Advanced ovarian cancer and other solid tumours MedDRA version: 17.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104
Conditions
Interventions
Product Code: ALM201
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALM201
Current Sponsor code: ALM201
Concentration
Sponsors
Almac Discovery
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (i) Part 1 Specific Inclusion Criterion: 1.Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available or felt likely to be of limited efficacy and in whom a rationale for use of an anti-angiogenic treatment approach exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated. (ii) Part 2 Specific Inclusion Criterion: 2.Patients with advanced ovarian cancer, who are intolerant of or whose tumour is resistant to platinums and who have failed to respond to, or have relapsed following, standard therapy and whose tumour has a proangiogenic profile as assessed by the angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is allowed if tolerated. (iii) General Inclusion Criteria for all Patients 3.Adult patients defined by age =16 years at time of consent. 4.Evaluable disease, either measurable on imaging, or with informative tumour marker(s), as assessed by RECIST 1.1 or other relevant response assessment criteria for tumour type. 5.Recovery from previous treatment to baseline or CTCAE = Grade 1, as determined by CTCAE v4.03 criteria of reversible toxicities related to prior treatment, with the exception of alopecia, lymphopenia, other non-clinically significant adverse events; recovery from previous radiotherapy other than residual cutaneous effects or stable 50 mL/min based on the Cockcroft-Gault formula; •Normal coagulation (elevated INR, prothrombin time or APTT = 1.3 x ULN range acceptable); •Urine protein =2+ (as measured by dipstick). 8.Negative urine or blood human chorionic gonadotropin (hCG) test during Screening and within 7 days of Cycle 1, Day 1 in women of childbearing potential (defined as women = 50 years of age or history of amenorrhea for = 12 months prior to study entry). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices, during the entire duration of the study and for 6 months after final administration of ALM201. Note that sterility in female patients must be confirmed in the patients’ medical records and can be defined as any of the following: surgical hysterectomy with bilateral
Exclusion criteria
Exclusion criteria: 1.History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events. 2.Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography. 3.Patents has received: a) any chemotherapy regimens (including investigational agents) with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle 1, Day 1, or received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of Cycle 1, Day 1. b) radiotherapy, immunotherapy or biological agents (includes investigational agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control. 4.Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours. 5.Cancer with leptomeningeal involvement. 6.On therapeutic anti-coagulation (aspirin dosing =100 mg per oral (PO) daily allowed). 7.Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumour was treated with curative intent more than 2 years prior to study entry. 8.History of clinically significant cardiac condition, including uncontrolled hypertension (BP >140/90 mmHg, despite medical therapy); left ventricular systolic dysfunction (ejection fraction (450 ms on screening 12-lead ECG); clinically significant cardiac arrhythmia within 3 months of study entry. Note: ventricular tachycardia, ventricular fibrillation, supraventricular tachycardia, atrial fibrillation without adequate heart rate control, atrial fibrillation with adequate heart rate control with or without medication or other treatment, are not an exclusion. 9.Known human immunodeficiency virus positivity. 10.Active hepatitis B or C or other active liver disease (other than malignancy). 11.Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1. 12.Any evidence of severe or uncontrolled systemic conditions or any other issues which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to characterise the safety and tolerability of ALM201 (Part 1 and Part 2) and to identify a recommended phase 2 dose (RP2D) and schedule of ALM201 (Part 2 only); Secondary Objective: The secondary objectives are: •To establish the pharmacokinetic profile of ALM201 •To assess anti-tumour activity •To assess anti-tumour activity in a biomarker-enriched group of patients with advanced ovarian cancer (Part 2 only) ; Primary end point(s): •Ongoing evaluation of AEs during treatment and follow up; evaluation of DLT during Cycle 1 (Part 1 only) •Safety, PK, PD and tumour response assessments for identification of RP2D ; Timepoint(s) of evaluation of this end point: Adverse events will be noted at every clinical visit & recorded at least every week. Evaluation of DLT ongoing throughout Part 1. Safety assessed throughout study. A PK profile for ALM201 will be taken on Days 1, 3 & 18 of Cycle 1 & on Day 18 of Cycles 2, 4, 6 & 8. Pre-dose samples will also be taken on Cycles 2-8 on Day 1. Biopsies for biomarker/PD evaluation will be taken at Screening & up to 2 post-treatment. Up to 12 post-treatment biomarker/PD samples in blood and 2 post-treatment biomarker/PD samples in ascites will be taken. Tumour assessment by imaging, or informative markers where relevant, will be assessed at Screening & after every 2 cycles of treatment during Cycles 1–8 & then after every 4 cycles, & may be performed at other times as clinically indicated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Assessment of pharmacokinetic variables (including Cmax, Cmin, AUC) •Tumour response assessment by RECIST 1.1 and/or other relevant response assessments for tumour types enrolled ; Timepoint(s) of evaluation of this end point: Patients will have a 12-hour urine collection on Cycle 1, Day 1 for urine PK analysis. Patients will have PK blood sampling conducted at Cycle 1, Day 1; Cycle 1, Day 3 & 18; Cycles 2, 4, 6 & 8, Day 18. A single pre-dose sample will also be taken on Cycles 2-8, on Day 1. Tumour assessment will follow RECIST 1.1 after every 2 cycles. | — |
Countries
United Kingdom
Contacts
Public ContactALM201/0001 Project Manager
Ockham Europe Ltd
Outcome results
None listed