AIPAC (Active Immunotherapy PAClitaxel): A multicentre, Phase IIb, randomised, double blind, placebo-controlled study in hormone receptor-positive metastatic breast carcinoma patients receiving IMP321 (LAG-3Ig fusion protein) or placebo as adjunctive to a standard chemotherapy treatment regimen of paclitaxel.
- Conditions
- hormone receptor-positive metastatic breast carcinomametastatic breast cancer10006291
- Registration Number
- NL-OMON55556
- Lead Sponsor
- Immutep S.A.S.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 44
1. Able to give written informed consent and to comply with the protocol
2.1 Metastatic oestrogen receptor positive and/or progesterone receptor
positive breast adenocarcinoma,
histologically proven by biopsy of the primary tumour and/or a metastasis
3. Female of age 18 years or above
4. Patients who are indicated to receive first line chemotherapy with weekly
paclitaxel
5.1 All patients of childbearing potential must have a negative highly
sensitive pregnancy test at
screening and agree to use highly effective method for contraception according
to the EU Clinical
Trial Facilitation Group guidance from time of study entry until at least 6
months after the last
administration of study drug. The partners of patients with childbearing
potential must also apply
contraceptive methods. Patients who are either,
o postmenopausal (>= 60 years of age, or < 60 years of age and amenorrhoeic for
12 months in the
absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression with
folliclestimulating
hormone (FSH) above 40 U/L and oestradiol below 30 ng/L; or if taking tamoxifen
or toremifene, and age < 60 years, then FSH and oestradiol in the
postmenopausal range),
permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy),
o or otherwise be incapable of pregnancy are not considered to be of
childbearing potential
6. ECOG performance status 0-1
7. Expected survival longer than three months
8. Resolution of toxicity of prior therapy to grade < 2 (except for alopecia
and transaminases in case of
liver metastases)
9. Evidence of measurable disease as defined by RECIST version 1.1
10.1 Laboratory criteria:
* Total white cell count >= 3 x 10^9/L
* Platelet count >= 100 x 10^9/L
* Haemoglobin >= 9 g/dL or 5.58 mmol/L
* Absolute Neutrophil Count (ANC) >= 1.5 x 10^9/L
* Serum creatinine <= 1.5 × ULN
* Total bilirubin <= 20 µmol/L, except for familial cholaemia (Gilbert*s disease)
* Serum ASAT and ALAT <= 3 times ULN or <=5 times ULN if liver metastases are
present
1. Prior chemotherapy for metastatic breast adenocarcinoma
2. Disease-free interval of less than twelve months from the last dose of
adjuvant chemotherapy
3. Prior high-dose chemotherapy requiring hematopoietic stem cell rescue
4.1 Inflammatory carcinoma at time of screening
5.1 Candidate for treatment with trastuzumab (or other Her2/neu targeted
agents) or endocrine based
therapy according to the applicable treatment guidelines
6.2 Systemic chemotherapy, radiation therapy or any other investigational agent
within 4 weeks,
endocrine therapy within 1 week or CDK4/6 inhibitors within 5 times half-life
(acc. to SPC) prior
to first dose of study treatment
7.1 Symptomatic known cerebral and/or leptomeningeal metastases
8. Women who are pregnant or lactating
9. Serious intercurrent infection within 4 weeks prior to first dose of study
treatment
10. QTcF >480 ms, family or personal history of long or short QT syndrome,
Brugada syndrome or
known history of QTc prolongation, or Torsade de Pointes (TdP)
11. Uncontrolled electrolyte disorders that can worsen the effects of a
QTc-prolonging drug (e.g.,
hypocalcaemia, hypokalaemia, hypomagnesemia)
12.1 Evidence of severe or uncontrolled cardiac disease (NYHA III-IV) within 6
months prior to first
dose of study treatment including: myocardial infarction, severe/unstable
angina, ongoing cardiac
dysrhythmias of NCI CTCAE version 4.03 Grade >=2, atrial fibrillation,
coronary/peripheral artery
bypass graft, symptomatic congestive heart failure, cerebrovascular accident
including transient
ischemic attack, ventricular arrhythmias requiring medication or symptomatic
pulmonary embolism
13. Active acute or chronic infection
14. Active autoimmune disease requiring immunosuppressive therapy
15.1 Positive test for HIV
16.1 Positive test for Hepatitis B (anti-HBc) or C (Patients who are anti-HBc+
and HBsAg negative are eligible and are not excluded from participation in this
study)
17. Life threatening illness unrelated to cancer
18. Previous malignancies within the last three years other than breast
carcinoma, except successfully
treated squamous cell carcinoma of the skin, superficial bladder cancer, and in
situ carcinoma of the
cervix
19. Any current disorder that would impede the patient*s ability to provide
informed consent or to
comply with the protocol
20. Any condition requiring continuous systemic treatment with either
corticosteroids (>10 mg daily
prednisone equivalents) or other immunosuppressive medications within 4 weeks
prior to first dose
of study treatment. Inhaled or topical steroids and physiological replacement
doses of up to 10 mg
daily prednisone equivalent are permitted in the absence of active autoimmune
disease
21. Past history of severe allergic episodes and/ or Quincke*s oedema
22. Alcohol or substance abuse disorder
23. Known hypersensitivity to any of the components of the study agents
24.1 Participation in an interventional clinical study within 4 weeks prior to
first dose of study
treatment, with intervention not covered by exclusion criterion 6.2
25. Unwilling or unable to follow protocol requirements
26. In the clinical judgment of the Investigator, the patient is unsuitable for
participation in this study
27. Persons with any kind of dependency on the Investigato
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression Free survival</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Efficacy Endpoints<br /><br>* To assess overall survival (OS)<br /><br>* To assess adverse events according to the current National Cancer Institute<br /><br>(NCI) Common Terminology Criteria for Adverse Events (CTCAE) and other safety<br /><br>parameters<br /><br>* To assess the time to next treatment (TTNT), objective response rate (ORR)<br /><br>according to RECIST 1.1, time to and duration of response and duration of<br /><br>stable disease<br /><br>* To assess the plasma concentration time profile of IMP321 and derived PK<br /><br>parameters<br /><br>* To assess the quality of life (QOL)<br /><br>* To assess development of anti-drug (IMP321) antibodies (ADA)</p><br>