NCT02418624

Brief Summary

A phase I trial to determine the recommended phase two dose of the combination of carboplatin and olaparib.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline
Completed

Started May 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 9, 2015

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 16, 2015

Completed
15 days until next milestone

Study Start

First participant enrolled

May 1, 2015

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2019

Completed
Last Updated

January 16, 2019

Status Verified

January 1, 2019

Enrollment Period

3.7 years

First QC Date

March 9, 2015

Last Update Submit

January 14, 2019

Conditions

Breast CancerOvarian CancerAdvanced Cancer

Keywords

breast cancer 1, early onset (BRCA1)breast cancer 2, early onset (BRCA2)homologous recombination deficiencycarboplatinolaparib

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose

    The dose level at which more than 1/6 patients develop a dose limiting toxicity

    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))

    1 year

  • Pharmacodynamics (PAR (Poly(ADP) ribose) activation measured with the PAR assay)

    1 year

  • Objective Response Rate

    1 year

Study Arms (1)

Dose escalation

EXPERIMENTAL

carboplatin, olaparib

Drug: carboplatin, olaparib

Interventions

carboplatin, olaparibDRUG

2 cycles of carboplatin and olaparib combination therapy followed by olaparib monotherapy.

Dose escalation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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;
  • 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;

You may not qualify if:

  • 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;
  • 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;
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066CX, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 27323902DERIVED

MeSH Terms

Conditions

Breast NeoplasmsOvarian NeoplasmsFanconi Anemia, Complementation Group D1

Interventions

Carboplatinolaparib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic Chemicals

Study Officials

  • Sabine Linn, MD, PhD

    The Netherlands Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 9, 2015

First Posted

April 16, 2015

Study Start

May 1, 2015

Primary Completion

January 1, 2019

Study Completion

January 1, 2019

Last Updated

January 16, 2019

Record last verified: 2019-01

Locations

NL(1)