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Metastatic Colorectal AdenocarcinomaPhase 1NCT02600949

Personalized Peptide Vaccine in Treating Patients With Advanced Pancreatic Cancer or Colorectal Cancer

A Phase 1 study testing Imiquimod, Pembrolizumab and Sotigalimab in people with Metastatic Colorectal Adenocarcinoma and Metastatic Pancreatic Ductal Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Imiquimod, Pembrolizumab and Sotigalimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
1 siteUnited States
Study dates
11 May 2016to 31 May 2027
Phase
Phase 1

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

  • Metastatic CRC or PDA planned to or have undergone complete surgical resection (metastatectomy) and also for PDA participants with localized disease planned for primary tumor resection.
  • Any lines (including zero) of therapy prior to tissue harvest.
  • Adequate tumor tissue availability
  • Adults (age ≥ 18)
  • ECOG PS 0-1
  • Life expectancy >12 months for Cohort C and >9 months for Cohort D
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  • Adequate organ and marrow function
  • Ability to understand and the willingness to sign a written informed consent document.
  • As the effects of a peptide based vaccine, pembrolizumab or APX005M on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception at study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant, she should inform her treating physician immediately. Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), sexually active participants must use birth control during and for >120 days after the study. Abstinence is also an acceptable form of birth control.
  • For Cohort C only: participants must have metastatic CRC and are planned to or have undergone complete metastecomy/ies and agree to have post-operative blood draw for ctDNA testing within 6 weeks following surgical resection.

Who cannot join

  • History of HIV or AIDS
  • Patients with brain metastasis
  • Serious autoimmune conditions
  • Use of chronic immune suppressive medications.
  • Uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women of child bearing potential who are pregnant or breastfeeding. Women with a positive pregnancy test at enrollment or prior to administration of vaccine. .
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  • Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Known history of active TB (Bacillus Tuberculosis).
  • Hypersensitivity to therapy drugs or their components.
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Active coagulopathy.
  • History of arterial thrombosis within 3 months prior to starting study treatment.
  • History of New York Heart Association Class 3-4 heart failure or myocardial infarction within 6 months prior to starting therapy.
  • Known history of Hepatitis B or known active Hepatitis C.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Pilot Study of the Feasibility and Safety of a Personalized Peptide Vaccine in Patients With Advanced Pancreatic Ductal Adenocarcinoma or Colorectal Adenocarcinoma

This phase I trial studies the side effects and best way to give personalized peptide vaccine in patients with pancreatic or colorectal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Personalized peptide vaccine is a vaccine developed from patient's own tumor cells and blood in order to use as a biological therapy. Biological therapies, such as personalized peptide vaccine may attack tumor cells and stop them from growing or kill them.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Demonstrate that developing a custom vaccine for metastatic pancreatic ductal adenocarcinoma (PDA) and colorectal cancer (CRC) patients is feasible. (cohorts A and B)

II. Show that a custom peptide-based vaccine in combination with imiquiomod, pembrolizumab, and/or sotigalimab (APX005M) is safe. (cohorts A and B and C and D)

SECONDARY OBJECTIVES:

  1. Determine the clinical benefit of the peptide vaccine alone or combined with pembrolizumab or pembrolizumab and APX005M. (cohorts A and B and C and D)

II. Demonstrate the antigenicity of each vaccine. (cohorts A and B and C and D)

III. The change in neoantigen-specific T cell responses at 12 weeks after initiation of personalized peptide vaccination. (cohorts C and D)

IV. Relapse-free survival and circulating tumor deoxyribonucleic acid (ctDNA) clearance rate. (cohorts C and D)

OUTLINE: Patients are assigned to 1 of 3 cohorts.

COHORT A: Patients receive personalized synthetic tumor-associated peptide vaccine therapy subcutaneously (SC) on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.

COHORT B: Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.

COHORTS C AND D: Patients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.

After completion of study treatment, patients are followed for 6 months.

Being tested
Imiquimod, Pembrolizumab, Sotigalimab, Synthetic Tumor-Associated Peptide Vaccine Therapy, Computed Tomography
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • ImiquimodDrug

    Also called Aldara, R 837, S 26308, Zyclara

    Applied topically

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • SotigalimabBiological

    Also called APX 005, APX 005M, APX-005M, APX005M

    Given IV

  • Synthetic Tumor-Associated Peptide Vaccine TherapyBiological

    Given SC

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, CT

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging

    Undergo MRI

Study groups in NCT02600949
Study groupRoleWhat they receive
Cohort A (personalized vaccine, imiquimod)ExperimentalPatients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients then receive imiquimod cream topically in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
Receives: Drug: Imiquimod; Biological: Synthetic Tumor-Associated Peptide Vaccine Therapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging
Cohort B (personalized vaccine, imiquimod, pembrolizumab)ExperimentalPatients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and at weeks 0 and 6, then every 3 months, and at week 39.
Receives: Drug: Imiquimod; Biological: Pembrolizumab; Biological: Synthetic Tumor-Associated Peptide Vaccine Therapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging
Cohort C and D (vaccine, imiquimod, pembrolizumab, APX005M)ExperimentalPatients receive personalized synthetic tumor-associated peptide vaccine therapy SC on day 1 of weeks 0, 1, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Beginning 15 minutes after each vaccine is administered, patients receive imiquimod cream topically. Patients also receive pembrolizumab IV over 30 minutes every 3 weeks until week 24 in the absence of disease progression or unacceptable toxicity. Beginning about 1 hour after each vaccine, patients also receive sotigalimab IV over 60 minutes on day 1 of weeks 0, 1, 3, 4, 6, 12, and 24 in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans at baseline and weeks 6,12, and 24, then every 3 months, and at week 39.
Receives: Drug: Imiquimod; Biological: Pembrolizumab; Biological: Sotigalimab; Biological: Synthetic Tumor-Associated Peptide Vaccine Therapy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

What is being measured

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

  1. Proportion of enrolled patients for whom a personalized vaccine is developed and ready to administer (cohorts A and B)

    Measured: Up to 12 weeks post-enrollment

  2. Proportion of enrolled patients who receive at least 1 dose of vaccine at any time post-enrollment (cohorts A and B)

    Measured: Up to 44 weeks

  3. Incidence of adverse events (AEs)

    Defined as the proportion of subjects who experience at least one toxicity event per National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. A toxicity event is defined as at least one grade 3 or 4 non-hematologic or grade 4 hematologic toxicity. Proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.

    Measured: Up to 24 weeks

Secondary outcomes (12)

  1. Proportion of patients who have received at least one dose of vaccine that is alive and progression free defined based on response criteria according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    Progression free includes complete response (CR), partial response (PR), and stable disease (SD). The target proportion is 45%, and a proportion of 20% or lower will be considered as not having the desired efficacy.

    Measured: At 12 weeks post-vaccination (second re-staging scan)

  2. Progression-free survival (cohorts A and B and C)

    Estimated by the Kaplan-Meier method, along with the 95% confidence intervals, and log-rank test will be used to assess the time to event variable differences under different patient subgroups.

    Measured: The time between the date of first vaccination and evidence of progression on computed tomography scan or the date of death due to any cause, assessed up to 6 months after the last dose of vaccine

  3. Response rate (cohort A and B)

    Response rate includes both CR and PR and will be evaluated using a Simon optimal two-stage design.

    Measured: Up to 12 weeks

  4. Change in tumor biomarker (CA19-9, carcinoembryonic antigen [CEA] or circulating free deoxyribonucleic acid [cfDNA] mutation)

    Measured: Up to 6 months

  5. Overall survival

    Estimated by the Kaplan-Meier method, along with the 95% confidence intervals, and log-rank test will be used to assess the time to event variable differences under different patient subgroups.

    Measured: The time from first vaccination to death, assessed up to 6 months after the last dose of vaccine

  6. Recurrence-free survival (cohort C and D)

    Estimated by the Kaplan-Meier method.

    Measured: Up to 6 months

  7. Rate of circulating deoxyribonucleic acid (ctDNA) clearance (cohort C and D)

    A linear mixed model will also be fitted to correlate ctDNA clearance and neoantigen-specific CD8+ T cell over time.

    Measured: Up to 6 months

  8. Change in neoantigen-specific T cell response (cohort C and D)

    The difference in log2 transformed T cell response from baseline to 12 weeks will be calculated for each peptide and patient. This endpoint will focus upon the log2-fold change at 12 weeks for the max peptide (i.e., the peptide with the greatest change). Descriptive statistics, including mean, standard deviation, median and range, will be used to summarize the changes. A paired t-test will be used to evaluate the changes from baseline to 12 weeks post initiation of vaccination.

    Measured: Baseline to 12 weeks after initiation of personalized peptide vaccination

  9. Correlation of T-cell activation against vaccinated peptides and ctDNA dynamics (cohort C and D)

    Measured: Up to 6 months

  10. Tumor microenvironment immune infiltration and progression biopsies (cohort C and D)

    Measured: Baseline, up to 6 months

  11. T cell IFN-gamma release in response to selected personalized peptide antigens

    Measured: Up to 6 months

  12. Levels of intracellular cytokine staining of T cells

    Assessed by flow cytometry in response to stimulation with personalized peptide antigens.

    Measured: Up to 6 months

Timeline

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

  1. First posted9 Nov 2015 (estimated)
  2. Study start11 May 2016
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
119 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02600949
Sponsor's protocol ID
2014-1029
Other IDs
NCI-2016-00015, 2014-1029
Status last verified
Oct 2026
First submitted
6 Nov 2015
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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