A Phase I Dose-escalation Study of Subcutaneous ALM201 in Patients With Advanced Ovarian Cancer and Other Solid Tumours

NCT03427073 | Terminated Phase 1 Results

• 1 other identifier: ALM201/0001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

ALM201/0001 is a Phase I, open-label, dose-escalation study of the safety, tolerability and pharmacokinetics (PK) of ALM201. Part 1 will be a dose-escalation study. Patients with advanced solid tumours will receive daily doses of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles. Part 2 will be a dose-expansion of the Maximum Tolerated Dose (MTD) determined in Part 1. Patients with advanced ovarian cancer will be enrolled with the main objective to determine the recommended Phase II dose.

Conditions

Solid Tumors; Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability - Evaluation of AEs and DLT

  All events and suspected dose limiting toxicities (DLTs) were graded according to the CTCAE, version 4.03. A DLT was defined as a Grade 3 or 4 AE that, in the opinion of the CRC, was likely to be related to ALM201 and represented a clinically significant hazard to the patient. Qualifying DLT events were considered to be clinically relevant; e.g. in duration, apparent reversibility, required management, and upon consideration of the patient's medical history and/or concomitant medications. DLT events were also evaluated in terms of what was considered to be an appropriate next escalation step: In the case where the CRC agreed that an escalation step of approximately 33% or lower was merited; the toxicity of concern could be declared a DLT. In order to be evaluable for DLT assessment, a patient had to receive at least 80% of their scheduled doses (e.g. 12 of the 15), unless this lack of compliance was due to ALM201-related toxicity.

  Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1

Secondary Outcomes (4)

• Tumour Response Assessment - Best Overall Response

  Response assessments were done to assess clinical benefit in the efficacy population overall and at the end of cycles 2, 4 and 6, as applicable

• Pharmacokinetics: Tmax

  Tmax was determined in cycles 1, 2, 4 and 6 of treatment

• Pharmacokinetics: AUC 0-t

  AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment

• Pharmacokinetics: Cmax

  Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment

Study Arms (2)

Solid tumours

EXPERIMENTAL

Part 1 - Dose-escalation of ALM201 in patients with advanced solid tumours Daily dosing of ALM201 on Days 1-5, 8-12 and 15-19 of 21 day cycle. Escalating dose cohorts

Drug: ALM201

Ovarian cancer

EXPERIMENTAL

Part 2 - Dose-expansion of ALM201 Maximum Tolerated Dose (MTD) in patients with advanced ovarian cancer Daily dosing of ALM201 on Days 1-5, 8-12 and 15-19 of 21 day cycle at the MTD determined in Part 1

Drug: ALM201

Interventions

ALM201 DRUG

Drug: ALM201 administered subcutaneously

Ovarian cancer; Solid tumours

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \*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
• \*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.
• Measurable or evaluable disease.
• Recovery from previous treatment to baseline or CTCAE ≤ Grade 1, as determined by CTCAE v4.03 criteria (Appendix B), 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 \< Grade 2 gastrointestinal toxicity; complete recovery from surgery other than stable \< Grade 2 toxicity.
• ECOG Performance Status (PS) of 0 or 1.
• Acceptable haematological, renal and hepatic
• Women must have either a negative pregnancy test prior to first study drug administration or be post menopausal. Male and female patients of childbearing potential must use appropriate methods birth control.
• Patients must give written informed consent and understand the requirements of the study

You may not qualify if:

• For all Patients
• History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events.
• Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography.
• Patents has received:
• 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.
• radiotherapy, immunotherapy or biological agents (includes investigational agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.
• Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours.
• Cancer with leptomeningeal involvement.
• On therapeutic anti-coagulation (aspirin dosing ≤100 mg per oral (PO) daily allowed).
• 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.
• Active cardiac condition or history of significant cardiac condition. Known human immunodeficiency virus positivity.
• Active hepatitis B or C or other active liver disease (other than malignancy).
• Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1.
• 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.

Sponsors & Collaborators

• Almac Discovery: lead

Study Sites (3)

Centre for Cancer Research and Cell Biology, Queen's University Belfast

Belfast, County Antrim, BT9 7AB, United Kingdom

Location

Dept Medical Oncology, The Christie NHS Foundation Trust

Manchester, Lancashire, M20 4BX, United Kingdom

Location

Freeman Hospital, Northern Centre for Cancer Care, Sir Bobby Robson Cancer Trial research Centre

Newcastle, Northumberland, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Limitations and Caveats

The study was terminated after Part 1 to re-evaluate the biomarker strategy for recruitment to Part 2

Results Point of Contact

• Title: Professor Richard Kennedy, Medical Director
• Organization: Almac Discovery

richard.kennedy@almacgroup.com

+44 28 3833 2200

Study Officials

• Richard Wilson, Professor

  Centre for Cancer Research and Cell Biology, Queen's University Belfast

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2015
• First Posted: February 9, 2018
• Study Start: April 27, 2015
• Primary Completion: March 13, 2017
• Study Completion: March 13, 2017
• Last Updated: September 11, 2019
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Locations

GB (3)