NCT03152565

Brief 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..

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2018

Typical duration for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 11, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 15, 2017

Completed
10 months until next milestone

Study Start

First participant enrolled

March 12, 2018

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2019

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 5, 2020

Completed
Last Updated

October 6, 2020

Status Verified

October 1, 2020

Enrollment Period

1.3 years

First QC Date

May 11, 2017

Last Update Submit

October 5, 2020

Conditions

Colorectal Carcinoma

Outcome Measures

Primary Outcomes (2)

  • Dose of Avelumab in combination with Autologous Dendritic Cells

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

    18 months

  • Progression Free Survival

    Percentage of patients without progression of disease

    6 months

Secondary Outcomes (3)

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

    18 months

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

    18 months

  • Immunophenotype signature in tumor biopsies before and during treatment.

    18 months

Study Arms (1)

Avelumab in combination ADC vaccine

EXPERIMENTAL

Patients 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.

Drug: Avelumab

Interventions

AvelumabDRUG

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.

Also known as: Autologous Dendritic Cells
Avelumab in combination ADC vaccine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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).
  • b) 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.

You may not qualify if:

  • 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.
  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Hospital Clínic Barcelona

Barcelona, 08024, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08024, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46009, Spain

Location

Instituto Valenciano de Oncología

Valencia, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Related Publications (1)

  • 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.

    PMID: 36083313DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

avelumab

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Study Officials

  • Joan Maurel Santasusana, M.D.

    Hospital Clinic of Barcelona

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 11, 2017

First Posted

May 15, 2017

Study Start

March 12, 2018

Primary Completion

June 30, 2019

Study Completion

October 5, 2020

Last Updated

October 6, 2020

Record last verified: 2020-10

Data Sharing

IPD Sharing
Will not share

Locations

ES(8)