The primary objective of the study is to assess the efficacy and safety of 3 different treatment arms (bevacizumab alone, atezolizumab-bevacizumab combination with acetylsalicylic acid and atezolizumab-bevacizumab combination with placebo) in…
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Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to assess the efficacy and safety of 3
different treatment arms (bevacizumab alone, atezolizumab-bevacizumab
combination with acetylsalicylic acid and atezolizumab-bevacizumab combination
with placebo) in advanced recurrent platinum-resistant ovarian, fallopian tube,
or primarily peritoneal cancer patients in order to select the optimal
treatments for further development in phase III
The outcome parameter is the rate of Progression-Free Survival at 6 months
(PFS-6) according to RECIST v1.1 as assessed by the local investigator.
Secondary outcome
Secundary study parameters: overall survival, progression free survival, second
progression free survival, clinical response, disease control and duration of
response as measured by RECIST v1.1 and irRECIST.
Background summary
Atezolizumab enhances the immune system which inhibits or stops tumour growth.
It blocks PD-L1. Bevacizumab is an antibody that is already approved as a
treatment for ovarian cancer in combination with other chemo therapies. It
inhibits vascular development around the tumour by blocking VEGF (vascular
endothelial growth factor). Review papers indicate that acetylsalicylic acid
(aspirin or ASA) improves the results of these drugs. Therefore, this trial
will investigate the beneficial effect of combining the immune therapeutic
drug, atezolizumab, with bevacizumab (with or without ASA) and also the effect
of bevacizumab only in advanced platinum-resistant ovarian cancer.
Study objective
The primary objective of the study is to assess the efficacy and safety of 3
different treatment arms (bevacizumab alone, atezolizumab-bevacizumab
combination with acetylsalicylic acid and atezolizumab-bevacizumab combination
with placebo) in advanced recurrent platinum-resistant ovarian, fallopian tube,
or primarily peritoneal cancer patients in order to select the optimal
treatments for further development in phase III.
The secondary objectives of the study are to:
* assess the biological activity and immunological effects of each treatment in
the tumor microenvironment and in the peripheral blood
* assess the effect of treatment on disease control and overall survival
Study design
This is a randomized phase II study, aimed at evaluating different
atezolizmab/bevacizumab-based strategies using progression free survival
rates at 6 months (PFS-6) to select the best combination(s) to recommend for a
phase III study, where it will be compared to a standard of care.
Randomization occurs after verification of the eligibility criteria and
informed consent. Patients are randomized centrally (see Section 12) to one of
the 3 treatment options and will be stratified for the following factors:
* Institution
* Number of previous treatment lines
Intervention
Randomized treatment:
Arm 1 bevacizumab 15 mg/kg q3w
Arm 2 atezolizumab 1200 mg flat dose q3w + placebo 320 mg/d - ARM CLOSED
Arm 3 atezolizumab 1200 mg flat dose q3w + acetylsalicylzuur 320 mg/d - ARM
CLOSED
Arm 4 bevacizumab 15 mg/kg q3w + atezolizumab 1200 mg flat dose q3w + placebo
320 mg/d
Arm 5 bevacizumab 15 mg/kg q3w + atezolizumab 1200 mg flat dose q3w +
acetylsalicylzuur 320 mg/d
Cross-over treatment to bevacizumab 15 mg/kg q3w + atezolizumab 1200 mg flat
dose q3w is applicable to one arm only.
Patients will not receive further study treatment, but treated as considered
most appropriate by the treating physician according to clinical practice.
Study burden and risks
The nature and extent of the burden and risks associated with participation in
this trial compared to standard of care consists of a tuberculosis skin test
and a biopsy during the screening period. Eight weeks after the start of the
trial treatment another biopsy is performed. The other interventions are
comparable to standard of care.
Overall, a patient may be spending 4 hours of extra time and may suffer from
the adverse events that come with a tuberculosis skin test and biopsies, such
as a haemorrhage.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
- Recurrent, histologically proven, platinum-resistant, epithelial ovarian,
fallopian tube and primary peritoneal cancer in advanced or metastatic stage.
Histological diagnosis by image guided biopsy, laparoscopy or laparotomy.
Tumors diagnosed on cytology only and borderline tumors are excluded.
- At least one lesion accessible to biopsy without putting patient at risk
- WHO PS: 0-2 for patients having received no more than two previous lines of
therapy. WHO PS: 0-1 for patients having received >2 previous lines of therapy
- Prior chemotherapy or bevacizumab:
* No prior treatment with hyperthermic intraperitoneal chemotherapy
(HIPEC) is allowed
* Any number of platinum-based chemotherapy lines are allowed but a
maximum of 2 previous non-platinum containing lines
* Prior treatment with bevacizumab or other targeted agent against VEGF or
VEGF receptor is allowed, but at least 18 weeks must have elapsed since their
last administration
* Eligible patients with * 2 previous treatment lines must have been
previously exposed to bevacizumab or other targeted agents against VEGF or VEGF
receptor
- Patients may have had prior therapy providing the following conditions are
met:
* Radiation therapy: recovery period of 14 days prior to the first study
treatment; exception: single fraction radiotherapy with the indication of pain
control
* Systemic anti-tumoral treatment: wash-out period of 21 days prior to the
first study treatment
- Recovery from any toxic effects of prior therapy to * Grade 1 per the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
CTCAE v4.0) except fatigue or alopecia
- Absence of any psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol
- Signed Informed Consent Form
Exclusion criteria
- Age < 18 years
- Life expectancy of < 12 weeks
- No adequate hematologic and end-organ function
- Use of acetylsalicylic acid, NSAIDs or other COX-2 inhibitors that cannot be
stopped at baseline and for the whole duration of the study. Occasional use is
allowed.
- History of bowel obstruction related to abdominal fistula, tracheoesophageal
fistula, gastrointestinal perforation or intra-abdominal abscess.
- Clinical symptoms of recent bowel obstruction or paralytic ileus, but
excluding postoperative obstruction (within 4 weeks after abdominal surgery),
or evidence of recto-sigmoid involvement by pelvic examination or bowel
involvement on CT scan
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation
of study treatment, or anticipation of need for such a vaccine during
atezolizumab treatment or within 5 months after the final dose of atezolizumab.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004601-17-NL |
| ClinicalTrials.gov | NCT02659384 |
| CCMO | NL61266.091.17 |