Breast CancerPhase 1REVIVALNCT02418624
Phase I of Carboplatin-Olaparib Followed by Olaparib Monotherapy in Advanced Cancer
A Phase 1 study testing carboplatin, olaparib in people with Breast Cancer and Ovarian Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
Trial summary
A phase I trial to determine the recommended phase two dose of the combination of carboplatin and olaparib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Ovarian Cancer, Advanced Cancer
- What is being tested?
- carboplatin, olaparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2015to Jan 2019
- 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
- Histological or cytological proof of advanced 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 olaparib-carboplatin combination therapy (prior (neo-)adjuvant chemotherapy is accepted and does not count as one line, since administered in early stage disease);
- Age ≥ 18 years;
- Able and willing to give written informed consent;
- WHO performance status of 0, 1 or 2;
- Able and willing to undergo blood sampling for PK and PD analysis;
- Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
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- Evaluable disease according to RECIST 1.1 criteria;
- Minimal acceptable safety laboratory values
- ANC of ≥ 1.5 x 10^9 /L
- Hemoglobin of at least 6.2 mM and no transfusions in the last 28 days.
- Platelet count of ≥ 100 x 10^9 /L
- Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN (or < 3 x ULN in case of known Gilbert syndrome), ASAT and ALAT 2.5 x ULN (or <5 x ULN in case of liver metastasis)
- Renal function as defined by serum creatinine ≤1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
- Negative pregnancy test (urine/serum) for female patients with childbearing potential;
Who cannot join
- 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;
- Patients who have received high dose alkylating agents, a PARP1 inhibitor or carboplatin pretreatment; unless no progression on carboplatin had been observed during earlier treatment and the last carboplatin administration had been longer than 6 months ago;
- Any current treatment with drugs that induce or inhibit the CYP3A4 system : http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#inVivo or APPENDIX IX
- Women who have a positive pregnancy test (urine/serum) and/or who are 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)
- Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1x8 Gy for pain palliation then a seven days interval should be maintained;
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- Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
- Patients with known active hepatitis B or C;
- Recent myocardial infarction (< six months) or unstable angina;
- Symptomatic brain metastases. If adequately treated with resection and/or irradiation and patients are at least four weeks completely free of symptoms of these metastases and without medication related to these metastases patients could be eligible if all other in- and exclusion criteria are obeyed.
- Known leptomeningeal metastases.
- Patients with myelodysplastic syndrome or acute myeloid leukemia
- Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, 1066CX
About this study
Official title: A Phase I Followed by a Randomized Phase II Trial of Two Cycles Carboplatin-Olaparib Followed by Olaparib Monotherapy Versus Capecitabine in BRCA-1 or -2 Mutated Her2 Negative Advanced Breast Cancer as First Line Treatment
A phase I trial to determine the recommended phase two dose of the combination of carboplatin and olaparib.
Read the detailed description
A 3+3 dose escalation trial of 2 cycles (21 days) carboplatin and olaparib combination therapy, followed by olaparib monotherapy until progression or unacceptable toxicity in patients with advanced cancer.
- Conditions
- Breast Cancer, Ovarian Cancer, Advanced Cancer
- Being tested
- carboplatin, olaparib
- Keywords
- breast cancer 1, early onset (BRCA1), breast cancer 2, early onset (BRCA2), homologous recombination deficiency, carboplatin, olaparib
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms, Fanconi Anemia, Complementation Group D1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatin, olaparibDrug
2 cycles of carboplatin and olaparib combination therapy followed by olaparib monotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | carboplatin, olaparib Receives: Drug: carboplatin, olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
The dose level at which more than 1/6 patients develop a dose limiting toxicity
Measured: per doselevel of 3 to 6 patients (when 3-6 patients have completed DLT period of 3 weeks)
Secondary outcomes (3)
Pharmacokinetics (area under time-concentration curve (AUC))
Pharmacokinetics (PK) measurements of olaparib alone and olaparib in combination with carboplatin
Measured: 1 year
Pharmacodynamics (PAR (Poly(ADP) ribose) activation measured with the PAR assay)
PAR (Poly(ADP) ribose) activation measured with the PAR assay
Measured: 1 year
Objective Response Rate
Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sabine Linn, MD, PhD, Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418624
- Sponsor's protocol ID
- M14REV
- Other IDs
- NL50610.031.14, 2013-005590-41
- Acronym
- REVIVAL
- Status last verified
- Jan 2019
- First submitted
- 9 Mar 2015
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Schouten PC, Dackus GM, Marchetti S, van Tinteren H, Sonke GS, Schellens JH, Linn SC. A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial. Trials. 2016 Jun 21;17(1):293. doi: 10.1186/s13063-016-1423-0.
PubMed 27323902
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Followed by a Randomized Phase II Trial of Two Cycles Carboplatin-Olaparib Followed by Olaparib Monotherapy Versus Capecitabine in BRCA-1 or -2 Mutated Her2 Negative Advanced Breast Cancer as First Line Treatment
- ClinicalTrials.gov ID
- NCT02418624
- Acronym / sponsor ID
- REVIVAL / M14REV
- Conditions
- Breast Cancer, Ovarian Cancer, Advanced Cancer
- Keywords
- breast cancer 1, early onset (BRCA1), breast cancer 2, early onset (BRCA2), homologous recombination deficiency, carboplatin, olaparib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 16 Apr 2015 (estimated)
- 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.
A phase I trial to determine the recommended phase two dose of the combination of carboplatin and olaparib.
Detailed description
A 3+3 dose escalation trial of 2 cycles (21 days) carboplatin and olaparib combination therapy, followed by olaparib monotherapy until progression or unacceptable toxicity in patients with advanced cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: carboplatin, olaparibcarboplatin, olaparib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological or cytological proof of advanced 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 olaparib-carboplatin combination therapy (prior (neo-)adjuvant chemotherapy is accepted and does not count as one line, since administered in early stage disease);
- Age ≥ 18 years;
- Able and willing to give written informed consent;
- WHO performance status of 0, 1 or 2;
- Able and willing to undergo blood sampling for PK and PD analysis;
Key exclusion criteria (13 listed)
- 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;
- Patients who have received high dose alkylating agents, a PARP1 inhibitor or carboplatin pretreatment; unless no progression on carboplatin had been observed during earlier treatment and the last carboplatin administration had been longer than 6 months ago;
- Any current treatment with drugs that induce or inhibit the CYP3A4 system : http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#inVivo or APPENDIX IX
- Women who have a positive pregnancy test (urine/serum) and/or who are 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)
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 |
|---|---|---|
| carboplatin, olaparib2 cycles of carboplatin and olaparib combination therapy followed by olaparib monotherapy. | Drug | Dose escalation |
Primary outcome
Maximum Tolerated Dose
Time frame: per doselevel of 3 to 6 patients (when 3-6 patients have completed DLT period of 3 weeks)
The dose level at which more than 1/6 patients develop a dose limiting toxicity
3 secondary outcomes
Pharmacokinetics (area under time-concentration curve (AUC))
Time frame: 1 year
Pharmacodynamics (PAR (Poly(ADP) ribose) activation measured with the PAR assay)
Time frame: 1 year
Objective Response Rate
Time frame: 1 year
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 16 Jan 2019.
- Derived from this study: PubMed 27323902Schouten PC, Dackus GM, Marchetti S, van Tinteren H, Sonke GS, Schellens JH, Linn SC. A phase I followed by a randomized phase II trial of two cycles carboplatin-olaparib followed by olaparib monotherapy versus capecitabine in BRCA1- or BRCA2-mutated HER2-negative advanced breast cancer as first line treatment (REVIVAL): study protocol for a randomized controlled trial. Trials. 2016 Jun 21;17(1):293. doi: 10.1186/s13063-016-1423-0.
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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.
Sabine Linn, MD, PhD principal investigator
The Netherlands Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing carboplatin, olaparib in people with Breast Cancer and Ovarian Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.
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 14 inclusion and 13 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 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 Tolerated Dose (time frame: per doselevel of 3 to 6 patients (when 3-6 patients have completed DLT period of 3 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02418624, which also lists 1 linked publication.
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 16 Jan 2019.