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Phase I of Carboplatin-Olaparib Followed by Olaparib Monotherapy in Advanced Cancer (REVIVAL)

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ClinicalTrials.gov Identifier: NCT02418624
Recruitment Status : Completed
First Posted : April 16, 2015
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Tracking Information
First Submitted Date  ICMJE March 9, 2015
First Posted Date  ICMJE April 16, 2015
Last Update Posted Date January 16, 2019
Study Start Date  ICMJE May 2015
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02418624 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2015)
  • Pharmacokinetics (area under time-concentration curve (AUC)) [ Time Frame: 1 year ]
    Pharmacokinetics (PK) measurements of olaparib alone and olaparib in combination with carboplatin
  • Pharmacodynamics (PAR (Poly(ADP) ribose) activation measured with the PAR assay) [ Time Frame: 1 year ]
    PAR (Poly(ADP) ribose) activation measured with the PAR assay
  • Objective Response Rate [ Time Frame: 1 year ]
    Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I of Carboplatin-Olaparib Followed by Olaparib Monotherapy in Advanced Cancer
Official Title  ICMJE 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
Brief Summary 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Ovarian Cancer
  • Advanced Cancer
Intervention  ICMJE Drug: carboplatin, olaparib
2 cycles of carboplatin and olaparib combination therapy followed by olaparib monotherapy.
Study Arms  ICMJE Experimental: Dose escalation
carboplatin, olaparib
Intervention: Drug: carboplatin, olaparib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 14, 2019)
25
Original Estimated Enrollment  ICMJE
 (submitted: April 13, 2015)
15
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. 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);
  2. Age ≥ 18 years;
  3. Able and willing to give written informed consent;
  4. WHO performance status of 0, 1 or 2;
  5. Able and willing to undergo blood sampling for PK and PD analysis;
  6. Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
  7. Evaluable disease according to RECIST 1.1 criteria;
  8. Minimal acceptable safety laboratory values

    1. ANC of ≥ 1.5 x 10^9 /L
    2. Hemoglobin of at least 6.2 mM and no transfusions in the last 28 days.
    3. Platelet count of ≥ 100 x 10^9 /L
    4. 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)
    5. Renal function as defined by serum creatinine ≤1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
  9. Negative pregnancy test (urine/serum) for female patients with childbearing potential;

Exclusion criteria

  1. 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;
  2. 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;
  3. 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
  4. Women who have a positive pregnancy test (urine/serum) and/or who are breast feeding;
  5. 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)
  6. 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;
  7. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
  8. Patients with known active hepatitis B or C;
  9. Recent myocardial infarction (< six months) or unstable angina;
  10. 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.
  11. Known leptomeningeal metastases.
  12. Patients with myelodysplastic syndrome or acute myeloid leukemia
  13. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02418624
Other Study ID Numbers  ICMJE M14REV
NL50610.031.14 ( Other Identifier: Netherlands CCMO )
2013-005590-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Netherlands Cancer Institute
Study Sponsor  ICMJE The Netherlands Cancer Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sabine Linn, MD, PhD The Netherlands Cancer Institute
PRS Account The Netherlands Cancer Institute
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP