ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NIPICOL
Previous Study | Return to List | Next Study

Interest of iRECIST Evaluation for DCR for Evaluation of Patients With Deficient MMR and /or MSI Metastatic Colorectal Cancer Treated With Nivolumab and Ipilimumab (NIPICOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03350126
Recruitment Status : Recruiting
First Posted : November 22, 2017
Last Update Posted : January 23, 2018
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
GERCOR - Multidisciplinary Oncology Cooperative Group

Brief Summary:

This is a non-randomized study, open label phase II study. The purpose of this study is to evaluate disease control rate (DCR) by RECIST and iRECIST at 12 weeks.

Evaluation of RECIST and iRECIST will be done in each center in order to choose the optimal therapy (Assessment by Investigators).

A centralized evaluation of RECIST and iRECIST, will be organized in Saint-Antoine.


Condition or disease Intervention/treatment Phase
Metastatic Cancer Colorectal Drug: Ipilimumab 200 MG in 40 ML Injection Drug: Nivolumab 10 MG/ML Phase 2

Detailed Description:

Recent studies have shown sensitivity to immunotherapy treatment in patients with metastatic colorectal cancer with a dMMR tumor. The association nivolumab plus ipilimumab demonstrated encouraging results with durable responses in these patients.

The criteria for assessing responses for solid tumors are currently based on RECIST 1.1, which are well correlated with the clinical response to chemotherapy. However, in patients treated with immunotherapy, such criteria are less accurate, as already demonstrated in the treatment of metastatic melanoma, but not yet in other malignant tumors.

Therefore, we hope with this study, to identify more accurate imaging criteria that could help oncologists to make optimal decisions for treatment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interest of iRECIST Radiological Assessment for Disease Control Rate (DCR) for Evaluation of Patients With Metastatic Colorectal Cancer dMMR and / or MSI Treated With Nivolumab and Ipilimumab. A GERCOR Open-label Phase II Study NIPICOL C17-01
Actual Study Start Date : December 4, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental arm
Therapy induction (12 weeks) Nivolumab (IV) and Ipilimumab (IV) - every 21 days - 4 cycles Then Nivolumab (IV) alone every 15 days - 20 cycles - until 12 months
Drug: Ipilimumab 200 MG in 40 ML Injection

Induction therapy (12 weeks):

Nivolumab 3mg/kg intravenously (IV) over 60 minutes and Ipilimumab 1mg/kg (IV) over 90 minutes Q3W


Drug: Nivolumab 10 MG/ML

Induction therapy (12 weeks) :

Nivolumab 3mg/kg intravenously (IV) over 60 minutes and Ipilimumab 1mg/kg (IV) over 90 minutes Q3W

Maintenance therapy (40 weeks):

Nivolumab monotherapy IV over 60 minutes Q2W until iRECIST progression or if no PD for one year.





Primary Outcome Measures :
  1. Disease Control Rate (DCR) [ Time Frame: At 12 weeks ]
    According with RECIST 1.1 and iRECIST


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: PFS is defined as time from date of first dose of study treatment to date of first Progression (accordance with RECIST 1.1 or iRECIST) or death due to any cause - Up to 24 months ]
    According with RECIST and iRECIST

  2. Overall Response Rate (ORR) [ Time Frame: Up to 24 months ]
    According with RECIST and iRECIST

  3. Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time between the date of the first dose of study treatment and the death date

  4. Toxicity according to NCI-CTCAE version 4.0 (National Cancer Institute Common Terminology Criteria for Adverse Events), [ Time Frame: Up to 24 months ]
    Patients will be assessed for AEs every visits and evaluations, PD, and treatment discontinuation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed and dated informed consent,
  2. For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug,
  3. Men and women are required to use adequate birth control during the study (when applicable):

    Within the frame of this study, female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control (i.e., pregnancy rate of less than 1% per year) during the period of treatment and for 5 months for women and 7 months for men from the last treatment administration. Men must refrain from donating sperm during this same period.

    Contraceptive methods that result in a low failure rate when used consistently and correctly include methods such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intrauterine devices, intrauterine hormone-releasing stem, true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female partner who is not of childbearing potential or a male partner who has had a vasectomy. Women and female partners using hormonal contraceptive must also use a barrier method i.e. condom or occlusive cap (diaphragm or cervical/vault caps).

    A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).

  4. Histologically proven metastatic adenocarcinoma of the colon and/or rectum,
  5. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
  6. dMMR DNA (protein expression by ICH and/or MSI by PCR):

    • Tumor MMR and/or MSI will be assessed per local guidelines: ICH with two (anti-MLH1 and anti-MSH2) or four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and/or PCR (with PROMEGA: BAT25, BAT26, NR21, NR24, NR27]) by the investigators prior to screening,
    • In ICH, the extinction of MLH1 (+/- PMS2), or MSH2 (+/- MSH6), or MSH6, or PMS2 alone is necessary for inclusion (dMMR),
    • In PCR, we recommended pentaplex panel (BAT25, BAT26, NR21, NR24, and NR27). Tumor samples with instability in 0, 1, or ≥2 markers were identified as MSS, MSI-L, and MSI-H, respectively. Only tumor samples with ≥2 instable markers are necessary for inclusion (MSI-H).

    Agreement of the SPONSOR (GERCOR) will be mandatory to include a patient. GERCOR will check every patient's file to confirm the dMMR/ MSI-H patient's status before inclusion (an anonymized fax. The confirmation of a patient's allocation will be immediately sent by mail to the investigator).

  7. Age ≥18 years,
  8. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1,
  9. Progression during, after, or who are intolerant or have contraindication to approved standard therapies for the metastatic disease which must include at least:

    • Fluoropyrimidine, and oxaliplatin and irinotecan.
    • Anti-EGFR therapy if wild-type RAS and RAF and anti-VEGF therapy,
  10. Hematological status: absolute neutrophil count (ANC) ≥1.5x109/L; platelets ≥100x109/L; hemoglobin ≥9g/dL,
  11. Adequate renal function: serum creatinine level <150µM,
  12. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline phosphatase <5xULN, alanine aminotransferase (ALAT) and aspartame aminotransferase (ASAT) ≤3.0x ULN (≤5.0x ULN for patients with liver involvement of their cancer),
  13. Registration in a National Health Care System (CMU included),
  14. Subjects must have measurable disease per RECIST 1.1. Subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately,
  15. Subject willing to comply to provide primary and metastatic tumor tissue (archival or fresh biopsy specimen), including possible pre-treatment biopsy, for PD-L1 expression analysis and other biomarker correlative studies,
  16. At least one target lesion on CT,
  17. No contraindication to Iodine contrast media injection during CT

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study entry:

  1. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
  2. Unresolved toxicity higher than Grade 1, NCI-CTCAE v 4.03, attributed to any prior therapy
  3. Treatment with any investigational medicinal product within 28 days prior to study entry,
  4. Major surgical procedure within 4 weeks prior to initiation of study treatment,
  5. Other serious and uncontrolled non-malignant disease (including active infection),
  6. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
  7. Pregnant or breastfeeding women,
  8. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.

    Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.

  9. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,
  10. Human immunodeficiency virus (HIV),
  11. Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) or hepatitis C virus (HCV), Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.

    Note: Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA).

  12. Administration of a live, attenuated vaccine within four weeks prior to start of treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study,
  13. Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents,
  14. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within four weeks or five half-lives of the drug, whichever is shorter, prior to start of maintenance treatment,
  15. Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
  16. Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of maintenance treatment, or requirement for systemic immunosuppressive medications during the remainder of the study. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

Note: Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the Medical Monitor.

Note: Subjects are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Adrenal replacement steroid doses including doses >10 mg daily prednisone are permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03350126


Contacts
Contact: Thierry ANDRE, MD +33 (0)1 49 28 29 54 thierry.andre@aphp.fr

Locations
France
Institut Sainte Catherine Not yet recruiting
Avignon, France
Principal Investigator: Laurent MINEUR, MD         
CHRU Besançon Recruiting
Besançon, France
Principal Investigator: Christophe BORG, MD         
Henri Mondor Hospital Recruiting
Créteil, France
Principal Investigator: Christophe TOURNIGAND, MD         
IHFB Recruiting
Levallois-Perret, France
Principal Investigator: Benoist CHIBAUDEL, MD         
Centre Leon Berard Not yet recruiting
Lyon, France
Principal Investigator: Christelle DE LA FOUCHARDIERE, MD         
CHU Nantes - Hôtel Dieu Recruiting
Nantes, France
Principal Investigator: Jaafar BENNOUNA, MD         
Hospital Saint Antoine Recruiting
Paris, France, 75012
Principal Investigator: Romain COHEN, MD         
CHU Poitiers Not yet recruiting
Poitiers, France
Principal Investigator: David TOUGERON, MD         
Sponsors and Collaborators
GERCOR - Multidisciplinary Oncology Cooperative Group
Bristol-Myers Squibb
Investigators
Principal Investigator: Thierry ANDRE, MD Hopital Saint Antoine

Responsible Party: GERCOR - Multidisciplinary Oncology Cooperative Group
ClinicalTrials.gov Identifier: NCT03350126     History of Changes
Other Study ID Numbers: NIPICOL C17-01
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GERCOR - Multidisciplinary Oncology Cooperative Group:
MSI or MMR

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Nivolumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs