IMP321 Phase 1 Study in Advanced or Metastatic Renal Cell Carcinoma Patients (P003)
18 Years
N/A
Both
Stage IV Renal Cell Carcinoma
Trial Information
IMP321 Phase 1 Study in Advanced or Metastatic Renal Cell Carcinoma Patients (P003)
This is a single-center, single-arm, open label, non-randomized, fixed dose-escalation,
phase 1 study, performed in ambulatory and day-hospital setting. After a screening period,
patients will enter a drug administration period, followed by a 'post-study' period.
Four IMP321 dose levels, 50 µg, 250 µg, 1.250 mg, 6.250 mg and 30 mg will be evaluated in
successive cohorts of patients. At any given dose level 3 patients will be administered one
subcutaneous dose every 2 weeks for a total of 12 weeks (6 injections in total), separated
by 13-day administration-free intervals.
The next (higher) dose level will be dosed to 3 new patients if the previous dose level has
been well tolerated. Investigator will decide whether the safety is acceptable by performing
an evaluation after the third administration (at week 8) and if the next patients can be
included.
The successive cohorts of patients are summarized as follows:
- Cohort A will correspond to a group of 3 patients receiving the 50 µg dose. If safety
at this dose level is acceptable as evaluated a fortnight after the 6-week
administration, the following cohort will be undertaken.
- Cohort B will correspond to a group of 3 patients receiving the 250 µg dose. If safety
at this dose level is acceptable as evaluated a fortnight after the 6-week
administration, the following cohort will be undertaken.
- Cohort C will correspond to a group of 3 patients receiving the 1,250 µg dose. If
safety at this dose level is acceptable as evaluated a fortnight after the 6-week
administration, the following cohort will be undertaken.
- Cohort D will correspond to a group of 3 patients receiving the 1,250 µg dose. If
safety at this dose level is acceptable as evaluated a fortnight after the 6-week
administration, the following cohort will be undertaken.
- Cohort E will correspond to a group of 3 patients receiving the 6,250 µg dose. The
patients will receive their first administration one-by-one with a two-weeks interval.
If safety at this dose level is acceptable as evaluated a fortnight after the 6-week
administration for the last patient, the following cohort will be undertaken.
- Cohort F will correspond to a group of 3 patients receiving the 6,250 µg dose. If the
tolerability of this dose level has been judged acceptable in cohort E, the three
patients will receive their first IMP321 injection simultaneously.
- Cohort G will correspond to a group of 3 patients receiving the 30,000 µg dose. The
patients will receive their first IMP321 administration one-by-one with a two-weeks
interval (+/- 5 days). If safety at this dose level is acceptable as evaluated a
fortnight after the 6-week administration for the last patient, the following cohort
will be undertaken.
- Cohort H will correspond to a group of 3 patients receiving the 30,000 µg dose. If the
tolerability of this dose level has been judged acceptable in cohort E, the three
patients will receive their first IMP321 injection simultaneously.
Once the main period of study has been completed, namely two weeks after a cohort is
completed, i.e. at week 14, all patients will undergo an ambulatory 'post-study'
examination.
Patients of the Cohort B, C, E, F and G will participate in a pharmacokinetic (PK) study and
all patients in a pharmacodynamic (PD) study involving additional blood samples.
Inclusion Criteria:
- Patient with metastatic renal clear cell (MRCC) adenocarcinoma, histologically proven
by biopsy of the primary tumor and/or a metastasis. Prior nephrectomy is not
required. The patient will be included in the study only if an efficacious cancer
treatment can not be proposed.
- Patient to whom the currently available anticancer treatments are contra-indicated.
- Male or female 18 years or above. NB: Women must be either post-menopausal, rendered
surgically sterile or practicing a reliable method of contraception (hormonal,
intrauterine device or barrier). Pregnant women are excluded from this study.
- ECOG performance status 0-1.
- Expected survival longer than three months.
- Total white cell count ≥ 3.109/L.
- Platelet count ≥ 100.109/L.
- Hemoglobin > 9 g/dL or > 5.58 mmol/L.
- Serum creatinine < 160 µmol/L.
- Total bilirubin < 20 mmol/L, except for familial cholemia (Gilbert's disease)
- Serum ASAT and ALAT < 3 times the upper limit of normal or < 5 times upper limit of
normal if liver metastases are present.
- Able to give written informed consent and to comply with the protocol.
Exclusion Criteria:
- Pregnancy, lactation or lack of effective contraception in fertile women of
childbearing potential.
- Serious intercurrent infection within the 30 days prior to first administration.
- Known clinically active autoimmune disease.
- Known B or C active hepatitis.
- Known HIV positivity.
- Life threatening illness unrelated to cancer.
- Known cerebral metastases.
- Previous malignancies within the last two years other than successfully treated
squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated with
cone biopsy.
- Previous history of major psychiatric disorder requiring hospitalization or any
current psychiatric disorder that would impede the patient's ability to provide
informed consent or to comply with the protocol.
- Corticosteroids unless used as substitutive therapy.
- Past history of severe allergic episodes and/or Quincke edema.
- Past or present history of any organic disorder likely to modify absorption,
distribution or elimination of the study drug.
- Alcohol or substance abuse disorder.
- IL-2 therapy or any other investigational agent within 30 days of first
administration.
- Chemotherapy or radiotherapy within the past 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to first administration of the study drug or lack of recovery from
adverse events (to grade 1 or less toxicity according to CTCAE 3.0) due to agents
administered more than 4 weeks earlier. Exception is made regarding the x-ray
treatment for painful bone metastases.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Evaluate clinical and laboratory safety and tolerability profiles
Outcome Time Frame:
3 months
Safety Issue:
Yes
Principal Investigator
Bernard Escudier, M.D
Investigator Role:
Principal Investigator
Investigator Affiliation:
Gustave Roussy, Cancer Campus, Grand Paris
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
P003
NCT ID:
NCT00351949
Start Date:
September 2005
Completion Date:
October 2008
Related Keywords:
- Stage IV Renal Cell Carcinoma
- Advanced or metastatic renal cell carcinoma
- IMP321
- Monotherapy
- LAG-3
- CD223
- Carcinoma
- Carcinoma, Renal Cell
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