: University of Pittsburgh Cancer Institute)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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