Clinical trial NCT01137006: An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
Official title: An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Melanoma
Keywords: Melanoma
Phase I
antibody
melanin
tyrosinase related protein 1
glycoprotein
20D7S
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A dose-escalation study designed to determine the safety, maximum tolerated dose (MTD), anti-melanoma activity, antibody blood levels and progression-free survival (PFS) in participants with malignant melanoma receiving IMC-20D7S either every 2 weeks or every 3 weeks.


Eligibility criteria: Inclusion Criteria:

* Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy \[for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines\] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
* Participant is ≥18 years of age
* Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
* At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
* Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
* Participant has adequate hematological function, hepatic function, and renal function

Exclusion Criteria:

* Participant has undergone major surgery \[e.g., laparotomy, thoracotomy, removal of organ(s)\] within 21 days prior to study entry
* Participant has elective or planned surgery to be conducted during the trial
* Participant has documented and/or symptomatic brain or leptomeningeal metastases
* Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
* Participant has an uncontrolled undercurrent illness
* Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
* Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
* Participant is pregnant or lactating
* Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of IMC-20D7S
timeFrame: Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
measure: Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
timeFrame: Baseline through 30 days post last dose (up to 31 weeks)
Secondary outcomes:
measure: IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: IMC-20D7S PK: Minimal Concentration (Cmin)
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: IMC-20D7S PK: Half-life (t½)
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: IMC-20D7S PK: Clearance (Cl)
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
timeFrame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
measure: Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
timeFrame: Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
measure: Progression-Free Survival (PFS)
timeFrame: First dose to disease progression or death (up to 27 weeks)
measure: Recommend Doses for Phase 2/3 Studies Based on MTD
timeFrame: Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]
Other outcomes:
Locations:
city: Boston
country: United States
facility: ImClone Investigational Site
state: Massachusetts
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
Study officials:
affiliation: Eli Lilly and Company
name: E-mail: ClinicalTrials@ ImClone.com
role: STUDY_DIRECTOR
References: