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Colorectal CarcinomaPhase 1/2AVEVACNCT03152565

Avelumab Plus Autologous Dendritic Cell Vaccine in Pre-treated Metastatic Colorectal Cancer Patients

A Phase 1/2 study testing Avelumab in people with Colorectal Carcinoma, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 8 sites in Spain.

Completed

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

Official record
Search all trials

Trial summary

Single arm Phase I/II multicentric open labeled, with translational sub-study, of avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients.. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Carcinoma
What is being tested?
Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
8 sitesSpain
Study dates
12 Mar 2018to 5 Oct 2020
Phase
Phase 1/2
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

  • Written informed consent of approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
  • Histological diagnosis of MSS colorectal adenocarcinoma.
  • Metastatic disease treated with at least two chemotherapy line, with or without targeted therapies.
  • Male or female subjects aged ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria.
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  • Lactate dehydrogenase (LDH) levels (<1.5 ULN) (between 250-450 U/L). Maximum allowed 675 U/L.
  • Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normality (ULN) and Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
  • Negative serum pregnancy test at screening for women of childbearing potential.
  • Highly effective contraception for both male and female subjects throughout the study and for at least 60 days after last avelumab treatment administration if the risk of conception exists.
  • Adequate hematological function: a) Haemoglobin ≥ 9 g/dL (may have been transfused).
  • Platelet count ≥ 100 × 109/L. c) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
  • Renal: Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
  • Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

Who cannot join

  • Subjects with brain metastases.
  • Prior organ transplantation, including allogeneic stem-cell transplantation.
  • Presence of clinical ascites.
  • Modified Charlson score >2 (excluded cancer).
  • Significant acute or chronic infections including, among others: Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Positive test for Hepatitis C Virus (HCV) surface antigen and / or confirmatory Hepatitis C Virus (HCV) Ribonucleic acid (RNA) (if anti-HCV antibody tested positive).
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a)Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible. b) Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg/24 h of prednisone or equivalent. c) Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intraocular, or inhalation) are acceptable.
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  • Local positive serologic determination to: Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (Anti-HBc), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), HCV ribonucleic acid test (HCV RNA), HIV-I RNA, Agp24 III-V + Carbonic anhydrase III-V (CAIII-V) ½ (MLIA) serum, Immunoglobulin G (Ig) antigen core HBV, reaginic antibodies (RPR) for Systemic Erythematosus Lupus (SEL-RPR) serum, immunoglobulin G (IgG), cytomegalovirus (EIA), Anti-Human T-Cell Lymphotropic I/II Viruses (HTLV) Antigens (if patient came from endemic zone), Anti-Trypanosoma Cruzi antibodies, Chagas (if patient came from endemic zone), when RPR positive or doubtful for confirmation: IgG Treponema pallidum (ELISA), Immunoglobulin M (IgM) Treponema pallidum (ELISA), when IgG T. Pallidum doubtful: Pt confirmatory IgG/IgM, Treponema pallidum (LIA).
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 according National Cancer Institute-Common Terminology for Common Adverse Events/NCI-CTCAE v 4.03), - any history of anaphylaxis, or uncontrolled asthma. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable.
  • Pregnancy or lactation.
  • Known alcohol or drug abuse.
  • All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment
  • Any psychiatric condition that would impede the understanding of informed consent
  • Vaccination other study treatment is prohibited, within 4 weeks of the first dose of avelumab and while on trial.
  • History of other tumors in the past 5 years.
  • Active infections.
  • Current immunosuppressive treatment, except for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."
  • Known hypersensitivity to avelumab, ADC vaccines or their components.
  • Legal incapacity or limited legal capacity.
  • Patients with pneumonitis and pulmonary fibrosis.
  • Patients with cardiac medical history: Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of ADC + avelumab combination therapy.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Spain8 sites

  • Hospital Clínic Barcelona

    Barcelona, 08024

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08024

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Puerta de Hierro

    Madrid

  • Hospital Universitario y Politécnico La Fe

    Valencia, 46009

  • Instituto Valenciano de Oncología

    Valencia

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

Other trials in Spain

About this study

Official title: A Single Arm Phase I-II Multicenter Trial With Avelumab Plus Autologous Dendritic Cell Vaccine to Determine Safety and Preliminary Efficacy of the Combination in Pre-treated Mismatch Repair-proficient (MSS) Metastatic Colorectal Cancer Patients.

Single arm Phase I/II multicentric open labeled, with translational sub-study, of avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients..

Read the detailed description

This 2-phases study will first evaluate two different doses/schema of avelumab plus autologous dendritic cell vaccine (ADC) vaccines, in intention to define which dose is effective without hampering safety. Second phase will consist in an standard analysis of efficacy and progression free survival. It is expected that 4 Spanish Sites will include patients in phase I and 8 Spanish Centers will include patients in the phase II of the study

Being tested
Avelumab
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • AvelumabDrug

    Also called Autologous Dendritic Cells

    Autologous Dendritic Cells vaccine: A dose of ADC at days 1, 14, 28, 42 and 56 (total of 5 doses), and thereafter every 6 months until disease progression (maximum of 6 additional doses) or unacceptable toxicity.

    Avelumab will be administered intravenously at a dose of 10 mg per kilogram of body weight, every 14 days until disease progression or unacceptable toxicity.

Study groups in NCT03152565
Study groupRoleWhat they receive
Avelumab in combination ADC vaccineExperimentalPatients in both phases will receive Avelumab biweekly intravenous during a maximum of 12 months and biweekly 10x106 ADC vaccine (intradermal) for five doses (days 1, 14, 28, 42 and 56) followed by a maximum of 6 doses every 6 months.
Receives: Drug: Avelumab

What is being measured

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

  1. Dose of Avelumab in combination with Autologous Dendritic Cells

    Dose of avelumab at which no dose limiting toxicity is shown.

    Measured: 18 months

  2. Progression Free Survival

    Percentage of patients without progression of disease

    Measured: 6 months

Secondary outcomes (3)

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Frequency, nature and number of patients developing adverse events throughout follow up

    Measured: 18 months

  2. Modified Consensus Molecular Subtypes' (CMS) classification of Immunophenotype signature in tumor biopsies before and during treatment.

    Modified CMS classification by NanoString

    Measured: 18 months

  3. Immunophenotype signature in tumor biopsies before and during treatment.

    MSS, RAS and BRAF mutation status at baseline and during treatment.

    Measured: 18 months

Timeline

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

  1. First posted15 May 2017
  2. Study start12 Mar 2018
  3. Primary completion30 Jun 2019
  4. Study completion5 Oct 2020

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03152565
Sponsor's protocol ID
GEMCAD-1602
Other IDs
2016-003838-24, 2016
Acronym
AVEVAC
Status last verified
Oct 2020
First submitted
11 May 2017
Last updated
6 Oct 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Espanol-Rego M, Fernandez-Martos C, Elez E, Foguet C, Pedrosa L, Rodriguez N, Ruiz-Casado A, Pineda E, Cid J, Cabezon R, Oliveres H, Lozano M, Gines A, Garcia-Criado A, Ayuso JR, Pages M, Cuatrecasas M, Torres F, Thomson T, Cascante M, Benitez-Ribas D, Maurel J. A Phase I-II multicenter trial with Avelumab plus autologous dendritic cell vaccine in pre-treated mismatch repair-proficient (MSS) metastatic colorectal cancer patients; GEMCAD 1602 study. Cancer Immunol Immunother. 2023 Apr;72(4):827-840. doi: 10.1007/s00262-022-03283-5. Epub 2022 Sep 9.

    PubMed 36083313

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Avelumab in people with Colorectal Carcinoma, run by Grupo Espanol Multidisciplinario del Cancer Digestivo at 8 sites in Spain.

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 21 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 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Spain. 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 combined 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.

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?

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?

Dose of Avelumab in combination with Autologous Dendritic Cells (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT03152565, which also lists 1 linked publication.

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 6 Oct 2020.

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