Weekly liposomal doxorubicin and cisplatin chemotherapy for patients with ovarian cancer, phase I study

JRCT ID: jRCTs031200007

Registered date:10/04/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: ovarian cancer
• Date of first enrollment: 03/06/2020
• Target sample size: 24
• Study type: Interventional
• Intervention(s): The starting dose of level 0 (PLD 7.5 mg/m2, CDDP 15 mg/m2), was chosen from 1/4 dose of PLD 30 mg/m2, CALYPSO study and 1/3 dose of CDDP 45 mg/m2/3weeks). At least three patients were treated at each dose level. Dose escalation to PLD; 10 (level 1), 12,5 (level 2), 15 mg/m2 (level 3), CDDP 20 (level 2), 25 mg/m2 (level 3, 4) was performed in accordance with a modified Fibonacci scale. Three additional patients were entered at the same dose level if DLT was observed in one of the first three patients. The MTD was defined as the dose level at which two patients out of three to six patients experienced DLT. DLT was defined as (a) >= grade 3 non-hematologic toxicity, (b) grade 4 thrombocytopenia, (c) grade 4 grannulocytopenia lasting for more than seven days, or (d) Febrile neutropenia. We evaluate the safety in two cycle in each patients at each level.The final determination of MTD or further dose escalation was made by a monitoring committee consisting of three independent members.

Outcome(s)

• Primary Outcome: Frequency of dose limiting toxicity at each level

Secondary Outcome

Progresssion-free survival
Effect of chemotherapy
Overall survival
Other adverse effects

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 79age old
• Gender: Female

Include criteria

(1) Ptients with histologically proven ovarian cancer who has received paclitaxel and carboplatin combination therapy in thier previous therapy.
(2) Ptients who could not receive paclitaxel and carboplatin combination therapy because of their adverse effects (carboplatin hypersensitivity reaction <= grade 2 or paclitaxel neurotoxicity>= grade3 )..
(3) Age 20-79 year
(4) Patient has a duration of 2 weeks or more from the end of the previous treatment.
(5) Patient had Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 and had be expected to alive more than three months.
(6) Adequate bone marrow function ( WBCs >=2,000/mm3, Neutrophil >=1,500/mm3, platelets >= 100,000/mm3), hepatic function (AST(GOT)=< 90 U/I, ALT(GPT)63 U/l =< 63 U/l ) and renal function ( serum creatinine =< 1.0 mg/dl, urea nitrogen =< 25 mg/dl), total bilirubin =< 1.0 mg/dl , Electrocardiogram; normal or slight change in normal range
(7) Patients gave informed written consent.
(8) Patients without hypersensivity reaction of liposomal doxorubicin and cisplatin

Exclude criteria

(1) New York Heart Association (NYHA) Class II or greater congestive heart failure, or serious arrhythmias requiring medication for treatment.
(2) Known history of hypersensitivity to paclitaxeal and carboplatin (grade >=3)
(3) Known history of myocardial infarction within 6 months prior to the enrollment.
(4) Patients with liver cirrhosis or interstitial pneumonia
(5) Patients with gastrointestinal fresh bleeding required with blood transfusion repeatedly
(6) Patients with psychic disturbance required with the treatment or in the treatment with an antipsychotic drug
(7) Patients with uncontrolled diabetes
(8) History of bowel obstruction, including sub-occlusive disease
(9) Multiple primary cancers.
(10) Patients who are inappropriate to enter this study with any safety reasons,judged by the treating physician.

Related Information

• Primary Sponsor: Tate Shinichi