A Phase I Trial of LY3143921 Hydrate in Solid Tumours

NCT03096054 | Completed Phase 1 DMC

• 3 other identifiers: CRUKD/17/0042016-001245-80ISRCTN84044406
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 4

Brief Summary

This clinical study looked at a drug called LY3143921 hydrate (a Cdc7 inhibitor) in adult patients with advanced solid tumours. The main aims were to find out the maximum dose of LY3143921 hydrate that could be given safely to patients, and to assess the potential side effects and how they could be treated.

Conditions

Squamous Carcinoma of the Head and Neck (Human Papillomavirus (HPV) Negative); Colorectal Cancer; High Grade Serous Ovarian Cancer; Non Small-cell Lung Cancer (Squamous Cell Variant); Urothelial Cancer; Breast Cancer (Triple Negative Type); Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Determination of the maximum tolerated dose (MTD)

  The maximal dose was determined as the dose at which no more than one patient out of up to six patients at the same dose level experienced a highly probable or probable drug-related dose-limiting toxicity (DLT), and the schedule of administration at which the maximum tolerated dose (MTD) was established was determined.

  28 days from first administration of LY3143921 hydrate in the dose escalation cohort, including the single dose on Cycle 1 Day -7.

• Determination of adverse event (AE) causality and grade

  The causality of each AE and grade to LY3143921 hydrate was determined according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.02.

  From first administration of LY3143921 hydrate until last patient's last visit (LPLV).

Secondary Outcomes (8)

• Determine the maximum observed plasma concentration (Cmax) of LY3143921

  Up to 10 time points per patient per visit.

• Determine the time to reach Cmax for LY3143921 (Tmax)

  Up to 10 time points per patient per visit.

• Determine under the plasma-concentration time curve for LY3143921

  Up to 10 time points per patient per visit.

• Determine the plasma half-life of LY3143921

  Up to 10 time points per patient per visit.

• Determine the volume of distribution for LY3143921

  Up to 10 time points per patient per visit.

Study Arms (2)

Part 1 a dose escalation

EXPERIMENTAL

Phase where groups of patients received increasing doses of LY3143921 hydrate to find a safe dose and a dose that best targeted the cancer cells.

Drug: LY3143921 hydrate

Part 2 an expansion

EXPERIMENTAL

Phase where a larger group of patients received the highest dose of LY3143921 hydrate considered to be safe from Part 1, to find out more about how the drug worked.

Drug: LY3143921 hydrate

Interventions

LY3143921 hydrate DRUG

LY3143921 hydrate was administered orally on a daily schedule. Each cycle of treatment consisted of 21 days, and patients may have initially received up to 12 cycles. If the patient was benefitting, they may have continued beyond 12 cycles.

Part 1 a dose escalation; Part 2 an expansion

Eligibility Criteria

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

You may qualify if:

• Histologically proven advanced or metastatic solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient.
• For Phase I Part 1 (dose escalation): Enriched for patients with tumours commonly associated with p53 mutation or loss of function:
• Colorectal cancer (CRC)
• High grade serous ovarian cancer
• Non small-cell lung cancer (NSCLC, squamous variant)
• Squamous carcinoma of the oesophagus
• Squamous carcinoma of the head and neck (HPV negative)
• Urothelial cancer
• Breast cancer (triple negative type)
• Pancreatic cancer
• For Phase I Part 2 (expansion cohorts): Cohort 1: patients with metastatic CRC; Cohort 2: patients with squamous NSCLC and Cohort 3: patients with solid tumours commonly associated with p53 mutation or loss of function (as described above for the Phase 1 Part 1 part of the trial).
• Consent for pre-treatment and post-treatment fresh tumour biopsy samples in a minimum of six patients in expansion Cohorts 1 and 3, optional for all other patients.
• Consent for pre and post treatment skin punch biopsy in a minimum of six patients in each dose expansion cohort; optional in all remaining patients.
• Life expectancy of at least 12 weeks.
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.

You may not qualify if:

• Systemic anti-cancer therapy (with the exception of life-long hormone suppression such as luteinising hormone-releasing hormone agents in prostate cancer) or another investigational agent during the previous 4 weeks (6 weeks for nitrosureas, Mitomycin-C) is not permitted. Previous use of radiotherapy is permitted except where there has been a large volume of bone marrow irradiated or where the irradiated lesion is the only one suitable for RECIST measurability.
• Ongoing toxic manifestations of previous treatments (Grade 2 or greater according to NCI-CTCAE version 4.02) with the exception of alopecia or certain Grade 2 toxicities, which in the opinion of the investigator and Sponsor should not exclude the patient - these should be discussed on a case by case basis.
• Symptomatic brain metastases or spinal cord compression.
• Significant baseline hypotension or symptomatic hypotension at any level of BP (\<90 mmgHg systolic or \<50 mmHg diastolic).
• Uncontrolled hypertension (\>160 mmHg/100 mmHg).
• Patients with a known left ventricular ejection fraction \<50%. An echocardiogram must be performed in all patients.
• Women of child-bearing potential (or who are already pregnant or lactating). However, those patients who meet the following points are considered eligible:
• Have a negative serum or urine pregnancy test before enrolment and;
• Agree to use two forms of contraception (one effective form plus a barrier method \[oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom\]) or agree to sexual abstinence, effective from the first administration of LY3143921 hydrate, throughout the trial and for 6 months afterwards.
• Male patients with partners of child-bearing potential. However, those patients who meet the following points are considered eligible:
• Agree to take measures not to father children by using a barrier method of contraception \[condom plus spermicide\] or to sexual abstinence effective from the first administration of LY3143921 hydrate, throughout the trial and for 6 months afterwards.
• Men with partners of child-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intra-uterine device, diaphragm with spermicidal gel or sexual abstinence.
• Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (mandatory testing not required).

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (4)

Northern Ireland Cancer Centre

Belfast, BT9 7JL, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Links

• ISRCTN: A Phase I trial of LY3143921 hydrate in solid tumours

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Pancreatic Neoplasms; Papillomavirus Infections

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 30, 2017
• Study Start: June 21, 2017
• Primary Completion: April 9, 2025
• Study Completion: April 9, 2025
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)