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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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

Condition or disease Intervention/treatment Phase
Breast Cancer Ovarian Cancer Advanced Cancer Drug: carboplatin, olaparib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : May 2015
Actual Primary Completion Date : January 2019
Actual Study Completion Date : January 2019


Arm Intervention/treatment
Experimental: Dose escalation
carboplatin, olaparib
Drug: carboplatin, olaparib
2 cycles of carboplatin and olaparib combination therapy followed by olaparib monotherapy.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Pharmacokinetics (area under time-concentration curve (AUC)) [ Time Frame: 1 year ]
    Pharmacokinetics (PK) measurements of olaparib alone and olaparib in combination with carboplatin

  2. 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

  3. Objective Response Rate [ Time Frame: 1 year ]
    Objective Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02418624


Locations
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Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands, 1066CX
Sponsors and Collaborators
The Netherlands Cancer Institute
Investigators
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Principal Investigator: Sabine Linn, MD, PhD The Netherlands Cancer Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT02418624    
Other Study ID Numbers: M14REV
NL50610.031.14 ( Other Identifier: Netherlands CCMO )
2013-005590-41 ( EudraCT Number )
First Posted: April 16, 2015    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Keywords provided by The Netherlands Cancer Institute:
breast cancer 1, early onset (BRCA1)
breast cancer 2, early onset (BRCA2)
homologous recombination deficiency
carboplatin
olaparib
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Olaparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action