Brief Title
Carboplatin-cyclophosphamide Combined With Atezolizumab
Official Title
A Phase 1b to Assess the Safety and Tolerability of Carboplatin-cyclophosphamide Combined With Atezolizumab, an Antibody That Targets Programmed Death Ligand 1 (PD-L1), in Patients With Advanced Breast Cancer and Gynaecologic Cancer
Brief Summary
This is a single centre, 3+3, dose finding, open label, phase 1b clinical study of
carboplatin and cyclophosphamide, in combination with atezolizumab.
Detailed Description
The starting dose is carboplatin AUC 5mg/ml*min, cyclophosphamide 600mg/m2 and atezolizumab
840 mg, all administered intravenously. One cycle is 28 days. On day 1 carboplatin,
cyclophosphamide and atezolizumab will be administered. On day 15 atezolizumab only will be
administered. Patients will be treated until loss of clinical benefit, unacceptable
toxicities, or withdrawal of consent. It is expected that 6-12 patients will be enrolled,
depending on safety issues observed.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Secondary Outcome
Overall Response Rate
Condition
Breast Cancer
Intervention
carbplatin, cyclophophamide, atezolizumab
Study Arms / Comparison Groups
carbo, cyclo, atezolizumab
Description: The starting dose is carboplatin AUC 5mg/ml*min (d1), cyclophosphamide 600mg/m2(d1) and atezolizumab 840 mg (D1, 15), all administered intravenously
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
12
Start Date
January 2017
Completion Date
October 2021
Primary Completion Date
August 2017
Eligibility Criteria
Inclusion Criteria:
- Histological or cytological proof of advanced breast cancer (M1) or advanced
gynaecological cancer (cervix (M1, FIGO IVA/IVB), ovarian (only after recurrence on
carboplatin and/or paclitaxel) stage 4 cervical or endometrial (T3-T4, FIGO IVA/IVB)
cancer) pre-treated with maximally one line of systemic chemotherapy in the advanced
setting and any line of hormonal therapy for advanced disease and potentially
benefitting from carboplatin-cyclophosphamide and atezolizumab. (prior (neo-)adjuvant
chemotherapy is accepted and does not count as one line, since administered in early
stage disease);
- Men and women >= 18 years;
- Able and willing to give written informed consent;
- WHO performance status of 0 or 1;
- Life expectancy >= 3 months, allowing adequate follow up of toxicity evaluation and
antitumor activity;
- Minimal acceptable safety laboratory values
Exclusion Criteria:
- Any treatment with investigational drugs within 28 days prior to receiving the first
dose of investigational treatment; or 21 days for standard (neo-)adjuvant
chemotherapy, hormonal and immunotherapy;
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies.
- Women who have a positive pregnancy test (urine or serum) and/or who ware breast
feeding;
- Unreliable contraceptive methods. Women and men enrolled in this trial must agree to
use a reliable contraceptive method throughout the study (adequate contraceptive
methods are: oral, injected or implanted hormonal methods, intra-uterine devices or
systems, condom or other barrier contraceptive measures, sterilization and true
abstinence);
- Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2
type patients;
- Positive test for HIV
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HbsAg]
test at screening) or active hepatitis C Patients with past hepatitis B virus (HBV)
infection or resolved HBV infection (defined as having a negative HBsAg test and a
positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
chain reaction (PCR) is negative for HCV RN
- Active tuberculosis
- Receipt of a live, attenuated vaccine within 28 days prior to enrolment or
anticipation that such a live, attenuated vaccine will be required during the study
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
anti-CTLA-4 (like Ipilimumab), anti-PD-1 (like pemprolizumab), or anti-PD-L1
therapeutic antibodies (like atezolizumab).
- Treatment with systemic immunostimulatory agents (including but not limited to
interferons or IL-2) within 28 days or five half-lives of the drug (whichever is
shorter) prior to enrolment;
- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 28 days prior to enrolment, or anticipated requirement for systemic
immunosuppressive medications during the trial
- Patients who have received acute, low-dose, systemic immunosuppressant medications
(e.g., one-time dose of dexamethasone for nausea) may be enrolled in the study. The
use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension,
and low-dose supplemental corticosteroids for adrenocortical insufficiency are
allowed;
- Patients with known alcoholism, drug addiction and/or psychiatric of physiological
condition which in the opinion of the investigator would impair study compliance;
- Recent myocardial infarction ( Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT02914470
Organization ID
N16LOG
Responsible Party
Sponsor
Study Sponsor
The Netherlands Cancer Institute
Collaborators
Roche Pharma AG
Study Sponsor
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Verification Date
October 2021