Unresectable MelanomaPhase 1NCT02115243
Trial of Neoadjuvant Ipilimumab Followed by Melphalan Via Isolated Limb Infusion for Patients With Unresectable In-transit Extremity Melanoma
A Phase 1 study testing Ipilimumab in people with Unresectable Melanoma, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to determine safety profile, initial response rates and progression free survival for the combination therapy of neoadjuvant system ipilimumab followed by ILI with melphalan in patients with in transit melanoma. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Unresectable Melanoma
- What is being tested?
- Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to 7 Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have histologically proven primary or recurrent extremity melanoma, stage IIIB, IIIC, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug)
- Patients with Stage IV disease must have had all distant disease resected at least 30 days prior to regional treatment.
- Patient must be greater than 18 years of age.
- Patient must have an ECOG/Zubrod status of 0-1.
- Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the RECIST criteria. For subjects with a single lesion, archived tissue must be available for research analysis. The sum of target lesion diameters should be at least 10 mm.
- Disease to be treated by ILI must be distal to the planned site of tourniquet placement (which for the leg is generally the apex of the femoral triangle, or for the arm is distal to the deltoid insertion). If provider feels ILI appropriate with disease in these areas, patient may be enrolled with PI approval.
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- Patient must have adequate bone marrow, liver and renal function as assessed by the following:
- Hemoglobin greater than 9.0 g/dl
- White blood count (WBC) of greater than 2000 m3
- Absolute neutrophil count (ANC) greater than 1,000/mm3
- Platelet count greater than 75,000/mm3
- Total bilirubin less than 2.0 x ULN
- ALT and AST less than 2.5 x the ULN
- Creatinine less than 2.0 x ULN
- Patient must have a palpable femoral/radial pulse in the affected extremity.
- Patients must have a life expectancy of greater than 6 months.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
- Amenorrhea greater than 12 consecutive months without another cause, or
- For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level greater than 35 mIU/mL.
- Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
- WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
- Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
- Patient must provide a signed and dated written informed consent prior to registration and any study-related procedures.
- Patient must provide written authorization to allow the use and disclosure of their protected health information at any institution subject to US HIPAA regulations.
- Ability to read and understand English and the ability to complete paper +/- electronic survey assessments.
Who cannot join
- Cardiac disease: Congestive heart failure greater than class II NYHA. Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- Autoimmune disease: History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.]
- Prior allogeneic stem cell transplantation.
- Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- History of or current immunodeficiency disease [e.g. splenectomy or splenic irradiation].
- Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance; any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
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- Concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, adrenal insufficiencies, or if administered at doses of prednisone greater than or equal to 7.5mg daily or equivalent.
- Women of childbearing potential (WOCBP), defined above in Section 5.1, who:
- are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
- have a positive pregnancy test at baseline, or
- are pregnant or breastfeeding.
- Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped.
- Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study.
- Known brain metastasis.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection greater than CTCAE Grade 2.
- Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event greater than CTCAE Grade 2 within 4 weeks of study entry.
- Any other hemorrhage/bleeding event greater than CTCAE Grade 3 within 4 weeks of study entry.
- Evidence or history of bleeding diathesis or coagulopathy.
- Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration.
- Current treatment, or treatment in the previous 24 months, for another non-melanoma malignancy, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix.
- Unable to return at the regular required intervals for reassessment, or study drug administration.
- Patients with known heparin induced thrombocytopenia.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27707
About this study
Official title: A Phase I Trial of Neoadjuvant Ipilimumab Followed by Melphalan Via Isolated Limb Infusion for Patients With Unresectable In-transit Extremity Melanoma
The purpose of this study is to determine safety profile, initial response rates and progression free survival for the combination therapy of neoadjuvant system ipilimumab followed by ILI with melphalan in patients with in transit melanoma.
Hypothesis:
The combination of regional LPAm plus systemic ipilimumab will lead to a larger response rate than either therapy alone.
The combination of regional LPAm plus systemic ipilimumab will cause larger changes in immune cell populations than are seen with either therapy along.
Changes in immune cell populations will predict progression free survival.
- Conditions
- Unresectable Melanoma
- Being tested
- Ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
| Study group | Role | What they receive |
|---|---|---|
| Ipi/ILI | Other | Patients will receive ipilimumab followed by ILI. Receives: Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
The primary objective is to characterize the safety and tolerability of combining IPI and ILI by determining the MTD of IPI when used prior to ILI with LPAM.
Measured: 2 years
Secondary outcomes (2)
Response Rate
Estimate the complete response rate to ipi plus ILI in the patients who received the MTD of ipi.
Measured: 3 years
Progression Free Survival
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study startMay 2014
- Primary completion7 Dec 2015
- Study completion7 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable MelanomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Douglas Tyler, MD, Principal investigator, Duke UniversityApril K Salama, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115243
- Sponsor's protocol ID
- Pro00046479
- Status last verified
- Oct 2018
- First submitted
- 12 Apr 2014
- Last updated
- 29 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Neoadjuvant Ipilimumab Followed by Melphalan Via Isolated Limb Infusion for Patients With Unresectable In-transit Extremity Melanoma
- ClinicalTrials.gov ID
- NCT02115243
- Acronym / sponsor ID
- Pro00046479
- Conditions
- Unresectable Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- 7 Dec 2015 (actual)
- Study completion
- 7 Dec 2015 (actual)
- First posted
- 15 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine safety profile, initial response rates and progression free survival for the combination therapy of neoadjuvant system ipilimumab followed by ILI with melphalan in patients with in transit melanoma.
Hypothesis:
The combination of regional LPAm plus systemic ipilimumab will lead to a larger response rate than either therapy alone.
The combination of regional LPAm plus systemic ipilimumab will cause larger changes in immune cell populations than are seen with either therapy along.
Changes in immune cell populations will predict progression free survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipi/ILI | Other | Drug: IpilimumabPatients will receive ipilimumab followed by ILI. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patient must have histologically proven primary or recurrent extremity melanoma, stage IIIB, IIIC, or stage IV (AJCC staging must be documented in patient's medical record, as determined by CT of the chest, abdomen and pelvis, and/or whole body PET scan, and MRI of the brain within 4 weeks prior to administration of study drug)
- Patients with Stage IV disease must have had all distant disease resected at least 30 days prior to regional treatment.
- Patient must be greater than 18 years of age.
- Patient must have an ECOG/Zubrod status of 0-1.
- Patient's disease must be bi-dimensionally measurable by caliper or radiological method as defined in the RECIST criteria. For subjects with a single lesion, archived tissue must be available for research analysis. The sum of target lesion diameters should be at least 10 mm.
Key exclusion criteria (24 listed)
- Cardiac disease: Congestive heart failure greater than class II NYHA. Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
- Autoimmune disease: History of or current active autoimmune diseases, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.]
- Prior allogeneic stem cell transplantation.
- Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- History of or current immunodeficiency disease [e.g. splenectomy or splenic irradiation].
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 |
|---|---|---|
| Ipilimumab | Drug | Ipi/ILI |
Primary outcome
Safety and tolerability
Time frame: 2 years
The primary objective is to characterize the safety and tolerability of combining IPI and ILI by determining the MTD of IPI when used prior to ILI with LPAM.
2 secondary outcomes
Response Rate
Time frame: 3 years
Progression Free Survival
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2018.
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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.
Douglas Tyler, MD principal investigator
Duke University
April K Salama, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab in people with Unresectable Melanoma, run by Duke University 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 25 inclusion and 24 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 29 Oct 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety and tolerability (time frame: 2 years). 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 29 Oct 2018.