MelanomaPhase 2NCT00610857
Safety and Efficacy of Combination HDI and Anti-CTLA4 for Recurrent Inoperable Stage III or Stage IV Melanoma
A Phase 2 study testing Anti-CTLA4 monoclonal antibody and HDI in people with Melanoma, run by Ahmad Tarhini at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Anti-CTLA4 monoclonal antibody and HDI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPCI Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
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
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- Anti-CTLA4 monoclonal antibody and HDI
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CTLA4 monoclonal antibody and HDIDrug
Also called Anti-CTLA4 monoclonal antibody (CP-675,206)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Anti-CTLA4 monoclonal antibody and HDI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 44 months
Secondary outcomes (3)
Progression-free Survival (PFS)
Time from initial treatment date of to date of documented progression of disease progression (TTP)
Measured: Up to 44 months
1-year Overall Survival (OS)
1-year survival is the estimated probability of surviving one year expressed as a percent (probability of survival is not probability of dying).
Measured: Time from initial treatment date, up to 1 year
Median Overall Survival (Point Estimate)
Median overall survival is the (point) estimate of the time corresponding to 50% estimated probability of survival.
Measured: Up to 44 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2008 (estimated)
- Study startNov 2006
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ahmad Tarhini
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, Ahmad Tarhini, University of Pittsburgh
- Investigators
- Ahmad Tarhini, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00610857
- Sponsor's protocol ID
- 05-125
- Status last verified
- Jun 2017
- First submitted
- 28 Jan 2008
- Last updated
- 22 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00610857
- Acronym / sponsor ID
- 05-125
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Ahmad TarhiniUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Nov 2006
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 8 Feb 2008 (estimated)
- Results
- Posted 17 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-CTLA4 monoclonal antibody and HDI | Experimental | Drug: Anti-CTLA4 monoclonal antibody and HDISpecific 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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):
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-CTLA4 monoclonal antibody and HDIAlso: Anti-CTLA4 monoclonal antibody (CP-675,206)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. | Drug | Anti-CTLA4 monoclonal antibody and HDI |
Primary outcome
Best Objective Response Rate (BORR)
Time frame: Up to 44 months
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
3 secondary outcomes
Progression-free Survival (PFS)
Time frame: Up to 44 months
1-year Overall Survival (OS)
Time frame: Time from initial treatment date, up to 1 year
Median Overall Survival (Point Estimate)
Time frame: Up to 44 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmad Tarhini, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anti-CTLA4 monoclonal antibody and HDI in people with Melanoma, run by Ahmad Tarhini at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Objective Response Rate (BORR) (time frame: Up to 44 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2017.