olaparib + immunotherapy (durvalumab + tremelimumab) during 4 months followed by durvalumab alone as maintenance in patients with solid cancer and in response or stable after prior molecular target therapy by olaparib based on molecular sequencing.

Immunotherapy

STEP 1:
Olaparib 300 mg BID during 8 weeks. Olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food
STEP 2:
Olaparib 300 mg during 4 months as per same requirement as below. Durvalumab 1500 mg plus tremelimumab 75 mg via IV infusion Q4W, starting on Week 0, for up to a maximum of 4 doses followed by durvalumab monotherapy 1500 mg via IV infusion Q4W, starting 4 weeks after the last infusion of the combination and in response or stable after prior molecular target therapy by olaparib based on molecular sequencing.

olaparib, durvalumab, tremelimumab

CHU Amiens

CHRU Jean Minjoz

Institut Bergonié

CHU François Mitterrand

Institut Hospitalier Franco-Britannique

Centre Oscar Lambret

Centre Leon Berard

Study Evaluating the Efficacy of a Double Immunotherapy Combined With Olaparib in Patients With Solid Cancers and Carriers of Homologous Recombination Repair Genes After Olaparib Treatment

Precision Medicine Phase II Study Evaluating the Efficacy of a Double Immunotherapy by Durvalumab and Tremelimumab Combined With Olaparib in Patients With Solid Cancers and Carriers of Homologous Recombination Repair Genes Mutation in Response or Stable After Olaparib Treatment

Centre Georges Francois Leclerc

AstraZeneca

The therapeutic regimen will be divided into 2 different periods:
Radiotherapy period The patient will start IMRT (60Gy/30fr/6 weeks), TMZ(Temozolomide) chemotherapy (75mg/m²/day), and olaparib on the same day, on a Monday (day 1), within 6 weeks after surgery. The daily dose of TMZ (75 mg/m²) will be continued until the end of radiotherapy (6 weeks) and olaparib will be continued with the same dose until 4 weeks after the end of IMRT, as a single agent.
Maintenance period TMZ will then be re-introduced 4 weeks after the end of IMRT at the dose of 150 mg/m2/day on days 1 to 5 every 28 days, for a total of 6 cycles. Concomitantly, olaparib will be daily given at the maintenance dose level up to confirmed disease progression or unacceptable toxicities.
We propose 7 dose levels to reach the target dose of 400 mg per day (200 mg twice daily) of olaparib continuously

Malignant Gliomas

Radiotherapy

PARP Inhibitor

We propose 7 dose levels to reach the target dose of 400 mg per day (200 mg twice daily) of olaparib continuously DL1 (starting dose level) : Olaparib 50 mg Q12H Monday to wednesday DL2 : Olaparib 100mg Q12H Monday to wednesday DL3: Olaparib 100mg Q12H Monday to friday DL4 : Olaparib 200mg Q12H Monday to wednesday DL5: Olaparib 200mg Q12H Monday to friday DL6: Olaparib 200mg Q12H, continously

Olaparib

TMZ will be given at the dose of 75mg/m²/day during radiotherapy period. TMZ will be re-introduced 4 weeks after the end of radiotherapy at the dose of 150mg/m²/day on days 1 to 5 every 28 days, for a total of 6 cycles.

Temozolomide (TMZ)

Radiotherapy consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week over 6 weeks, for a total dose of 60 Gy by 3D- Intensity-Modulated RT (IMRT)

IMRT (Intensity Modulated Radiation Therapy)

Centre François Baclesse

Centre léon Bérard

Hôpitaux universitaires La Pitié Salpétrière - Charles Foix

Institut Curie

Institut Claudius Regaud

Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients

The primary objective for the phase I is to determine the Recommended Phase II Dose (RP2D) of olaparib combined with the Stupp protocol (TMZ and concomitant fractionated radiotherapy: 60Gy/30 fractions/6 weeks) in first line treatment of patients with unresectable high-grade gliomas

The primary objective for the phase II is to assess the 18-month overall survival of the combination

ribose/nekrose

Study Evaluating the Efficacy of a Double Immunotherapy Combined With Olaparib in Patients With Solid Cancers and Carriers of Homologous Recombination Repair Genes After Olaparib Treatment

Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients

Die vollständigste Datenbank für Heilkräuter, die von der Wissenschaft unterstützt wird