Olaparib as Salvage Treatment for Cisplatin-resistant Germ Cell Tumor

• Status: Active, not recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This is open-label, single-arm, two-stage phase II trial of olaparib in patients with relapsed/refractory metastatic germ cell cancer. The primary objective is to evaluate the preliminary activity of Olaparib in GCT tumors. The secondary objective is to evaluate the safety of Olaparib in patients with cisplatin-refractory GCT.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Treatments: Cisplatin; Olaparib

Criteria

Inclusion criteria:

1. Patients ≥ 18 years old

2. Histologically verified metastatic gonadal GCT or extragonadal GCT originating from retroperitoneum or mediastinum.

3. Disease progression during cisplatin-based chemotherapy or disease progression or relapse after high-dose chemotherapy or disease progression or relapse after at least 2 different cisplatin-based regimens

4. patients who progressed during cisplatin-based therapy and who are not eligible for high-dose chemotherapy

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0-2

6. Life expectancy ≥3 months

7. At baseline adequate function of liver, kidneys and bone marrow

• Neutrophils ≥ 1500 /mm3;

• Hemoglobin ≥ 9.0 g/dL;

• Platelets ≥ 80 x109/L;

• Creatinine ≤ 1.5x upper limit of normal (ULN) In case of liver metastases increased levels of the following three parameters is acceptable:

• Bilirubin ≤ 1.5 x ULN

• serum glutamate oxaloacetate transaminase (SGOT (AST) ≤2.5 x ULN

• serum glutamate pyruvate transaminase (SGPT (ALT) < 2.5 x ULN;

8. Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to International Conference on Harmonization Good Clinical Practice (ICH GCP), and national/local regulations.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

9. At least one measurable lesion that can be accurately assessed by CT/MRI/plain x-ray) at baseline and follow up visits.

Exclusion criteria:

1. Systemic antitumor treatment within 21 days before study entry

2. Simultaneous radiotherapy to the only target lesion

3. Patients with resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ≤470 msec

4. Patients who have experienced a seizure or seizures within 6 months of study treatment or who are currently being treated with cytochrome P450 enzyme inducing anti-epileptic drugs for seizures.

5. Patients with uncontrolled brain metastases.

6. Patients receiving prohibited classes of inhibitors of CYP3A4 (see section 6.5.1).

7. Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.

8. Patients with any acute toxicities due to previous cancer treatment that have not resolved to a Common Toxicity Criteria for Adverse Effects (NCI-CTCAE v 4.03) grade 0 or 1 with the exception of chemotherapy induced alopecia and grade 2 peripheral neuropathy.

9. Patients affected by myelodysplastic syndrome or acute myeloid leukemia

10. Known to be serologically positive for HIV and receiving antiretroviral therapy

11. Known seropositive for active viral infection with hepatitis B virus (HBV) (patients who are HBsAg negative, anti-HBs positive and/or hepatitis B core antigen (Anti-HBc) positive, but viral DNA negative are eligible)

12. Known seropositive for active infection with hepatitis C virus (HCV)

13. Patients unwilling or unable to comply with the protocol

14. Patients with unstable angina pectoris, myocardial infarction ≤ 6 months prior to first study treatment, congestive heart failure New York Heart Association (NYHA) III-IV or serious uncontrolled cardiac arrhythmias

15. Patients with an active or uncontrolled infection

16. Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer

17. Patients who have undergone major surgery within 4 weeks prior to starting study drug (e.g. intra-thoracic, intra-abdominal, or intra-pelvic) or significant traumatic injury, or who have not recovered from the side effects of any of the above within 6 weeks

18. Patients who have participated in another interventional clinical trial within 30 days before study entry

19. Other serious medical conditions that could impair the ability of the patient to participate in the study

20. Active infection requiring systemic antibiotic-, anti-viral-, or anti-fungal medication

21. Active cancer (other than GCT) including prior malignancy from which the patient has been disease-free for ≤3 years (except superficial basal cell skin cancer)

22. Patients with a known hypersensitivity to the combination/comparator agent

23. Patients with uncontrolled seizures.