Clinical Trials /

Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types

NCT03012581

Description:

This is a Phase 2, non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in 6 cohorts of patients with specific rare cancers who have unresectable locally advanced or metastatic disease, which is resistant or refractory to standard therapy, or for which standard therapy does not exist, or is not considered appropriate, and for which no other experimental treatment options are available.

Related Conditions:
  • Adnexal Carcinoma
  • Basal Cell Carcinoma
  • Head and Neck Carcinoma
  • Malignant Salivary Gland Neoplasm
  • Malignant Solid Tumor
  • Non-Clear Cell Renal Cell Carcinoma
  • Squamous Cell Carcinoma of the Penis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types
  • Official Title: Secured Access to Nivolumab for Adult Patients With Selected Rare Cancer Types

Clinical Trial IDs

  • ORG STUDY ID: UC0105/1611
  • SECONDARY ID: 2016-002257-37
  • NCT ID: NCT03012581

Conditions

  • Carcinoma, Renal Cell
  • Head and Neck Neoplasm
  • Skin Neoplasms
  • Microsatellite Instability
  • Penile Neoplasms

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab

Purpose

This is a Phase 2, non-randomised, open-label, multicentric study to investigate the efficacy and safety of nivolumab monotherapy in 6 cohorts of patients with specific rare cancers who have unresectable locally advanced or metastatic disease, which is resistant or refractory to standard therapy, or for which standard therapy does not exist, or is not considered appropriate, and for which no other experimental treatment options are available.

Detailed Description

      The study plans to enrol up to 250 patients in total with between 20 and 50 patients assigned
      to each cohort according to indication, as follows:

        -  Cohort 1: Non-clear cell RCC

        -  Cohort 2: Rare head and neck cancer

        -  Cohort 3: Rare skin cancer

        -  Cohort 4: MSI-nonCRC

        -  Cohort 5: Penile cancer

        -  Cohort 6: POLE exonucleasic domain mutated cancer

      The study will use a two-stage Bayesian enrichment design. The first stage treats all
      patients from the different cohorts with the investigational product and identifies possibly
      sensitive indications. The second stage will compare outcomes among subsets of patients in
      the identified cohorts to distinguish between subpopulations of patients who may benefit from
      the treatment and patients for whom there is no evidence of efficacy.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalNivolumab 240 mg IV over 60 minutes every 14 days.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patient information sheet and written informed consent form signed.

          2. Histologically confirmed diagnosis of a pathology corresponding to one of the
             following selected cancer types:

               -  Non-clear cell renal-cell carcinomas: papillary renal cell carcinoma (pRCC, type
                  I, type II and non-classified pRCC), chromophobe RCC (ChRCC), renal medullary
                  carcinoma (RMC), collecting duct/Bellini duct carcinoma (CDC),
                  microphthalmia-associated transcription (MiT) family translocation renal cell
                  carcinoma (tRCC), renal cell carcinoma with a prominent sarcomatoid component
                  (sarcRCC).

               -  Rare head and neck cancers: principal and accessory salivary gland tumours,
                  facial tissue tumours.

               -  Rare skin cancers: adnexal carcinomas, basal cell carcinoma resistant to
                  vismodegib.

               -  Non-colorectal cancers with microsatellite instability determined locally by
                  immunohistochemistry or polymerase chain-reaction (PCR)

               -  Squamous cell carcinoma of penis.

               -  Any non MSI-high cancer with POLE exonucleasic domain mutation (somatic or
                  germline) in hotspots (codons 286, 411, 424 and 459) or other germline or somatic
                  variants with high probability of pathogenesis according to in silico assessment
                  by the INCa ad hoc biology group.

          3. Metastatic disease or unresectable locally advanced malignancy that is resistant or
             refractory to standard therapy or for which standard therapy does not exist or is not
             considered appropriate by the Investigator.

          4. Aged ≥ 18 years old.

          5. Measurable disease according to RECIST v1.1 guidelines for solid tumours (Eisenhauer,
             2009).

          6. Able to provide a formalin fixed/paraffin embedded (FFP)E biopsy sample of a
             metastatic site or primitive tumour tissue.

             Note: Patients for whom suitable archived biopsy material is not available must be
             willing to undergo a biopsy of a tumour lesion prior to study entry, unless this is
             medically contraindicated (e.g. site inaccessible or patient safety concerns).

          7. Patients must have a mandatory treatment-free interval of at least 21 days following
             previous systemic anti-cancer treatments.

          8. Patients who have received previous systemic anticancer treatment and/or radiotherapy
             should have recovered from any treatment related toxicity, to a level of ≤ grade 1
             (according to NCI-CTCAE criteria, v 4.0) with the exception of Grade 2 alopecia.

          9. Adequate hematologic function (absolute neutrophil count [ANC] ≥ 1.0 x109/L, platelets
             ≥ 100 x109/L, haemoglobin (Hb) ≥ 9 g/L) measured within 14 days of treatment
             initiation.

         10. Adequate renal function (creatinine clearance ≥ 50 mL/ using the MDRD or CKI EPI
             method) measured within 14 days of treatment initiation.

         11. Adequate hepatic function (serum bilirubin ≤ 1.5 x the reference upper limit of normal
             (ULN) unless due to Gilbert's syndrome; aspartate aminotransferase [ASAT] and alanine
             aminotransferase [ALAT] ≤ 2,5 xULN) measured within 14 days of treatment initiation.
             For patients with documented liver metastasis ASAT/ALAT ≤ 5x ULN is acceptable.

         12. Strictly normal blood levels of calcium and magnesium, measured within 14 days of
             treatment initiation.

         13. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 (Oken, 1982).

         14. Estimated life expectancy ≥ 90 days.

         15. Patients who are sexually active must agree to use a medically accepted method of
             contraception (e.g. implants, injectables, combined oral contraceptives, some
             intrauterine devices or vasectomized partner, for participating women; condoms for
             participating men) or practice complete abstinence, beginning 14 days before the first
             administration of investigational product (IP), while on treatment and for at least 5
             months after the last administration of IP for female patients, and 7 months after the
             last administration of IP for male patients.

         16. Women of childbearing potential must have a negative urine or serum pregnancy test
             within 72 hours prior to the first administration of IP. If urine test results are
             positive or cannot be confirmed as negative, a serum pregnancy test will be required.

         17. Women who are breastfeeding should discontinue nursing prior to the first
             administration of IP and for at least 90 days after the last administration of IP.

         18. Patients must be affiliated to a Social Security System or equivalent.

        Exclusion Criteria:

          1. Prior treatment with an anti-PD1 or anti-PD-L1 antibody

          2. Eligible, and willing, to participate in a clinical trial of an alternative anticancer
             therapy targeting their disease which is open to accrual in France.

          3. Concurrent steroid medication at a dose greater than prednisone 10 mg/day or
             equivalent.

          4. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          5. History of (non-infectious) pneumonitis that required steroids, or current
             pneumonitis.

          6. History of severe hypersensitivity reaction to any monoclonal antibody therapy

          7. Radiotherapy (except for brain and extremities) within 21 days prior to the first
             administration of IP.

          8. Treatment with other investigational drugs or participation in another clinical trial
             within 21 days prior to the first administration of IP or concomitantly with the
             trial.

          9. Has known symptomatic central nervous system (CNS) metastases. Patients with
             previously treated brain metastases may participate provided they are stable (without
             evidence of progression by imaging for at least four weeks prior to the first dose of
             trial treatment and any neurologic symptoms have returned to baseline), have no
             evidence of new or enlarging brain metastases, and are not using steroids for at least
             7 days prior to trial treatment.

         10. Has known carcinomatous meningitis or a history of leptomeningeal disease.

         11. Serum creatinine > 1.5 xULN or glomerular filtration rate (GFR) < 50 ml/min.

         12. Other malignancies within the past 5 years other than basal cell skin cancer or
             carcinoma in situ of the cervix.

         13. Active serious infections in particular if requiring systemic antibiotic or
             antimicrobial therapy.

         14. Active or chronic hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV)
             infection (HIV 1/2 antibodies), or a known history of active Tuberculosis bacillus.

         15. Has received a live vaccine within 30 days of planned start of study treatment. Note:
             Seasonal influenza vaccines for injection are generally inactivated vaccines and are
             allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated
             vaccines, and are not allowed.

         16. Active alcohol or drug abuse.

         17. Psychological, familial, sociological or geographical factors potentially hampering
             compliance with the study protocol and follow-up schedule.

         18. Any condition which in the Investigator's opinion makes it undesirable for the subject
             to participate in the trial or which would jeopardize compliance with the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:measured at the first scheduled disease assessment following study treatment initiation (Day 84, ± 7 days)
Safety Issue:
Description:ORR will be assessed per cohort by an IRC according to RECIST v1.1.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From date of inclusion until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Safety Issue:
Description:Assessed according to RECIST v1.1
Measure:Overall survival
Time Frame:From date of inclusion until the date of death from any cause, assessed up to 36 months
Safety Issue:
Description:
Measure:Best response
Time Frame:From inclusion up to 36 months
Safety Issue:
Description:Assessed according to RECIST v1.1
Measure:Response duration
Time Frame:from first observation of objective response until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Safety Issue:
Description:Assessed according to RECIST v1.1
Measure:Time to response
Time Frame:from inclusion first observation of objective response, assessed up to 36 months
Safety Issue:
Description:Assessed according to RECIST v1.1
Measure:Frequency and severity of adverse events
Time Frame:from inclusion until 100 days after last dose of investigational product
Safety Issue:
Description:assessed according to the NCI-CTCAE v4
Measure:Objective response rate in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
Time Frame:measured at the first scheduled disease assessment following study treatment initiation (Day 84, ± 7 days)
Safety Issue:
Description:ORR will be assessed per cohort by an IRC according to RECIST v1.1.
Measure:Progression-free survival in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
Time Frame:From date of inclusion until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 months
Safety Issue:
Description:Assessed according to RECIST v1.1.
Measure:Overall survival in subgroups of subjects with high versus low expression (cutoff set at the median for the population measured) of different immune markers (PD-L1, CD4+, FOXP3+, Fas-L, OX40, VEGF, CD31; CD34)
Time Frame:From date of inclusion until the date of death from any cause, assessed up to 36 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:UNICANCER

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