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

  • STATUS
    Recruiting
  • End date
    Jun 2, 2022
  • participants needed
    99
  • sponsor
    GERCOR - Multidisciplinary Oncology Cooperative Group
Updated on 2 February 2021
Investigator
Stefano KIM, MD
Primary Contact
CH Saint Quentin (0.0 mi away) Contact
+37 other location
carcinoma
chemoradiotherapy
anal carcinoma
mpdl3280a

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.

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.

Details
Condition Rectal Cancer, Anal Cancer, anal carcinoma
Treatment MPDL3280A, mDCF
Clinical Study IdentifierNCT03519295
SponsorGERCOR - Multidisciplinary Oncology Cooperative Group
Last Modified on2 February 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Male or female, aged 18 years
Performance status Eastern Cooperative Oncology Group World Health Organization (ECOG-WHO) 1
Histologically proven and unresectable locally advanced recurrent or metastatic squamous cell anal carcinoma
Presence of a target lesion on CT-scan assessed by RECIST v1.1 criteria
Patient eligible to the mDCF regimen
CT scan performed within 28 days prior inclusion
PET scan performed within 28 days prior inclusion
Signed and dated informed consent
Patient affiliated to or beneficiary of French social security system
Ability to comply with the study protocol, in the Investigator's judgment
Life expectancy 6 months
Adequate hematologic and end-organ function
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
Previously received chemotherapy for metastatic disease
Previously received cisplatin except for concomitant chemoradiotherapy
Previously received taxanes (paclitaxel or docetaxel) or another spindle poison (navelbine) in the treatment of SCCA
Previously received anti-tumor immunotherapy (HPV vaccination is allowed)
Previous radiotherapy within 28 days of randomization (14 days if radiotherapy of bone metastases)
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
Any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
Current participation in a study of an investigational agent or in the period of exclusion
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
Patient under guardianship, curatorship or under the protection of justice
Non-eligible to chemotherapy
\. Inadequate organ functions: uncontrolled cardiac condition, known cardiac
failure, unstable coronaropathy, respiratory failure, and Chronic Obstructive
Pulmonary Disease (COPD)
\. Diabetes with vascular or neurovascular complications
\. Preexistent peripheral neuropathy or impaired audition
\. HIV positive with CD4 count under 400 cells/mm3 (VIH test is mandatory
before inclusion)
\. 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)
\. Active tuberculosis
\. Concomitant treatment with CYP3A4 inhibitor like ritonavir, indinavir, or
ketoconazole, etc. Replacement by another drug before randomization, whenever
is possible, is allowed
\. Known hypersensitivity or contraindication to any of the study
chemotherapy drugs (taxanes, cisplatin, 5FU), according with the SmPC of each
drug
\. Uncontrolled infection or another life-risk condition
\. Known hearing impairment that contraindicates cisplatin administration
\. Administration of a live (attenuated) vaccine within 28 days of planned
start of study therapy of known need for this vaccine during treatment
\. Administration of prophylactic phenytoin
\. 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
\. 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
\. Any immunosuppressive therapy (i.e. corticosteroids >10mg of
hydrocortisone or equivalent dose) within 14 days before the planned start of
study therapy
\. Active autoimmune disease that has required a systemic treatment in past
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, Sjgren syndrome
Guillain-Barr syndrome, or multiple sclerosis, (see Annex 7 for a more
comprehensive list of autoimmune diseases and immune deficiencies) with the
following exceptions
\. Patients with a history of autoimmune-related hypothyroidism who are on
thyroid replacement hormone are eligible for the study
\. Patients with controlled Type 1 diabetes mellitus who are on an insulin
regimen are eligible for the study
\. 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
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