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

Sponsor:	University of Pittsburgh
Information provided by (Responsible Party):	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00610857

Purpose

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.

Condition	Intervention	Phase
Melanoma	Drug: Anti-CTLA4 monoclonal antibody and HDI	Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label
Official Title:	Safety and Efficacy of Combination Biotherapy With High-dose Interferon Alfa-2b and Anti-CTLA4 Monoclonal Antibody for Recurrent Inoperable Stage III or Stage IV Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

Drug Information available for: Immunoglobulins Cytotoxic T-lymphocyte antigen 4 Globulin, Immune

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

Test the hypothesis that the combination of HDI and anti-CTLA-4 monoclonal antibody will improve the response rate in patients with recurrent inoperable AJCC stage III and stage IV melanoma. [ Time Frame: 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Test the hypothesis that the combination therapy will improve the overall survival rate and the progression for these patients. [ Time Frame: 1 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	37
Study Start Date:	November 2006
Estimated Study Completion Date:	December 2012
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Anti-CTLA4 monoclonal antibody and HDI 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 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. Other Name: Anti-CTLA4 monoclonal antibody (CP-675,206)

Arms

Assigned Interventions

Experimental: Anti-CTLA4 monoclonal antibody and HDI

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

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.

Other Name: Anti-CTLA4 monoclonal antibody (CP-675,206)

Detailed Description:

Immunity to melanoma appears to be central to disease control in the adjuvant and advanced disease settings. Spontaneous regression has been reported in melanoma, suggesting a role for host immunity, indirectly supported by the presence of lymphoid infiltrates at primary melanoma associated with tumor regression.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
Patients must not have previous therapy with Anti-CTLA4 monoclonal antibodies (including CP-675,206 and MDX-010). Previous therapy with Interferon-alfa 2b in the adjuvant or metastatic setting is allowed. Previous therapy with other biological agents (including vaccines and GM-CSF) is allowed.
Patients must have ECOG performance status of 0 or 1.
Patients must not have autoimmune disorders (except vitiligo). Patients with positive titers for autoimmune antibodies are allowed on the study in the absence of history of clinical manifestations of autoimmune disease.
Patients must not have conditions of immunosuppression or chronic requirement for treatment with systemic steroids, including oral steroids, continuous use of topical steroid creams or ointments, or any inhaled steroid containing inhalers. Patients who discontinue use of these classes of medication for at least 2 weeks are eligible. Treatment with steroids or other immunosuppressant medications is allowed during the study if clinically required to treat side effects related to autoimmunity that may develop secondary to the study agents.
Patients must be free of brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs. If known to have prior brain metastases, must not have evidence of active brain disease on two successive MRI evaluations at least 3 months apart (one of which is £ 4 weeks prior to starting the study drugs).
Female patients of child bearing potential must have a negative pregnancy test, and must not be breast feeding.
Patients must agree to use effective contraception (both males and females).

Exclusion Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00610857

Locations

United States, Pennsylvania
UPCI Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

University of Pittsburgh

Investigators

Principal Investigator:

Ahmad Tarhini, MD

University of Pittsburgh

More Information

No publications provided

Responsible Party:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00610857 History of Changes
Other Study ID Numbers:	05-125
Study First Received:	January 28, 2008
Last Updated:	January 6, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cytotoxic T-lymphocyte antigen 4
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 09, 2012