Olaparib as Salvage Treatment for Cisplatin-resistant Germ Cell Tumor

NCT02533765 | Completed Phase 2

• 1 other identifier: IRST186.02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Neoplasms, Germ Cell and Embryonal

Keywords

Cisplatin-resistant; Neoplasms, Germ Cell and Embryonal; Salvage treatment; olaparib

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The percentage of patients whose cancer achieve either a partial response or a complete response.Tumor response will be assessed using CT scan or MRI of chest/abdomen using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and by tumor marker (AFP, betaHCG, LDH) measurements

  Up to 30 months

Secondary Outcomes (4)

• Evaluation of number, type and grade of Adverse Events

  Up to 30 months

• Progression free survival (PFS)

  Up to 30 months

• Overall survival (OS)

  Up to 30 months

• exploratory analysis of the association between PFS or OS and biomarkers

  Up to 30 months

Study Arms (1)

Olaparib

EXPERIMENTAL

Olaparib 300mg twice daily continuously

Drug: Olaparib

Interventions

Olaparib DRUG

Olaparib dispensed to patients at the dose of 300 mg twice daily (BID) continuously until the patient completes the study, withdraws from the study or closure of the study.

Also known as: AZD2281

Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years old
• Histologically verified metastatic gonadal GCT or extragonadal GCT originating from retroperitoneum or mediastinum.
• 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
• patients who progressed during cisplatin-based therapy and who are not eligible for high-dose chemotherapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0-2
• Life expectancy ≥3 months
• 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;
• 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.

You may not qualify if:

• Systemic antitumor treatment within 21 days before study entry
• Simultaneous radiotherapy to the only target lesion
• 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
• 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.
• Patients with uncontrolled brain metastases.
• Patients receiving prohibited classes of inhibitors of CYP3A4 (see section 6.5.1).
• Patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• 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.
• Patients affected by myelodysplastic syndrome or acute myeloid leukemia
• Known to be serologically positive for HIV and receiving antiretroviral therapy
• 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)
• Known seropositive for active infection with hepatitis C virus (HCV)
• Patients unwilling or unable to comply with the protocol
• 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
• Patients with an active or uncontrolled infection

Sponsors & Collaborators

• Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS: lead

Study Sites (2)

U.O Oncologia Medica, IRST IRCCS

Meldola, FC, 47014, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G.Pascale"

Napoli, 80131, Italy

Location

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Study Officials

• Ugo De Giorgi, MD

  IRST IRCCS, Meldola

  PRINCIPAL INVESTIGATOR

• Sandro Pignata, MD

  Istituto Nazionale Tumori di Napoli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: August 27, 2015
• Study Start: September 11, 2015
• Primary Completion: September 1, 2018
• Study Completion: February 13, 2023
• Last Updated: January 30, 2025

Record last verified: 2025-01

Locations

IT (2)