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

NCT ID: NCT02418624

Last Updated: 2019-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2019-01-31

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.

Conditions

Breast Cancer; Ovarian Cancer; Advanced Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

carboplatin, olaparib

Group Type: EXPERIMENTAL

carboplatin, olaparib

Intervention Type: DRUG

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

Interventions

carboplatin, olaparib

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

Intervention Type: DRUG

Eligibility 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;

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sabine Linn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Netherlands Cancer Institute

Locations

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 27323902 (View on PubMed)

Other Identifiers

NL50610.031.14

Identifier Type: OTHER

Identifier Source: secondary_id

2013-005590-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14REV

Identifier Type: -

Identifier Source: org_study_id