To determine the Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of CriPec® docetaxel monotherapy in subjects with ovarian cancer who are resistant to prior platinum-based therapy.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the Objective Response Rate (ORR) as assessed by Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of CriPec® docetaxel
monotherapy in subjects with ovarian cancer who are resistant to prior
platinum-based therapy.
Secondary outcome
* To evaluate the safety and tolerability of CriPec® docetaxel according to
NCI-CTCAE criteria (version 5.0)
* To evaluate the clinical activity of CriPec® docetaxel as measured by:
o Progression free survival (PFS) at 6 months based on RECIST version 1.1 and
combined assessment using Gynecological Cancer Intergroup (GCIG) definitions
for CA-125
o GCIG CA-125 response criteria
o Duration of response (DOR) based on RECIST version 1.1 and combined
assessment using GCIG definitions for CA-125
o Time to progression (TTP)
o Disease control rate (DCR)
Background summary
Cristal Therapeutics has developed a proprietary technology (CriPec®) to
transform drug molecules into biodegradable nanoparticle compounds, thereby
creating nanomedicines designed to improve the therapeutic profile of drugs.
Based on this technology, the nanoparticle CriPec® docetaxel has been developed
by conjugating docetaxel to a linker agent. This docetaxel-linker conjugate is
thereafter temporarily covalently entrapped in a stabilized, ~65 nm sized
CriPec® nanoparticle. By the nature of its distribution and pharmacokinetic
(PK) profile after administration, CriPec® docetaxel is designed to have an
improved efficacy and safety balance compared to conventionally administered
docetaxel (Taxotere®) commonly used as treatment in solid tumors.
A Phase I trial in subjects with solid tumors has determined a RP2D of CriPec®
docetaxel of 60 mg/m2 given every 3 weeks (Q3W) with corticosteroid
premedication.
The proposed Phase IIa exploratory 2-stage clinical study aims to investigate
the safety and efficacy of CriPec® docetaxel in subjects with platinum
resistant ovarian cancer.
Study objective
To determine the Objective Response Rate (ORR) as assessed by Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of CriPec® docetaxel
monotherapy in subjects with ovarian cancer who are resistant to prior
platinum-based therapy.
Study design
This is a single-arm, Phase IIa exploratory trial to assess the efficacy,
safety and tolerability of CriPec® docetaxel monotherapy administered
intravenously (IV) Q3W to subjects with ovarian cancer that are resistant to
prior platinum-based therapy. Subjects will be treated with the RP2D of 60
mg/m2 of CriPec® docetaxel that was determined in the Phase I trial with
corticosteroid premedication (CT-CL01), until disease progression, unacceptable
toxicity, or discontinuation for any other reason. The end of trial is defined
as the time point when all subjects have either discontinued trial treatment or
received more than six cycles of treatment, whichever occurs sooner. Any
subject eligible for further treatment cycles at that time may continue to
receive further treatment cycles with CriPec® docetaxel until discontinuation
or withdrawal.
Intervention
Once every 3 weeks intravenous infusion with CriPec® docetaxel for a maximum of
6 cycles.
Study burden and risks
The possible, as yet unknown, side effects of CriPec® docetaxel.
Blood collection: After a blood test, pain, bleeding, a bruise on the puncture
site or thrombosis can occur, problems usually disappear. Incidents may also
occur: fainting, the puncture site may become inflamed, reddened or become
irritated. If blood is taken regularly, it can cause anemia, which may require
a blood transfusion. If a lot of blood is taken in one day, it is done with a
special needle for infusions, which only needs to be inserted once instead of
several times. Introducing this needle involves risks, such as infections,
bleeding and mild discomfort and bruising at the puncture site.
CT scans: radiation exposure. The extra radiation falls within the limit values
**set for this type of exposure to extra radiation. There is a very small risk
that a CT scan will cause problems.
For some CT / MRI scans it is necessary that a contrast agent is injected.
There is a small risk of an allergic reaction to the contrast agent. This
reaction can be mild (itching, rash, nausea) or severe (breathing problems or
shock) Most allergic reactions can be brought under control with medication.
The contrast agent can also cause dehydration or damage to the kidneys, which
in the worst case leads to kidney failure.
Ecg: possible skin reaction on the electrodes on the chest. This irritation
usually disappears as soon as the electrodes have been removed.
Oxfordlaan 55
Maastricht 6229 EV
NL
Oxfordlaan 55
Maastricht 6229 EV
NL
Listed location countries
Age
Inclusion criteria
1. Age * 18 years.
2. Histologically or cytologically confirmed diagnosis of epithelial ovarian,
fallopian or peritoneal cancer.
3. Platinum-resistant recurrent epithelial ovarian cancer (defined as
progression within 6 months after last platinum dose).
4. Subjects who have received a maximum of 2 prior treatment lines, of which
one could have been taxane-based.
5. Measurable disease according to RECIST version 1.1. Only CA-125 progression
without any clinical or radiological progression is not allowed.
6. Performance status (WHO scale/ECOG) * 1 (Appendix 1).
7. Estimated life expectancy of at least 5 months.
8. Toxicities incurred as a result of previous anti-cancer therapy (radiation
therapy, chemotherapy, or surgery) must be resolved to * Grade 2 (as defined by
NCI- CTCAE version 5.0).
9. ANC * 1.5 x 109/L; platelets * 100 x 109/L; haemoglobin * 5.58 mmol/L (*
9.00 g/dL).
10. Creatinine * 1.75 x Upper Limit of Normal (ULN) and estimated creatinine
clearance * 30 mL/min according to Cockcroft-Gault formula; Serum albumin
levels > 25g/L
11. Serum bilirubin * 1.5 x ULN except for subjects with Will Gilbert*s
syndrome, alkaline phosphatase, ASAT and ALAT * 2.5 x ULN, unless related to
liver metastases, in which case * 5 x ULN is allowed.
12. Written informed consent according to local guidelines.
Exclusion criteria
1. Subjects with platinum-refractory disease. Refractory disease is defined by
subjects who progressed during the preceding treatment or within 4 weeks after
last dose of platinum containing therapy.
2. Less than four weeks since the last treatment with other anti-cancer
therapies, (i.e. endocrine therapy, immunotherapy, radiotherapy, chemotherapy,
etc.); less than eight weeks for cranial radiotherapy, and less than six weeks
for nitrosoureas and mitomycin C prior to first study treatment.
3. Current or recent (within 28 days of first study treatment) treatment with
another investigational drug or participation in another investigational study.
4. Active or symptomatic brain metastases. Subjects must be on a stable or
decreasing dose of corticosteroids and/or have no requirement for
anticonvulsants for five days prior to Cycle 1 day1 (C1D1).
5. Current malignancies other than epithelial ovarian, fallopian or peritoneal
cancer, with exception of adequately treated cone-biopsied in situ carcinoma of
the cervix uteri and basal or squamous cell carcinoma of the skin.
6. Major surgical procedure (including open biopsy, excluding central line IV
and portacath) within 28 days prior to the first study treatment, or
anticipation of the need for major surgery during the course of the study
treatment.
7. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100mm Hg).
8. Grade * 2 motor or sensory neuropathy symptoms (as defined by CTCAE version
5.0).
9. Known hypersensitivity to any of the study drugs or excipients or taxanes.
10. Any skin toxicity in the medical history of the subject of Grade * 2
associated with impaired skin integrity (skin toxicity defined as any form of
rash, HFS, skin ulceration, toxic epidermal necrolysis, eczema) or any skin
toxicity for which systemic treatment was needed.
11. Clinically significant (i.e. active) cardiovascular disease defined as
stroke, transient ischemic attack (TIA) or myocardial infarction within * 6
months prior to first trial treatment.
12. Subjects, who are pregnant or breastfeeding. Serum pregnancy test to be
performed within 7 days prior to study treatment start in subjects of
childbearing potential.
13. Absence of highly effective method of contraception as of C1D1 in female
subjects of childbearing potential (defined as < 2 years after last
menstruation and not surgically sterile).
14. Known hypersensitivity to dexamethasone or any other reason that would make
the subject not eligible to receive dexamethasone.
15. Evidence of any other medical conditions (such as psychiatric illness,
infectious diseases, drug or alcohol abuse, physical examination or laboratory
findings) that may interfere with the planned treatment, affect subject
compliance or place the subject at high risk from treatment-related
complications.
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 | EUCTR2018-002117-36-NL |
| ClinicalTrials.gov | NCT03742713 |
| CCMO | NL66572.091.18 |