MelanomaPhase 1NCT01608594
Neoadjuvant Combination Therapy With Ipilimumab and HighDose IFN-α2b for Melanoma
A Phase 1 study testing administration of ipilimumab10mg/kg and administration of ipilimumab 3mg/kg + HDI in people with Melanoma, run by Diwakar Davar at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and potential effectiveness of a new treatment for advanced and recurrent melanoma involving the combination of Ipilimumab and IFN-α2b before surgery and to test for biomarker studies in blood and/or tumor to better understand this disease, how best to treat it and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- administration of ipilimumab10mg/kg and administration of ipilimumab 3mg/kg + HDI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 21 May 2013to 27 Feb 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women, at least 18 years of age
- ECOG performance status 0 or 1
- Histologic diagnosis of melanoma staged:
- Tx or T1-4 and
- N1b, or N2b, or N2c, or N3
- M 0 that may present as any of the following groups:
Show all 23Show fewer
- Primary melanoma with clinically apparent regional lymph node metastases, biopsy confirmed
- Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin, biopsy confirmed
- Clinically or histologically detected primary melanoma involving multiple regional nodal groups, biopsy confirmed
- Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, biopsy confirmed
- Patients with intransit or satellite metastases with or without lymph node involvement are allowed if considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist.
- NOTE: All patients must be determined to be surgically resectable at baseline to be eligible for this neoadjuvant study.
- Patients must undergo biopsy (punch) or open biopsy (if done as part of a clinically indicated baseline diagnostic procedure) within 14 days of entry into the study. Lymphadenectomy/definitive surgery will be performed after at least 2 and generally not longer than 4 weeks of induction HDI-ipilimumab therapy. Additional delays for definitive lymphadenectomy/surgery are allowed if clinically indicated while awaiting the resolution of potential adverse events from HDI-ipilimumab therapy.
- Patients must have been evaluated by standard-of-care full body imaging studies (CT, PET-CT or MRI) as part of the initial clinical work-up at baseline (no more than 4 weeks prior to study enrollment) and after completion of induction HDI-ipilimumab (at 6-8 weeks after the first dose of ipilimumab/HDI and prior to the definitive lymphadenectomy procedure).
- Required values for initial laboratory tests:
- WBC ≥ 3000/uL
- ANC ≥ 1500/uL
- Platelets ≥ 100 x 103/uL
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 1.8 mg/dL
- AST/ALT ≤ 2.5 x ULN
- Bilirubin ≤ 1.5 ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- No active or chronic infection with HIV, Hepatitis B, or Hepatitis C
Who cannot join
- Clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
- Evidence of soft tissue involvement by gross extranodal extension of tumor manifest by fixation to the fascia, or matting of nodal tissue that would compromise surgical resection as determined by the surgical oncologist.
- History of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
- Autoimmune disease exclusions: a history of inflammatory bowel disease, a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator/Sub-Investigator will make the administration of ipilimumab or HDI hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
Show all 15Show fewer
- Underlying heart conditions if deemed ineligible for surgery by cardiology consult.
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
- Prior treatment with ipilimumab or CD137 agonist or CTLA-4 inhibitor or agonist.
- Prior radiotherapy, chemotherapy, including infusion or perfusion therapy for current disease or any immunotherapy including tumor vaccines, interferon-alfa, interleukins, levamisole or other biologic response modifiers within the past 4 weeks.
- Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks. A history of occasional use of steroid inhalers is allowed.
- Women of childbearing potential (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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Neoadjuvant Combination Biotherapy With Ipilimumab (3 mg/kg or 10 mg/kg) and High Dose IFN-Α2B in Patients With Locally/Regionally Advanced/Recurrent Melanoma: a Randomized Safety, Efficacy and Biomarker Study
The purpose of this study is to evaluate the safety and potential effectiveness of a new treatment for advanced and recurrent melanoma involving the combination of Ipilimumab and IFN-α2b before surgery and to test for biomarker studies in blood and/or tumor to better understand this disease, how best to treat it and what patients should be treated with this combination.
Read the detailed description
Neoadjuvant therapy allows new insights into melanoma and its biological and immunologic response to therapeutic interventions, such as ipilimumab. Neoadjuvant ipilimumab therapy for high-risk melanoma patients with bulky regional stage IIIB-C lymphadenopathy may result in improved clinical outcome in this group of patients that are more likely to respond to immunotherapeutic interventions and without increased morbidity. Through the design of neoadjuvant trials in which it is possible to obtain biopsy samples, a greater understanding of the dynamic interaction between tumors and the immune system is possible. This should lead to the identification of new targets for the treatment of melanoma and aid in the development of new combinations that may have greater efficacy and acceptable toxicity, to build on the clinical, immunologic, and molecular effect of this therapy for patients with melanoma.
- Conditions
- Melanoma
- Being tested
- administration of ipilimumab10mg/kg, administration of ipilimumab 3mg/kg + HDI
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
administration of ipilimumab10mg/kgDrug
Also called MDX-010, MDX-101, BMS-734016, Yervoy
Ipilimumab IV infusion:
- Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery
- After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart
- Dose continued 12 weeks later for 4 additional doses given 12 weeks apart
Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.
administration of ipilimumab 3mg/kg + HDIDrug
Also called MDX-010, MDX-101, BMS-734016, Yervoy
Ipilimumab IV infusion:
- Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery
- After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart
- Dose continued 12 weeks later for 4 additional doses given 12 weeks apart
Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks.
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab 10 mg/kg + HDI | Experimental | Ipilimumab 10 mg/kg + standard dose IFN alpha Receives: Drug: administration of ipilimumab10mg/kg |
| Ipilimumab 3mg/kg + HDI | Experimental | Ipilimumab 3mg/kg + standard dose IFN alpha Receives: Drug: administration of ipilimumab 3mg/kg + HDI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
To estimate the safety profile of investigational combination biotherapy with standard HDI and ipilimumab at 10 mg/kg and 3 mg/kg
Measured: 5 years
Secondary outcomes (4)
Pathologic response rate
To monitor the pathologic tumor response rate (complete response, microscopic residual disease and macroscopic residual disease) at the time of definitive surgery
Measured: 1 year
Radiologic preoperative response rate
The response rate will be estimated by the percentage of patients who achieve CR, PR or SD by RECIST criteria, with corresponding exact 90% confidence limits being reported for each dose level.
Measured: 1 year
Progression Free Survival
To determine length of time during and after treatment during which the disease does not get worse. Both arms are to be compared.
Measured: 5 years
Overall Survival
the percentage of subjects alive five years after diagnosis or treatment.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study start21 May 2013
- Primary completion14 Feb 2017
- Study completion27 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diwakar Davar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Diwakar Davar, University of Pittsburgh
- Investigators
- Diwakar Davar, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01608594
- Sponsor's protocol ID
- 11-063
- Other IDs
- 11-063
- Status last verified
- Aug 2018
- First submitted
- 26 May 2012
- Last updated
- 28 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.
PubMed 36648215Tarhini A, Lin Y, Lin H, Rahman Z, Vallabhaneni P, Mendiratta P, Pingpank JF, Holtzman MP, Yusko EC, Rytlewski JA, Rao UNM, Ferris RL, Kirkwood JM. Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-alpha2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire. J Immunother Cancer. 2018 Oct 23;6(1):112. doi: 10.1186/s40425-018-0428-5.
PubMed 30352626
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Combination Biotherapy With Ipilimumab (3 mg/kg or 10 mg/kg) and High Dose IFN-Α2B in Patients With Locally/Regionally Advanced/Recurrent Melanoma: a Randomized Safety, Efficacy and Biomarker Study
- ClinicalTrials.gov ID
- NCT01608594
- Acronym / sponsor ID
- 11-063
- Conditions
- Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Diwakar DavarUniversity, hospital or other
- Study start
- 21 May 2013 (actual)
- Primary completion
- 14 Feb 2017 (actual)
- Study completion
- 27 Feb 2017 (actual)
- First posted
- 31 May 2012 (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 evaluate the safety and potential effectiveness of a new treatment for advanced and recurrent melanoma involving the combination of Ipilimumab and IFN-α2b before surgery and to test for biomarker studies in blood and/or tumor to better understand this disease, how best to treat it and what patients should be treated with this combination.
Detailed description
Neoadjuvant therapy allows new insights into melanoma and its biological and immunologic response to therapeutic interventions, such as ipilimumab. Neoadjuvant ipilimumab therapy for high-risk melanoma patients with bulky regional stage IIIB-C lymphadenopathy may result in improved clinical outcome in this group of patients that are more likely to respond to immunotherapeutic interventions and without increased morbidity. Through the design of neoadjuvant trials in which it is possible to obtain biopsy samples, a greater understanding of the dynamic interaction between tumors and the immune system is possible. This should lead to the identification of new targets for the treatment of melanoma and aid in the development of new combinations that may have greater efficacy and acceptable toxicity, to build on the clinical, immunologic, and molecular effect of this therapy for patients with melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab 10 mg/kg + HDI | Experimental | Drug: administration of ipilimumab10mg/kgIpilimumab 10 mg/kg + standard dose IFN alpha |
| Ipilimumab 3mg/kg + HDI | Experimental | Drug: administration of ipilimumab 3mg/kg + HDIIpilimumab 3mg/kg + standard dose IFN alpha |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Men and women, at least 18 years of age
- ECOG performance status 0 or 1
- Histologic diagnosis of melanoma staged:
- Tx or T1-4 and
- N1b, or N2b, or N2c, or N3
Key exclusion criteria (15 listed)
- Clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
- Evidence of soft tissue involvement by gross extranodal extension of tumor manifest by fixation to the fascia, or matting of nodal tissue that would compromise surgical resection as determined by the surgical oncologist.
- History of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
- Autoimmune disease exclusions: a history of inflammatory bowel disease, a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
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 |
|---|---|---|
| administration of ipilimumab10mg/kgAlso: MDX-010, MDX-101, BMS-734016, YervoyIpilimumab IV infusion: * Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery * After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart * Dose continued 12 weeks later for 4 additional doses given 12 weeks apart Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks. | Drug | Ipilimumab 10 mg/kg + HDI |
| administration of ipilimumab 3mg/kg + HDIAlso: MDX-010, MDX-101, BMS-734016, YervoyIpilimumab IV infusion: * Day 0 (within 1-2 weeks of baseline biopsy) every 3 weeks for 2 doses followed by definitive surgery * After surgery recover-y resume at the same dose for 2 additional doses given 3 weeks apart * Dose continued 12 weeks later for 4 additional doses given 12 weeks apart Interferon Alfa-2b will be given concurrently with ipilimumab. Each patient will receive Interferon Alfa-2b at 20 MU/m²/day intravenously for 5 consecutive days out of 7 every week for 4 weeks, followed by 10 MU/m²/d subcutaneously every other day, 3 times each week for 2 weeks, followed by definitive surgery. After surgery recovery, Interferon Alfa-2b will be resumed at 10 MU/m²/d subcutaneously, every other day three times a week for 46 additional weeks. | Drug | Ipilimumab 3mg/kg + HDI |
Primary outcome
Adverse Events
Time frame: 5 years
To estimate the safety profile of investigational combination biotherapy with standard HDI and ipilimumab at 10 mg/kg and 3 mg/kg
4 secondary outcomes
Pathologic response rate
Time frame: 1 year
Radiologic preoperative response rate
Time frame: 1 year
Progression Free Survival
Time frame: 5 years
Overall Survival
Time frame: 5 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 28 Aug 2018.
- Derived from this study: PubMed 36648215Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.
- Derived from this study: PubMed 30352626Tarhini A, Lin Y, Lin H, Rahman Z, Vallabhaneni P, Mendiratta P, Pingpank JF, Holtzman MP, Yusko EC, Rytlewski JA, Rao UNM, Ferris RL, Kirkwood JM. Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-alpha2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire. J Immunother Cancer. 2018 Oct 23;6(1):112. doi: 10.1186/s40425-018-0428-5.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
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.
Diwakar Davar, 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 1 study testing administration of ipilimumab10mg/kg and administration of ipilimumab 3mg/kg + HDI in people with Melanoma, run by Diwakar Davar 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 23 inclusion and 15 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 28 Aug 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?
Adverse Events (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01608594, which also lists 2 linked publications.
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 28 Aug 2018.