Safety and Efficacy of Combination HDI and Anti-CTLA4 for Recurrent Inoperable Stage III or Stage IV Melanoma

NCT00610857 | Completed Phase 2 Results DMC

• 1 other identifier: 05-125
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the safety and efficacy of the combination of HDI and anti-CTLA-4 monoclonal antibody for patients with recurrent inoperable stage III or stage IV melanoma.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Best Objective Response Rate (BORR)

  Intention to treat response rate is estimated by the proportion of patients with a best response of CR, PR, or SD by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.0

  Up to 44 months

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Up to 44 months

• 1-year Overall Survival (OS)

  Time from initial treatment date, up to 1 year

• Median Overall Survival (Point Estimate)

  Up to 44 months

Study Arms (1)

Anti-CTLA4 monoclonal antibody and HDI

EXPERIMENTAL

Specific Aim #1: Test the hypothesis that the combination of IFNa-2b and anti-CTLA-4 monoclonal antibody will improve the response rate in patients with recurrent inoperable AJCC stage III and stage IV melanoma. Our therapeutic target is achieving, with acceptable toxicity, a 20% or better rate of objective response, CR or PR by RECIST criteria, as compared to the 5% to 10% expected in patients eligible for study. Study size is planned in terms of our primary efficacy endpoint, objective response.

Drug: Anti-CTLA4 monoclonal antibody and HDI

Interventions

Anti-CTLA4 monoclonal antibody and HDI DRUG

One course of therapy consists of three cycles (1 cycle=28days). Anti-CTLA4 monoclonal antibody (15 mg/kg i.v.) will be given during the first cycle only. HDI will be given all three cycles - cycle 1: 20 MU/m2 i.v. on days 0, 1, 2, 3, 4 a week (MTWRF) for 4 weeks; cycle 2: 10 MU/m2 s.c. 3 days a week (MWF) for 4 weeks; and cycle 3: 10 MU/m2 s.c. 3 days a week (MWF) for 4 weeks. Response assessment will be carried out at day 56 and day 84. Every patient will receive 3 cycles regardless of response status after the first 2 cycles. However, a patient may be taken off therapy in the event of clinical progression at the discretion of the treating physician. Patients without evidence for disease progression after 3 cycles may be offered additional cycles two weeks after completion of the third cycle. Therapy will continue for a maximum of 12 months.

Also known as: Anti-CTLA4 monoclonal antibody (CP-675,206)

Anti-CTLA4 monoclonal antibody and HDI

Eligibility Criteria

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

You may qualify if:

• Patients must have a written informed consent obtained prior to the initiation of study procedures.
• Male and female subjects greater than or equal to 18 years of age.
• Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 6th edition classification). Cutaneous melanoma, ocular or mucosal melanoma will be eligible.
• Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline measurements must be obtained within 4 weeks prior to initiating therapy.
• Patients must have adequate hematologic, renal, and liver function as evidenced by the following (within 4 weeks prior to starting the study drugs):
• WBC greater than or equal to 3,000/mm3
• Lymphocytes greater than or equal to 1,000/mm3
• Platelets greater than or equal to 100,000/mm3
• Serum Creatinine less than or equal to 1.5 x upper limit of normal (ULN)
• Serum Bilirubin less than or equal to 1.5 x ULN
• Serum AST/ALT less than or equal to 2.5 x ULN
• Serum LDH less than or equal to 2.0 x ULN
• APTT less than \< 40 s
• Patients must have fully recovered from any effects of major surgery, and be free of significant detectable infection.
• Patients must not have received any chemotherapy, hormonal therapy, radiotherapy, or biological therapy within the preceding 4 weeks.

You may not qualify if:

• Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders.
• Treatment with mitomycin C or nitrosureas within six weeks prior to study entry.
• Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial.
• Active infection or antibiotics within one-week prior to study, including unexplained fever (temp \> 38.1°C).
• Treatment with anticoagulants, except to keep an indwelling line patent.
• Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
• Treatment with any investigational product within 28 days of registration.
• History of inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin, or any history of diverticulitis (even a single episode) or evidence of diverticulitis at baseline, including evidence limited to CT-scan only.
• Patients who did not tolerate high-dose interferon-α therapy in the adjuvant setting will be excluded.

Sponsors & Collaborators

• Ahmad Tarhini: lead
• Pfizer: collaborator

Study Sites (1)

UPCI Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

tremelimumab

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

Results Point of Contact

• Title: Ahmad Tarhini, MD
• Organization: University of Pittsburgh Cancer Institute

tarhiniaa@upmc.edu

4126486507

Study Officials

• Ahmad Tarhini, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: January 28, 2008
• First Posted: February 8, 2008
• Study Start: November 1, 2006
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: June 22, 2017
• Results First Posted: October 17, 2016

Record last verified: 2017-06

Locations

US (1)