Metastatic or recurrent cervical cancer
Conditions
Interventions
Product Name: Combretastatin
Product Code: CA4P
Pharmaceutical Form: Powder for infusion*
Current Sponsor code: CA4P
Other descriptive name: Combretastatin
Concentration unit: mg/m2 milligram(s)/squar
Sponsors
Nordic Society for Gynecological Cancer
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Primary advanced (stage IVB), persistent or recurrent cancer of the uterine cervix considered incurable by surgery, radiotherapy and or chemotherapy. b) Histological verified squamous carcinoma, adenocarcinoma or adeno-squamous carcinoma c) Performance status (WHO) 0 or 1. d) Life expectancy > 12 weeks. e) Age > 18 years and 450 msec. or other clinically significant abnormalities. l) Sufficient kidney function with calculated (Cockroft-Gault) GFR > 50 ml/min and no uncontrolled hypokalemia and/or hypomagnesemia. m) Acceptable liver function with bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a) No combination of protocol treatment with attempts of curative surgery or radiotherapy. b) No previous inclusion in the protocol. c) No other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin. d) No CNS metastases. e) No major surgery within 4 weeks. f) No concomitant administration of other antineoplastic agents. g) No palliative radiotherapy unless at least one measurable lesion is left unirradiated. h) No history of angina (stable or more severe, even if controlled with medications), myocardial infarction, chronic heart failure, non-controlled atrial arrhythmias or clinically significant arrhythmias including conduction abnormality, nodal junctional arrhythmias and dysrhythmias, sinus bradycardia or tachycardia, supraventricular arrhythmias, atrial fibrillation or flutter, syncope or vasovagal episodes. i) Patients taking any drug(s) known to prolong the QTc interval, which cannot be interrupted for at least four days during each 7-day treatment cycle or patients with conditions associated with QTc prolongation cannot be included j) No uncontrolled hypertension (defined as blood pressure consistently greater than 150/100 mmHg irrespective of medication). k) No symptomatic peripheral vascular disease or cerebrovascular disease. l) No grade 2 (CTC v.3.0) or greater pre-existing peripheral neuropathy (motor or sensory); m) No psychiatric disorders or other conditions rendering patients incapable of complying with the requirements of the protocol. n) No active infection or other severe medical condition endangering treatment delivery. o) Patients, for whom regular follow-up attendance is impractical, are not eligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine toxicity, antitumor efficacy and outcome of weekly Cisplatin combined with the antivascular targeting agent Combretastatin in patients with advanced or recurrent cervical cancer considered incurable by standard treatment.;Primary end point(s): Phase I As toxicity is the primary endpoint a treatment free interval of at least 2 month from previous chemotherapy, radiotherapy or radio-chemotherapy is required to ensure that toxicity from previous treatment does not interfere with toxicity induced by Cisplatin and Combretastatin. Successive cohorts of 6 patients will be included in the trial at each dose level. The patients will be replaced, if they go off study before having received the first complete cycle (3 weekly infusions) of chemotherapy for any reason except toxicity. The time window for registration of dose limiting toxicity (DLT) is the first cycle of treatment (3 weekly infusions). Each cohort will be observed for a total of 6 weeks before a new dose level can be opened. However, any new toxicity encountered during subsequent treatment cycles should not be regarded as DLT. Three dose levels will be investigated. If 1 of 3 patients at a given dose level encounters dose limiting toxicity (DLT) the study proceeds at the same dose level for a total of 6 patients. As soon as more than 2 patients encounters DLT this dose level is declared as maximally tolerated dose (MTD). The dose level immediately below MTD will be declared as the recommended Phase 2 dose (RP2D). Additional dose levels with increments of 9 mg/m2 (free acid dose) of Combretastatin per dose level may be opened if MTD is not reached at the initial three dose levels. Phase-II Phase II involves an open labeled, stratified and one-to-one randomization between every third week Cisplatin 75 mg/m2 and weekly Cisplatin 40 mg/m2 combined with Combretastatin given at the RP2D dose level. As tumor growth delay rather than tumor regression is anticipated with Combretastatin, th | — |
Countries
Denmark
Outcome results
None listed