NeoplasmsPhase 1NCT03521037
Rucaparib Hepatic Impairment Study in Patients With a Solid Tumor
A Phase 1 study testing Rucaparib camsylate in people with Neoplasms, run by pharmaand GmbH at 6 sites in 3 countries.
Trial summary
Phase 1, open-label, parallel group, PK, safety and tolerability study in patients with an advanced solid tumor and either normal hepatic function (Group 1, n = 8) or moderate hepatic impairment (Group 2, n = 8) according to the NCI-ODWG criteria. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Rucaparib camsylate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 27 Feb 2018to 24 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All Patients:
- Patients ≥18 years of age at the time the ICF is signed;
- Patients with a histologically or cytologically confirmed advanced solid tumor who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
- ECOG PS less than or equal to 2
- Adequate bone marrow and renal function
- Hepatically Impaired Patients (in addition):
Show all 10Show fewer
- Stable hepatic impairment as judged by the Investigator
- Moderate Hepatic Impairment (NCI-ODWG criteria) during Screening
- Patients with Normal Hepatic Function (in addition):
- Normal Hepatic Function (NCI-ODWG criteria)
Who cannot join
- All Patients:
- Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or investigational drugs within 14 days prior to day 1
- Ongoing toxicity ≥ Grade 2 per Common Terminology Criteria for Adverse Events criteria (CTCAE version 4.03)
- Prior treatment with any poly adenosine diphosphate ribose polymerase inhibitor
- Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, stenting or poorly controlled hypertension within the last 3 months prior to Screening
- Pre-existing duodenal stent, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
Show all 16Show fewer
- Hospitalization for bowel obstruction within 3 months prior to Day 1
- Untreated or symptomatic central nervous system (CNS) metastases
- Evidence or history of bleeding disorder
- Acute illness within 14 days prior to Day 1
- Active second malignancy
- Hepatically Impaired Patients (in addition):
- Severe hepatic encephalopathy (Grade >2);
- History of liver transplantation;
- Advanced ascites or ascites that require drainage and albumin supplementation, as judged by the Investigator;
- Acute damage of the liver with Grade 4 AST/ALT values
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Poland4 sites
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
Biała Podlaska, 21-500
Med Polonia Sp. z o.o.
Poznan, 60-693
Zachodniopomorskie Centrum Onkologii w Szczecinie
Szczecin, 71-730
BioVirtus Centrum Medyczne
Warsaw, 02-681
United Kingdom1 site
Northern Centre for Cancer Care
Newcastle upon Tyne, NE7 7DN
About this study
Official title: A Phase 1, Open-Label, Parallel Group Study to Determine the Pharmacokinetics, Safety and Tolerability of Rucaparib in Patients With an Advanced Solid Tumor and Either Moderate Hepatic Impairment or Normal Hepatic Function
Phase 1, open-label, parallel group, PK, safety and tolerability study in patients with an advanced solid tumor and either normal hepatic function (Group 1, n = 8) or moderate hepatic impairment (Group 2, n = 8) according to the NCI-ODWG criteria. Patients in Group 1 and Group 2 may be enrolled in parallel, with preferential enrollment of Group 2 patients before Group 1 patients. The study will consist of 2 parts: a single-dose PK part (Part I) and a continuous rucaparib treatment part (Part II).
Read the detailed description
In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles. The starting dose for all Group 1 patients will be 600 mg BID. The first 2 patients with moderate hepatic impairment (Group 2) that enter Part II will receive a starting dose of 400 mg BID rucaparib; a lower dose of rucaparib may also be set based on PK results observed in Part I. If this initial starting dose is determined to be safe and tolerable as determined by real-time PK data and dose limiting toxicities (DLT) observed during the first 28 days of rucaparib, the starting dose of rucaparib may be increased in subsequent Group 2 patients. The starting dose for Group 2 patients may also be lowered, based on the patients' real time PK and emerging safety data. The Sponsor and key clinical research organization (CRO) staff will review available adverse event, laboratory, and PK data to determine the starting dose for subsequent Group 2 patients, as well as allowing intra-patient dose escalation of rucaparib after Cycle 1.Treatment with rucaparib will continue until progression of disease, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or other appropriate clinical reason for discontinuation.
- Conditions
- Neoplasms
- Being tested
- Rucaparib camsylate
- Keywords
- rucaparib, CO-338, Clovis, Clovis Oncology, PARP inhibitor, hepatic impairment
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rucaparib camsylateDrug
Also called rubraca
In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles.
| Study group | Role | What they receive |
|---|---|---|
| no name | Experimental | Group 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment Receives: Drug: Rucaparib camsylate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum plasma rucaparib concentration (Cmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Secondary outcomes (12)
Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Terminal half-life (t1/2) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Time to attain maximum plasma rucaparib concentration (Tmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Apparent clearance (CL/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Apparent volume of distribution during terminal phase (Vz/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: day 1 to day 7
Trough plasma concentration of rucaparib at steady state (Cmin,ss)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Measured: approximately 4 months
Renal clearance (CLR) of rucaparib
PK parameter of rucaparib to be calculated from the plasma and urine concentration-time data
Measured: day 1 to day 2
Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on urine concentration-time data
Measured: day 1 to day 2
Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on the amount of rucaparib recovered in urine
Measured: day 1 to day 2
Incidence of Adverse Events [Safety and Tolerability]
Measured: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of clinical laboratory abnormalities [Safety and Tolerability]
Measured: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of dose modifications [Safety and Tolerability]
Measured: From Day 1 to last patient visit in Part II (approximately 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2018
- Study start27 Feb 2018
- Primary completion27 Sep 2019
- Study completion24 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- pharmaand GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03521037
- Sponsor's protocol ID
- CO-338-078
- Status last verified
- Jun 2023
- First submitted
- 14 Feb 2018
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Parallel Group Study to Determine the Pharmacokinetics, Safety and Tolerability of Rucaparib in Patients With an Advanced Solid Tumor and Either Moderate Hepatic Impairment or Normal Hepatic Function
- ClinicalTrials.gov ID
- NCT03521037
- Acronym / sponsor ID
- CO-338-078
- Conditions
- Neoplasms
- Keywords
- rucaparib, CO-338, Clovis, Clovis Oncology, PARP inhibitor, hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- pharmaand GmbHIndustry (pharma, biotech, devices)
- Study start
- 27 Feb 2018 (actual)
- Primary completion
- 27 Sep 2019 (actual)
- Study completion
- 24 Feb 2021 (actual)
- First posted
- 11 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1, open-label, parallel group, PK, safety and tolerability study in patients with an advanced solid tumor and either normal hepatic function (Group 1, n = 8) or moderate hepatic impairment (Group 2, n = 8) according to the NCI-ODWG criteria. Patients in Group 1 and Group 2 may be enrolled in parallel, with preferential enrollment of Group 2 patients before Group 1 patients. The study will consist of 2 parts: a single-dose PK part (Part I) and a continuous rucaparib treatment part (Part II).
Detailed description
In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles. The starting dose for all Group 1 patients will be 600 mg BID. The first 2 patients with moderate hepatic impairment (Group 2) that enter Part II will receive a starting dose of 400 mg BID rucaparib; a lower dose of rucaparib may also be set based on PK results observed in Part I. If this initial starting dose is determined to be safe and tolerable as determined by real-time PK data and dose limiting toxicities (DLT) observed during the first 28 days of rucaparib, the starting dose of rucaparib may be increased in subsequent Group 2 patients. The starting dose for Group 2 patients may also be lowered, based on the patients' real time PK and emerging safety data. The Sponsor and key clinical research organization (CRO) staff will review available adverse event, laboratory, and PK data to determine the starting dose for subsequent Group 2 patients, as well as allowing intra-patient dose escalation of rucaparib after Cycle 1.Treatment with rucaparib will continue until progression of disease, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or other appropriate clinical reason for discontinuation.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| no name | Experimental | Drug: Rucaparib camsylateGroup 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients ≥18 years of age at the time the ICF is signed;
- Patients with a histologically or cytologically confirmed advanced solid tumor who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
- ECOG PS less than or equal to 2
- Adequate bone marrow and renal function
- Stable hepatic impairment as judged by the Investigator
Key exclusion criteria (16 listed)
- Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or investigational drugs within 14 days prior to day 1
- Ongoing toxicity ≥ Grade 2 per Common Terminology Criteria for Adverse Events criteria (CTCAE version 4.03)
- Prior treatment with any poly adenosine diphosphate ribose polymerase inhibitor
- Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, stenting or poorly controlled hypertension within the last 3 months prior to Screening
- Pre-existing duodenal stent, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rucaparib camsylateAlso: rubracaIn Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles. | Drug | no name |
Primary outcome
Maximum plasma rucaparib concentration (Cmax)
Time frame: day 1 to day 7
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last)
Time frame: day 1 to day 7
PK parameter of rucaparib to be calculated from the plasma concentration-time data
12 secondary outcomes
Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)
Time frame: day 1 to day 7
Terminal half-life (t1/2) of rucaparib
Time frame: day 1 to day 7
Time to attain maximum plasma rucaparib concentration (Tmax)
Time frame: day 1 to day 7
Apparent clearance (CL/F) of rucaparib
Time frame: day 1 to day 7
Apparent volume of distribution during terminal phase (Vz/F) of rucaparib
Time frame: day 1 to day 7
Trough plasma concentration of rucaparib at steady state (Cmin,ss)
Time frame: approximately 4 months
Renal clearance (CLR) of rucaparib
Time frame: day 1 to day 2
Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose
Time frame: day 1 to day 2
Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose
Time frame: day 1 to day 2
Incidence of Adverse Events [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of clinical laboratory abnormalities [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)
Incidence of dose modifications [Safety and Tolerability]
Time frame: From Day 1 to last patient visit in Part II (approximately 2 years)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rucaparib camsylate in people with Neoplasms, run by pharmaand GmbH at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Poland, Slovakia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum plasma rucaparib concentration (Cmax) (time frame: day 1 to day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.