An open-label Phase I/IIa study to evaluate the safety and efficacy of CCS1477 as monotherapy and in combination, in patients with advanced solid/metastatic tumours.
- Conditions
- Solid/metastatic tumour10027476
- Registration Number
- NL-OMON51947
- Lead Sponsor
- CellCentric Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
1. Written informed consent;
2. willing and and able to comply with study protocol procedures
3. >= 18 years
4. ECOG performance status 0-1 with no deterioration over previous 2 weeks and
minimum life expectancy of 12 weeks
5. Adequate organ functions:
• AST/ALT <=3 x ULN or AST/ALT <=5 x ULN
• Total bilirubin <=1.5 x ULN (or <3 UNL if bilirubin rise is due to Gilbert's
syndrome or of non-hepatic origin, or due to underlying liver involvement).
• Calculated creatinine clearance by Cockcroft-Gault formula >=30 ml/min²
• ANC >=1.5 x 109/L
• Platelets >=100 x 109/L
• Haemoglobin >=9g/dL. (maintained without transfusion within 14 days of
starting CCS1477)
• Normal sodium level (patients with borderline sodium decrease below normal
level may be eligible following discussion with medical monitor).
• Serum albumin >2.5 g/dL
• LDH within normal level (patients with borderline LDH results may be eligible
following discussion with medical monitor)
6. For duration of the study and 1 week after the last study administration,
sexually active male patients must be willing to use barrier contraception with
all sexual partners. Where the sexual partner is a *woman of child-bearing
potential* who is not using effective contraception, men must use a condom and
another form of contraception during the study and for 6 months after the last
dose of study medication.
7. Females must agree to use highly effective contraceptive measures, must not
be breast feeding and must have a negative serum pregnancy test prior to start
of dosing if of child-bearing potential, or must have evidence of
non-child-bearing potential at screening per one of:
• Post menopausal defined as aged more than 50 years and amenorrhoeic for at
least 12 months following cessation of all exogenous hormonal treatments
• Documentation of irreversible surgical sterilisation by hysterectomy,
bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Amenorrhoeic for 12 months and serum FSH, LH and plasma oestradiol levels in
the postmenopausal range for institution
8. Patients must have assessable disease (by CT, MRI, bone scan or X-ray) but
are not required to have measurable disease
Additional inclusion criteria for mCRPC patients (Parts A, B, C, D and F only)
9. Patients must have previously received standard available therapy including
(but not limited to):
• abiraterone and/or enzalutamide (or equivalent anti-androgen), and
• a taxane (unless ineligible)
10. Progressive disease documented by one or more of:
• Biochemical progression defined as at least 2 stepwise increases in a series
of any 3 PSA values collected while the patient has castrate levels of
testosterone. The 3 PSA values selected do not need to be consecutive, and do
not need to include the most recent PSA collected at, or prior to, study
enrolment, but must meet the following criteria:
a. PSA progression defined by minimum of 3 rising PSA levels with an interval
of >=1 week between each determination
b. Each of the 3 PSA values must be collected while the patient is under
medical castration or is surgically castrated
c. Ideally all 3 should be done after anti-androgen withdrawal (if applicable),
but they can be done during the withdrawal period
• Progression as defined by RECIST v1.1 guideline for assessment of malig
All Patients:
1. Intervention with any of the following
• Any chemotherapy, investigational agents or other anti-cancer drugs within 14
days or 5 half-lives (whichever is longer of these two) of the first dose of
study treatment (excludes treatment with immunotherapy agents which must be
assessed on a case by case basis). This does not apply to prior treatment with
abiraterone for patients in Part C1 or C2 or prior treatment with enzalutamide
for patients in Part D1 (except patients in the DDI arm who must have a 4 week
washout of enzalutamide prior to starting the study) and D2.
• Radiotherapy with a wide field of radiation or to more than 30% of the bone
marrow within 4 weeks of the first dose of study treatment
• Major surgical procedure or significant traumatic injury as judged by the
investigator, within 4 weeks of the first dose of study treatment, or have an
anticipated need for major surgery during the study
• Strong inducers of CYP3A4 (See Appendix E) taken within 4 weeks of the first
dose of study treatment or while on study treatment (excluding enzalutamide in
Part D1 and D2 which does not require a 4 week wash-out prior to the first dose
of study treatment, except for patients in the DDI arm).
• Strong inhibitors of CYP3A4 or CYP2C8 or CYP3A4 sensitive substrates (See
Appendix E) taken within 2 weeks of the first dose of study treatment or while
on study treatment.
• Washout periods may be reduced for specific medications (eg. statins)
following discussion with the medical monitor.
• Herbal medications cannot be taken within 7 days of the first dose of study
treatment (4 weeks for St John*s wort) or while on study treatment
• Statins; patients may receive fluvastatin or pravastatin (with monitoring for
potential toxicities), or atorvastatin or simvastatin at 10mg daily dose only.
Patients
• Systemic cancer treatment should not be initiated for at least 30 days after
the last administration of Radium-223 (Ra-223, Xofigo)
2. Any unresolved reversible toxicities from prior therapy greater than Common
Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting
study treatment with the exception of alopecia and neuropathy
3. Female patients who are pregnant or breast-feeding at study entry. Breast
feeding is contraindicated during study treatment and for 1 month after study
drug is discontinued.
4. Any evidence of severe or uncontrolled systemic diseases, including for
example diabetes, uncontrolled hypertension and active bleeding diatheses,
which in the investigator*s opinion makes it undesirable for the patient to
participate in the study or which would jeopardise compliance with the
protocol, or active infection* including hepatitis B, hepatitis C and human
immunodeficiency virus (HIV). *Active viral infection is defined as requiring
antiviral therapy. Screening for chronic conditions is not required
5. Patients with any known uncontrolled inter-current illness including ongoing
or active clinically significant infections, symptomatic congestive heart
failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements. Refractory nausea and vomiting, chronic gastrointestinal diseases
or previous significant bowel resection, with clinica
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary objective<br /><br>To investigate the safety and tolerability of CCS1477 as monotherapy and in<br /><br>combination. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary objectives<br /><br>- To obtain a preliminary assessment of the anti-tumour activity of CCS1477<br /><br>- To characterize the pharmacokinetics (PK) of combination agents when dosed in<br /><br>combination with CCS1477 to investigate any drug-drug interactions.<br /><br><br /><br><br /><br>Exploratory objectives<br /><br>- To explore the relationship between PK, safety, efficacy and blood borne and<br /><br>tissue biomarkers, if appropriate.<br /><br>- To collect and store blood and tumour samples for exploratory biomarker<br /><br>analysis<br /><br>- To investigate the presence, and/or identity of drug metabolites of CCS1477<br /><br>and, if appropriate, characterise their PK. </p><br>