Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of mDCF in Combination or Not With Atezolizumab in Advanced Squamous Cell Anal Carcinoma (SCARCE)

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: NCT03519295
Recruitment Status : Recruiting
First Posted : May 8, 2018
Last Update Posted : June 26, 2019
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
GERCOR - Multidisciplinary Oncology Cooperative Group

Brief Summary:

SCARCE is a non-comparative randomized, 2:1 phase II study. The purpose of this study is to assess the progression-free survival rate at 12 months. (evaluation according with RECISTv1.1 criteria).

For all patients, CT scan will be planned at baseline, and every 8 weeks until 12 months from randomization (or disease progression), and every 12 weeks thereafter.

PET scan will be performed at baseline, at the end of mDCF treatment, and at 12 months after randomization (in absence of disease progression).

CT scan and PET scan will be collected for a centralized review.


Condition or disease Intervention/treatment Phase
Anal Cancer Drug: MPDL3280A Drug: mDCF Phase 2

Detailed Description:

Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, its incidence increases worldwide and no standard therapy is currently available to treat metastatic or relapsing cases. SCCA is mostly induced by human papillomavirus (HPV) infections with HPV-related oncoproteins (E6 and E7) expressed in more than 90% of cases.

Based on the preliminary results of the Epitope-HPV02 study and although it provide proof of concept data on taxane-based chemotherapy efficacy in SCCA, complete responses observed after 6-8 cycles of chemotherapy has not translated into long-term remissions .

Combining immunogenic chemotherapy with anti-PD-1/PD-L1 might be a convenient way to increase the diversity of antigens released by tumor and T cells.

So for the SCARCE study, we hypothesized that combination of mDCF (8 cycles) with MPDL32801 (12 months) might induce synergy and improve the rate of long-term PFS rate.

The aim of the SARCE study is to provide a valuable proof of concept to establish immunogenic chemotherapy and anti-PDL1 as a standard of care for SCCA patients with poor clinical outcomes and to take advantage of the presence of HPV antigens in most patients (HPV 16 and 18 genotypes are involved in 90% of SCCA) to set up a specific immunomonitoring program based on tumor samples and blood-derived lymphocytes to better understand the potential synergisms between immunogenic chemotherapy and anti-PDL1 and to identify valuable biomarkers of treatment efficacy.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Non-comparative Randomized 2:1 Phase II Study of Docetaxel, Cisplatin, and 5-fluorouracil in Combination or Not With Atezolizumab in Patients With Metastatic or Unresectable Locally Advanced Squamous Cell Anal Carcinoma
Actual Study Start Date : July 3, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anal Cancer

Arm Intervention/treatment
Experimental: ARM A - mDCF + Atezolizumab
  • MPDL3280A (atezolizumab) will be administered every 2 weeks at 800 mg for 12 months.
  • Patients will receive 8 cycles of mDCF (docetaxel 40 mg/m2 day 1, cisplatin 40 mg/m2 day 1 and 5FU at 1200 mg/m2/day for 2 days) every 2 weeks
Drug: MPDL3280A
MPDL3280A (atezolizumab) will be administered every 2 weeks at 800 mg for 12 months.

Drug: mDCF
Patients will receive 8 cycles of mDCF (docetaxel 40 mg/m2 day 1, cisplatin 40 mg/m2 day 1 and 5FU at 1200 mg/m2/day for 2 days) every 2 weeks

Active Comparator: ARM B - mDCF
Patients will receive 8 cycles of mDCF (docetaxel 40 mg/m2 day 1, cisplatin 40 mg/m2 day 1 and 5FU at 1200 mg/m2/day for 2 days) every 2 weeks.
Drug: mDCF
Patients will receive 8 cycles of mDCF (docetaxel 40 mg/m2 day 1, cisplatin 40 mg/m2 day 1 and 5FU at 1200 mg/m2/day for 2 days) every 2 weeks




Primary Outcome Measures :
  1. Progression free survival rate (PFS) [ Time Frame: at 12 months ]
    PFS will be defined as the time interval between the date of randomization and the date of first progression (local, regional, metastatic, second cancer) or death regardless of the cause. Patients alive without progression will be censored at the time of the latest news


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: within 3 years after the initiation of the treatment ]
    OS will be calculated between the date of randomization and the date of death from any cause. . Alive patients or lost to follow-up at the time of the analysis will be censored at the date of last follow-up.

  2. Progression free survival [ Time Frame: within 3 years after the initiation of the treatment ]
    PFS will be defined as the time interval between the date of randomization and the date of first progression (local, regional, metastatic, second cancer) or death regardless of the cause

  3. Quality of life related to heath [ Time Frame: From the randomization to patient death or for maximum 3 years ]
    EORTC-QLQ-C30

  4. Objective response rate (ORR) [ Time Frame: within 3 years after the initiation of the treatment ]
    Evaluated by RECIST criteria version 1.1

  5. Tolerance graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] criteria v4.03 [ Time Frame: within 3 years after the initiation of the treatment ]
    graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] criteria v4.03



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.


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

Inclusion Criteria:

  1. Male or female, aged ≥18 years,
  2. Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) ≤1,
  3. Histologically proven and unresectable locally advanced recurrent or metastatic squamous cell anal carcinoma,
  4. Presence of a target lesion on CT-scan assessed by RECIST v1.1 criteria,
  5. Patient eligible to the mDCF regimen,
  6. CT scan performed within 28 days prior inclusion,
  7. PET scan performed within 28 days prior inclusion,
  8. Signed and dated informed consent,
  9. Patient affiliated to or beneficiary of French social security system,
  10. Ability to comply with the study protocol, in the Investigator's judgment,
  11. Life expectancy ≥ 6 months,
  12. Adequate hematologic and end-organ function.
  13. Previous concomitant chemoradiotherapy is permitted if completed before 28 days of starting treatment.

Exclusion Criteria:

Non-eligibility to clinical trials if one of the following parameter is reported:

  1. Previously received chemotherapy for metastatic disease,
  2. Previously received cisplatin except for concomitant chemoradiotherapy,
  3. Previously received taxanes (paclitaxel or docetaxel) or another spindle poison (navelbine) in the treatment of SCCA,
  4. Previously received anti-tumor immunotherapy (HPV vaccination is allowed),
  5. Previous radiotherapy within 28 days of randomization (14 days if radiotherapy of bone metastases)
  6. Diagnosis of additional malignancy within 3 years prior to the randomization with the exception for curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer,
  7. Any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study,
  8. Current participation in a study of an investigational agent or in the period of exclusion,
  9. Pregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration, men must refrain from donating sperm during this same period.
  10. Patient under guardianship, curatorship or under the protection of justice.

    Non-eligible to chemotherapy:

  11. Inadequate organ functions: uncontrolled cardiac condition, known cardiac failure, unstable coronaropathy, respiratory failure, and Chronic Obstructive Pulmonary Disease (COPD),
  12. Diabetes with vascular or neurovascular complications,
  13. Preexistent peripheral neuropathy or impaired audition,
  14. HIV positive with CD4 count under 400 cells/mm3 (VIH test is mandatory before inclusion),
  15. Active hepatitis B or C virus (HBV or HCV) infection (chronic or acute), (Defined as having a positive HBV surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total HBV core antibody (HBcAb) test at screening, are eligible for the study. HCV infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test),
  16. Active tuberculosis,
  17. Concomitant treatment with CYP3A4 inhibitor like ritonavir, indinavir, or ketoconazole, etc. Replacement by another drug before randomization, whenever is possible, is allowed,
  18. Known hypersensitivity or contraindication to any of the study chemotherapy drugs (taxanes, cisplatin, 5FU), according with the SmPC of each drug
  19. Uncontrolled infection or another life-risk condition,
  20. Known hearing impairment that contraindicates cisplatin administration,
  21. Administration of a live (attenuated) vaccine within 28 days of planned start of study therapy of known need for this vaccine during treatment,
  22. Administration of prophylactic phenytoin,
  23. Inadequate laboratory values: creatinine clearance (CrCl by Modification of Diet in Renal Disease [MDRD] formula) <60 ml/min, neutrophil count <1500 /mm3, platelets <100000/mm3, bilirubin 2.5 x upper limit of normal (ULN), aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 x ULN or 5 x ULN with liver metastasis.
  24. Patient with known dihydropyridine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to a fluoropyrimidine-containing regimen, or in case of clinically significant active heart disease or myocardial infarction within 6 months or if patient treated with sorivudine or its clinically related analogues, such as brivudine

    Non-eligible to immunotherapy:

  25. Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy,
  26. Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed.

    Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, (see Annex 7 for a more comprehensive list of autoimmune diseases and immune deficiencies) with the following exceptions:

  27. Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study,
  28. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study,
  29. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

    • Rash must cover < 10% of body surface area,
    • Disease is well controlled at baseline and requires only low-potency topical corticosteroids,
    • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months,
  30. Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
  31. Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed,
  32. Previously received an anti-PD1, anti-PDL1, or anti-CTLA4 agent,
  33. Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of atezolizumab formulation,
  34. History of colorectal inflammatory disease,
  35. History of idiopathic or secondary pulmonary fibrosis (history of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy,
  36. Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study,
  37. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia,
  38. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

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): NCT03519295


Contacts
Layout table for location contacts
Contact: Stefano KIM, MD 03 81 47 99 99 stefanokim@gmail.com

Locations
Layout table for location information
France
Clinique de l'Europe Not yet recruiting
Amiens, France
Principal Investigator: Khadija KALAï, MD         
Institut Sainte Catherine Not yet recruiting
Avignon, France
Principal Investigator: Laurent MINEUR, MD         
CHRU Jean Minjoz Recruiting
Besançon, France, 25000
Contact: Stefano KIM, MD         
CHU Bordeaux - Hôpital Haut Lévêque Recruiting
Bordeaux, France
Contact: Denis SMITH         
Centre François Baclesse Recruiting
Caen, France
Contact: Aurélie PARZY, MD         
Hôpitaux Civils de Colmar Not yet recruiting
Colmar, France
Principal Investigator: Gilles BREYSACHER, MD         
Clinique des Cèdres Not yet recruiting
Cornebarrieu, France
Principal Investigator: Alain LEDIT, MD         
GHPSO Creil Not yet recruiting
Creil, France
Principal Investigator: Elisabeth CAROLA, MD         
Centre Georges François Leclerc Recruiting
Dijon, France
Contact: françois GHIRINGHELLI, MD         
Institut Hospitalier Franco-Britannique Not yet recruiting
Levallois-Perret, France
Principal Investigator: Benoist CHIBAUDEL, MD         
Centre Oscar Lambert Recruiting
Lille, France
Contact: Farid EL HAJBI, MD         
Centre Léon Bérard Recruiting
Lyon, France
Contact: Christelle de la Fouchardière, MD         
Hôpital Jean Mermoz Recruiting
Lyon, France
Contact: Jérôme DESRAME, MD         
CHU Timone Recruiting
Marseille, France
Principal Investigator: Laëtitia DAHAN, MD         
Hopital Montbéliard Recruiting
Montbéliard, France
Contact: Christophe BORG, MD         
ICM Val d'Aurelle Recruiting
Montpellier, France
Contact: Emmanuelle SAMALIN, MD         
CHU Nantes Not yet recruiting
Nantes, France
Principal Investigator: Jaafar BENNOUNA, MD         
Centre Antoine Lacassagne Recruiting
Nice, France
Contact: Eric FRANCOIS, MD         
Hôpital Saint Antoine Recruiting
Paris, France, 7514
Contact: Daniel LOPEZ TRABADA ATAZ         
Groupe Hospitalier Diaconesses Crois Saint Simon Recruiting
Paris, France
Principal Investigator: Olivier DUBREUIL, MD         
Groupe Hospitalier Saint Joseph Recruiting
Paris, France
Contact: Nabil BABA HAMED, MD         
Hôpital Européen Georges Pompidou Recruiting
Paris, France
Contact: Simon PERNOT         
Hôpital Henri Mondor Not yet recruiting
Paris, France
Contact: Isabelle BAUMGAERTNER, MD         
Hôpital saint Louis Recruiting
Paris, France
Contact: Nelson LOURENCO, MD         
Insitut Curie Recruiting
Paris, France
Contact: Bruno BUECHER         
Centre CARIO Not yet recruiting
Plérin, France
Principal Investigator: Pierre Luc ETIENNE, MD         
CHU Poitiers Not yet recruiting
Poitiers, France
Principal Investigator: David TOUGERON, MD         
CHU Robert Debré Reims Recruiting
Reims, France
Contact: Olivier BOUCHE, MD         
CH Saint Quentin Not yet recruiting
Saint-Quentin, France
Principal Investigator: Innoncenti DADAMESSI, MD         
Centre Paul Strauss Recruiting
Strasbourg, France
Contact: Meher BENABDELGHANI, MD         
CHU Tours Not yet recruiting
Tours, France
Principal Investigator: Thierry LECOMTE, MD         
Sponsors and Collaborators
GERCOR - Multidisciplinary Oncology Cooperative Group
Roche Pharma AG

Layout table for additonal information
Responsible Party: GERCOR - Multidisciplinary Oncology Cooperative Group
ClinicalTrials.gov Identifier: NCT03519295     History of Changes
Other Study ID Numbers: SCARCE C17-02
First Posted: May 8, 2018    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Epidermoid Cancers of the Anal Canal
Additional relevant MeSH terms:
Layout table for MeSH terms
Anus Neoplasms
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Cisplatin
Docetaxel
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs