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IMP321 Phase I Study in Metastatic Breast Carcinoma Patients Receiving First-line Paclitaxel

Phase 1
18 Years
Not Enrolling
Metastatic Breast Cancer

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Trial Information

IMP321 Phase I Study in Metastatic Breast Carcinoma Patients Receiving First-line Paclitaxel

This study is an open label, non-randomized, fixed dose-escalation phase I study, performed
in ambulatory setting with patients receiving as a first line chemotherapy for metastatic
breast carcinoma the standard 6 cycles of paclitaxel (80 mg/m² at D1, D8 and D15 of every
4-week cycle). Twenty mg i.v. dexamethasone will be given in the first cycle before each
paclitaxel infusion. Corticosteroids will not be administered after the first chemotherapy
cycle if the first 3 i.v. infusions of paclitaxel have been well tolerated.

Three IMP321 dose levels (0.25, 1.25 and 6.25 mg) will be evaluated in three cohorts of at
lesat 8 patients. At any given dose level the patients will be administered one dose every
two weeks for a total of 24 weeks (12 injections in total), separated by 13-day intervals
free of IMP321 administration.

The study drug will be given by subcutaneous injection:

- Cohort A: 0.25 mg s.c.

- Cohort B: 1.25 mg s.c.

- Cohort C: 6.25 mg s.c.

The repeated single doses will be administered on D2 and D16 of the 4-week cycles, on the
day which follows chemotherapy.

After a screening performed between Week -2 and Day 1, patients will enter the main study
period. Upon having completed the 6 cycles of IMP321 treatment at Week 23, they will have an
ambulatory 'post-study' examination (at Week 25).

Cohort B will be undertaken once the safety and tolerability results of Cohort A have been
satisfactory; the investigator will take his decision for involving the last 8 patients of
the study after the 6th administration (Week 13 assessment) of the fifth patient of Cohort
A. All cohorts will follow the same schedule

Standard clinical and laboratory safety examinations, CT scan and pharmacodynamic (PD) blood
tests will be performed. A complete examination will be carried out at Week 13 (after the
6th drug dosing) and Week 25.

Inclusion Criteria:

- Patients with stage IV breast adenocarcinoma, histologically proven by biopsy of the
primary tumor and/or a metastasis.

- Female not pregnant (or with negative pregnancy test) or male.

- Fertile patients must use effective contraception during and for 3 months after drug

- 18 years or above.

- ECOG performance status 0-1.

- Expected survival longer than three months.

- Resolution of toxicity of prior therapy to grade < 2 (except alopecia).

- With or without prior adjuvant or neoadjuvant chemotherapy (authorized).

- With or without hormone therapy in adjuvant and/or the advanced setting (authorized).

- Evidence of measurable disease as defined by Response Evaluation Criteria in Solid
Tumors (RECIST).

- Biphosphonate therapy must have started at least 4 weeks prior to first dosing of the
study drug.

- Asthma or chronic obstructive pulmonary disease allowed provided daily systemic
corticosteroid therapy is not required.

- 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:

- Prior chemotherapy for metastatic breast adenocarcinoma.

- Disease-free interval < 12 months from last dose of adjuvant chemotherapy.

- Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.

- Inflammatory carcinoma.

- Systemic chemotherapy, hormone or endocrine therapy given as breast cancer therapy
within 30 days prior to first dosing of the study drug.

- Any investigational drug within 30 days prior to first dosing of the study drug.

- Candidate for treatment with trastuzumab or administration of trastuzumab within 30
days prior to first dosing of the study drug.

- Known cerebral or leptomeningeal metastases.

- Pregnancy or breast feeding.

- Serious intercurrent infection within the 30 days prior to first dosing of the study

- Motor or sensory peripheral neuropathy ≥ 2 according to the National Cancer Institute

- Congestive heart failure.

- Active acute or chronic infection.

- Active autoimmune disease requiring immunosuppressive therapy.

- Known HIV positivity.

- Life threatening illness unrelated to cancer.

- Previous malignancies within the last two years other than breast carcinoma,
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 or before each injection of

- 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.

- Radiotherapy within the 30 days prior to first dosing of the study drug.

Type of Study:


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:

6 months

Safety Issue:


Principal Investigator

Maya Gutierrez, M.D

Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre René Huguenin


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

July 2006

Completion Date:

January 2010

Related Keywords:

  • Metastatic Breast Cancer
  • Metastatic breast cancer
  • IMP321
  • hLAG-3Ig
  • LAG-3
  • CD223
  • Chemotherapy
  • Paclitaxel
  • Combination therapy
  • Breast Neoplasms
  • Carcinoma