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Avadomide (CC-122) in Combination With Nivolumab in Advanced Melanoma

Phase 2
Completed
Conditions
Melanoma
Interventions
Drug: CC-122
Drug: Nivolumab
Registration Number
NCT03834623
Lead Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Brief Summary

This study is to find out if the combination of CC-122 (an investigational agent) and Nivolumab will enhance the anti-cancer activity and prevent T-cell exhaustion (T-cells are responsible for maintaining the body's immune response).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
23
Inclusion Criteria
  • Unresectable or metastatic melanoma of cutaneous, mucosal, conjunctival, or unknown origin. Uveal melanoma is not permitted. Cohort 1: Naïve to anti-PD1 therapy Cohort 2: Progressed on previous anti-PD1 therapy. Subjects who have received anti-PD1 therapy in the adjuvant setting for previously resected melanoma are eligible for this cohort provided they have not received any intervening systemic therapy for the relapse
  • Be willing and able to provide written informed consent for the trial.
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Females of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
  • Females of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study 28 days after last dose of avadomide or 5 months after the last dose of nivolumab, whichever is longer. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
  • Males should agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of avadomide or 7 months after last dose of nivolumab, whichever is longer.
  • Adequate organ function
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Exclusion Criteria
  • Has received an investigational drug or other anti-cancer therapy within 3 weeks of the first dose of treatment or < 5 half-lives of that agent, whichever is shorter. Any toxicity from prior therapy must have recovered to < grade 1.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (only exception to this is the need for steroids for CNS metastases; see #6 below). Inhaled, intra-articular, or topical steroids are permissible.
  • Has a history of hypersensitivity to nivolumab.
  • Has a known additional malignancy that is progressing or requires active treatment, the lack of which would pose a risk to the health of the subject, in the opinion of the investigator.
  • Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging for at least four weeks after definitive intervention and using no more than the equivalent of dexamethasone 2mg/d for the management of vasogenic edema, if necessary. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy [</= 10 mg/d equivalent of prednisone] for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with previous grade III/IV toxicity from immunotherapy that led to treatment discontinuation are excluded.
  • Has an active infection requiring systemic therapy.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the investigator.
  • Is pregnant or breastfeeding.
  • Has a known history of Human Immunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C.
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CC-122 Plus NivolumabCC-122Participants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.
CC-122 Plus NivolumabNivolumabParticipants will take CC-122 orally at 2mg daily for 5 consecutive days every 7 days, with intravenous nivolumab (240mg) in days 1 and 15 within a 28-day cycle.
Primary Outcome Measures
NameTimeMethod
Objective Response Rate of CC-122 in Combination With NivolumabUp to 52 weeks

Objective Response Rate of CC-122 in combination with Nivolumab in both anti-PD1 therapy naive advanced melanoma as well as anti-PD1 therapy refractory melanoma (primary refractory or progressing after an initial response or stable disease)

Secondary Outcome Measures
NameTimeMethod
Number of Participants Who Experience Treatment Related Adverse EventsUp to 52 weeks

All Adverse Events and Serious Adverse events will be collected and collated according to grade and frequency. This will include all events considered possibly, probably or definitely related to study therapy.

Tumor ResponseUp to 52 weeks

Tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and and iRECIST (Response Evaluation Criteria in Solid Tumors in immunotherapy) guidelines v1.1. Results will be indicated as number of participants with evaluable tumor response.

Progression Free SurvivalUp to 24 months

Progression free survival will be calculated from the start of study therapy till the first documentation of disease progression, death, or change of treatment. Subjects receiving ongoing therapy at the time of data analysis will be censored

Overall SurvivalUp to 24 months

Overall survival will be calculated from the start of therapy till death from any cause. Subjects alive at the time of data analysis will be censored.

Trial Locations

Locations (1)

H Lee Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

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