Recurrent MelanomaPhase 2NCT00003895

Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma

A Phase 2 study testing HPV 16 E7:12-20, gp100:209-217(210M) and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IA Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This randomized pilot phase II trial studies how well vaccine therapy works in treating human leukocyte antigen class 1 histocompatibility, A-2 (HLA-A2) positive patients with melanoma. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Read more about this study

Who is it for?: Ages 17 years and older
Conditions the study is for: Recurrent Melanoma, Stage IA Melanoma, Stage IB Melanoma
What is being tested?: HPV 16 E7:12-20, gp100:209-217(210M) and laboratory biomarker analysis
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteUnited States
Study dates: Apr 1999to Sep 2013
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 17 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision
Patients whose melanoma is > 4.0 mm thick who have positive or negative regional lymph nodes are also eligible
After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible
Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques
Patients must be ambulatory with good performance status (Karnofsky performance status [PS] 80-100)
White blood cell (WBC) >= 3500/mm^3

Show all 14Show fewer

Platelets (Plt) >= 100,000/mm^3
Hemoglobin >= 9 gm/100 ml
Serum creatinine =< 2 mg/dl
Total bilirubin =< 2.0 mg/dl
Patients must have recovered from any effects of major surgery and be free of significant systemic infection
Patients must be negative for human immunodeficiency virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) (or negative by Western blot if ELISA is positive) if they are considered to be at high risk; others do not require serologic testing if there are no symptoms or risk factors for HIV disease
Women of childbearing potential must have a negative pregnancy test and should avoid becoming pregnant while on treatment
Patients must give written informed consent prior to initiation of therapy; patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy

Who cannot join

Patients must not have clinically detectable distant metastases
Patients who require or are likely to require systemic corticosteroids for intercurrent illness
Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy
Patient should be free of any other cancers or deemed at low risk for their recurrence

Trial locations and contacts

1 site in 1 country.

United States1 site

Providence Portland Medical Center
Portland, Oregon, 97213

Other trials in United States

About this study

Official title: A Randomized Phase II Trial to Determine the Immune Response to a Mutated gp100 Melanoma Peptide (209-2M) Vaccine in HLA-A2 Positive Patients With a >1mm Melanoma on Initial Biopsy

Read the detailed description

PRIMARY OBJECTIVES:

To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick.

II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.

III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.

IV. To determine whether analysis of antigen-specific T-cells using specific HLA-A2/peptide tetramers is an effective method for monitoring the immune response of patients undergoing peptide vaccination and to compare it to enzyme-linked immunosorbent spot (ELISPOT), limiting dilution analysis (LDA) and measurement of intracellular cytokine production (fastimmune).

To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide.

VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant subcutaneously (SC) every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive gp100:209-217(210M) peptide vaccine and HPV16E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

In both arms, patients undergo sentinel lymph node biopsy approximately 10 days after the second vaccination. Patients with positive lymph nodes undergo complete lymph node dissection and resume vaccinations.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Conditions: Recurrent Melanoma, Stage IA Melanoma, Stage IB Melanoma, Stage IIA Melanoma, Stage IIB Melanoma, Stage IIC Melanoma
Being tested: HPV 16 E7:12-20, gp100:209-217(210M), laboratory biomarker analysis
Medical subject headings: Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HPV 16 E7:12-20Biological
Given SC
gp100:209-217(210M)Biological
Also called G9 209-2M
Given SC
laboratory biomarker analysisOther
Correlative studies

Study groups in NCT00003895
Study group	Role	What they receive
gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks)	Experimental	Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis. Receives: Biological: HPV 16 E7:12-20; Biological: gp100:209-217(210M); Other: laboratory biomarker analysis
gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)	Experimental	Patients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis. Receives: Biological: HPV 16 E7:12-20; Biological: gp100:209-217(210M); Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide
Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods.
Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses.
Measured: Baseline to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 1999Sep 2013

First posted18 Jul 2003 (estimated)
Study startApr 1999
Primary completionSep 2013
Study completionSep 2013

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 Recurrent MelanomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00003895
Sponsor's protocol ID: NCI-2013-02096
Other IDs: NCI-2013-02096, CDR0000067065, NCI-T98-0081, PPMC-IRB-99-9, 99-9, T98-0081, R21CA082614
Status last verified: Dec 2016
First submitted: 1 Nov 1999
Last updated: 20 Feb 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Not yet recruitingPhase 2
A Study Comparing Cemiplimab-based Treatments for Adult Participants With Locally Advanced Basal Cell Skin Cancer (laBCC)
Locally Advanced Basal Cell Carcinoma
RecruitingPhase 1
A Phase 1 Study to Evaluate OPB-201 in Recurrent Endometrial and Platinum-resistant Ovarian Cancer.
Endometrial Cancer Recurrent, Endometrial Cancer
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

All Recurrent Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Phase II Trial to Determine the Immune Response to a Mutated gp100 Melanoma Peptide (209-2M) Vaccine in HLA-A2 Positive Patients With a >1mm Melanoma on Initial Biopsy
ClinicalTrials.gov ID: NCT00003895
Acronym / sponsor ID: NCI-2013-02096
Conditions: Recurrent Melanoma, Stage IA Melanoma, Stage IB Melanoma, Stage IIA Melanoma, Stage IIB Melanoma, Stage IIC Melanoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: Apr 1999
Primary completion: Sep 2013 (actual)
Study completion: Sep 2013 (actual)
First posted: 18 Jul 2003 (estimated)
Results: Posted 20 Feb 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

To define the toxicity of administration of gp100: 209-217 (210M) (gp100:209-217[210M] peptide vaccine) and the human papillomavirus (HPV) 16 E7(12-20) peptide (HPV16E7:12-20 peptide vaccine), with adjuvant Montanide ISA-51 (incomplete Freund's adjuvant), to patients who present with a primary melanoma > 1 mm thick.

II. To measure the T-cell response to the modified self-gp100: 209-217 (210M) peptide and the unmodified parental glycoprotein 100 (gp100) peptide.

III. To measure the T-cell response to the control human leukocyte antigen (HLA)-A2.1 restricted cytotoxic T-lymphocyte (CTL) epitope of papilloma virus HPV16E7:12-20.

To determine whether there is a difference between the induction of primary peptide-specific T-cell immune responses to the self gp100 peptide versus the foreign E7 peptide.

VI. To compare the immune response induced by vaccinating every 2 weeks for 6 months (a total of 13 vaccinations) vs. every 3 weeks for 6 months (a total of 9 vaccinations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then yearly thereafter.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks)	Experimental	Biological: HPV 16 E7:12-20, Biological: gp100:209-217(210M), Other: laboratory biomarker analysisPatients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 2 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.
gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)	Experimental	Biological: HPV 16 E7:12-20, Biological: gp100:209-217(210M), Other: laboratory biomarker analysisPatients receive gp100:209-217(210M) peptide vaccine and HPV 16 E7:12-20 peptide vaccine mixed with incomplete Freund's adjuvant SC every 3 weeks for 6 months. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo laboratory biomarker analysis.

Who may qualify

Ages: 17 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (14 listed)

Patients must have histologically confirmed primary melanoma of Breslow thickness 1.0-4.0 mm; patients who have had only their initial biopsy are preferred; however, those who have already undergone a wide local excision are also eligible; patients may be enrolled up to three months after their wide local excision
Patients whose melanoma is > 4.0 mm thick who have positive or negative regional lymph nodes are also eligible
After accrual to the original 26 patient goal, all patients must be enrolled prior to sentinel lymph node dissection; patients with previous lymph node dissection will not be eligible
Patients must be HLA typed and be shown to be HLA-A2.1+ by either serologic techniques, flow cytometry, or molecular techniques
Patients must be ambulatory with good performance status (Karnofsky performance status [PS] 80-100)

Key exclusion criteria (4 listed)

Patients must not have clinically detectable distant metastases
Patients who require or are likely to require systemic corticosteroids for intercurrent illness
Patients with any significant medical disease other than the malignancy (e.g. chronic obstructive pulmonary disorder [COPD], patients with ascites or pleural effusions) which in the opinion of the investigator would significantly increase the risk of immunotherapy
Patient should be free of any other cancers or deemed at low risk for their recurrence

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
HPV 16 E7:12-20Given SC	Biological	gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks), gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)
gp100:209-217(210M)Also: G9 209-2MGiven SC	Biological	gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks), gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)
laboratory biomarker analysisCorrelative studies	Other	gp100:209-217(210M) + HPV 16 E7:12-20 (every 2 weeks), gp100:209-217(210M) + HPV 16 E7:12-20 (every 3 weeks)

Primary outcome

T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide
Time frame: Baseline to 6 months
Frequency measures obtained from each assay will be transformed to (common) logs for purposes of analysis. Repeated measures analyses will be performed on longitudinal data to assess patients' immune response profiles over time. Comparability of assay methods will be assessed with correlation analyses, regression analyses, standard parametric and nonparametric tests, and agreement methods. Pre- and post-immunization T-cell immunity to g209-2M peptide, to HPV16E7 peptide, and to a negative control HLA-A2 HIV peptide (pol) were assessed using HLA-A2/peptide tetramer-specific binding analysis. Within-subject analyses were performed to determine differences between pre- and postimmunization responses to the g209 -2M and HPV peptides and to the negative control HIV peptide after completion of 6 months of vaccination. Pre- versus postimmunization response differences were used as criterion measures in between-group (among subjects) analyses.

Results and safety

Results posted to the registry on 20 Feb 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
gp100:209-217(210M)and HPV 16 E7:12-20 (Every 2 Weeks)	18	11
gp100:209-217(210M) and HPV 16 E7:12-20 (Every 3 Weeks)	18	14

Primary outcome: T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide

Time frame: Baseline to 6 months. Mean (90% Confidence Interval). Unit: % of CD8+ T cells

Measure	Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) n = 14	Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20) n = 15
pre-treatment %gp100 g209-2M-specific T cells	0.02 (0.01 to 0.03)	0.01 (0.00 to 0.02)
Post-treatment % gp100 g209-2M-specific T cells	0.97 (0.37 to 1.57)	0.98 (0.04 to 1.92)
Pre-Treatment % HPV16:E7 12-20-specific T cells	0.61 (0 to 1.27)	0.1 (0.04 to 0.16)
Post-Treatment % HPV16:E7 12-20-specific T cells	0.68 (0.31 to 1.05)	1.34 (0.85 to 1.82)

Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20): p <.001, t-test, 2 sided
Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20): p <.0001, t-test, 2 sided
Arm A (Every 2 Weeks, gp100:209-217(210M) and HPV 16 E7:12-20) vs Arm B (Every 3 Weeks, gp100:209-217(210M) + HPV 16 E7:12-20): p = 0.59, t-test, 2 sided

Population analysed: Patients were randomly assigned to two different vaccination schedules: group A received vaccinations every 2 weeks for 6 months (13 total injections), and group B received vaccinations every 3 weeks for 6 months (nine total vaccinations).

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm A (Every 2 Weeks)	1 of 18 (5.6%)	18 of 18 (100%)	Not reported
Arm B (Every 3 Weeks)	0 of 18 (0%)	17 of 18 (94.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Recurrent Melanoma

RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Not yet recruitingPhase 2
A Study Comparing Cemiplimab-based Treatments for Adult Participants With Locally Advanced Basal Cell Skin Cancer (laBCC)
Locally Advanced Basal Cell Carcinoma
RecruitingPhase 1
A Phase 1 Study to Evaluate OPB-201 in Recurrent Endometrial and Platinum-resistant Ovarian Cancer.
Endometrial Cancer Recurrent, Endometrial Cancer
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

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.

Walter J. Urba, MD, PhD principal investigator

Providence Cancer Center, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 14 inclusion and 4 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 20 Feb 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 20 Feb 2017). 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?

T Cell Immunity to gp100 Peptide and to E7 12-20 Papilloma Virus Peptide (time frame: Baseline to 6 months). 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 NCT00003895.

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 20 Feb 2017.