Phase I Clinical Trial of Tremelimumab Plus MEDI3617 in Patients With Unresectable Stage III or Stage IV Melanoma

NCT02141542 | Completed Phase 1 DMC

• 1 other identifier: 13-613
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, phase I trial, testing the combination of Tremelimumab and MEDI3617 in patients with metastatic melanoma.

Conditions

Metastatic Melanoma

Keywords

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Determination of the maximum tolerated dose (MTD) of the combination of tremelimumab and MEDI3617

  Determination of the maximum tolerated dose (MTD) of the combination of tremelimumab and MEDI3617

  2 Years

Secondary Outcomes (5)

• Overall Survival

  1 Year

• Overall Response Rate

  12 Months

• Disease Control Rate

  2 years

• Time to Tumor Progression

  2 Years

• Duration of Response

  2 Years

Study Arms (1)

Tremelimumab and MEDI3617

EXPERIMENTAL

* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * Tremelimumab-Fixed doses of Tremelimumab are given once per cycle * MEDI3617-MEDI3617 is administered twice per cycle

Drug: Tremelimumab; Drug: MEDI3617

Interventions

Tremelimumab DRUG

Also known as: CP-675,206, Ticilimumab

Tremelimumab and MEDI3617

MEDI3617 DRUG

Also known as: MEDI-3617

Tremelimumab and MEDI3617

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically confirmed melanoma that is metastatic or unresectable;
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease;
• At least 4 weeks since prior treatment (chemotherapy, radiation therapy, hormonal therapy);
• Age ≥18 years;
• Life expectancy of greater than 12 weeks;
• ECOG performance status 0-1
• Participants must have adequate bone marrow, hepatic, and renal function determined within 14 days defined as:
• Platelet count ≥ 100,000/mm3
• Absolute neutrophil count ≥1,000/mm3
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x ULN (upper limit of normal) except subjects with documented Gilbert's syndrome (\>5 x ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN (≤5 x ULN if documented liver metastases are present)
• Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation;
• INR \<1.1 X institutional upper limit of normal

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier;
• Received any prior monoclonal antibody against CTLA-4;
• Any prior ≥ Grade 3 immune-related adverse event (irAE) while receiving immunotherapy or any unresolved irAE at time of study entry
• Participants with a history of hypersensitivity to compounds of similar biologic composition to tremelimumab or any constituent of the product;
• The last dose of prior systemic therapy (e.g. chemotherapy, targeted therapy etc) or radiation therapy (with the exception of palliative radiotherapy) was received less than 14 days prior to the first day of treatment;
• Currently receiving systemic corticosteroids or other immunosuppressive medications or has a medical condition that requires the chronic use of corticosteroids. Note: inhaled and topical steroids are permitted;
• Subjects should not be vaccinated with live attenuated vaccines within one month prior to starting tremelimumab treatment;
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results;
• Active, untreated central nervous system (CNS) metastasis (subjects with brain metastases who are identified at screening may be rescreened after the lesion\[s\] have been appropriately treated and subjects are off corticosteroids);
• Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product, such as conditions associated with frequent diarrhea;
• Active or history of inflammatory bowel disease (eg, colitis, Crohn's), irritable bowel disease, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea. Active or history of systemic lupus erythematosis or Wegener's granulomatosis;
• History of sarcoidosis syndrome;
• Active history of diverticulitis. Note that diverticulosis is permitted;
• History of other malignancy unless the subject has been disease-free for at least 3 years. Non-invasive cancer history (such as carcinoma in situ \[CIS\] that has been resected) is allowed;

Sponsors & Collaborators

• F. Stephen Hodi, MD: lead
• MedImmune LLC: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Ott PA, Nazzaro M, Pfaff KL, Gjini E, Felt KD, Wolff JO, Buchbinder EI, Haq R, Sullivan RJ, Lawrence DP, McDermott DF, Severgnini M, Giobbie-Hurder A, Rodig SJ, Stephen Hodi F. Combining CTLA-4 and angiopoietin-2 blockade in patients with advanced melanoma: a phase I trial. J Immunother Cancer. 2021 Nov;9(11):e003318. doi: 10.1136/jitc-2021-003318.

  PMID: 34772758 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

tremelimumab; MEDI3617

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Patrick Ott, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: May 15, 2014
• First Posted: May 19, 2014
• Study Start: May 1, 2014
• Primary Completion: September 23, 2020
• Study Completion: September 23, 2020
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

US (2)