A Phase 1/2 Trial SRA737 in Combination With Gemcitabine and Cisplatin or Gemcitabine Alone in Advanced Cancer Subjects
A Phase 1/2 Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Alone in Subjects With Advanced Cancer
1 other identifier
interventional
153
2 countries
20
Brief Summary
The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose (RP2D) and schedule of SRA737 in combination with low dose gemcitabine; and to evaluate the efficacy of SRA737 in combination with low dose gemcitabine in prospectively-selected subjects with genetically-defined tumors that have predicted sensitivity to Chk1 inhibition based on factors including: genetic profiling of tumor tissue or ctDNA, HPV status, and germline BRCA1 and BRCA2 gene status. Specific cancer indications that frequently feature these factors will be studied. Preclinical and clinical data support the hypothesis that active doses of SRA737 may be strongly potentiated by sub-therapeutic doses of gemcitabine, which should lead to clinical efficacy. To test this hypothesis, SRA737 in combination with low dose gemcitabine is being explored in this study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2016
Typical duration for phase_1
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2016
CompletedFirst Posted
Study publicly available on registry
June 14, 2016
CompletedStudy Start
First participant enrolled
July 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 8, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2020
CompletedJune 22, 2023
June 1, 2022
3.8 years
May 23, 2016
June 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of subjects with adverse events as assessed by CTCAE4.03
Up to 30 days after last dose of SRA737
Maximum tolerated dose of SRA737 administered in combination with gemcitabine
Cycle 1 (28 days) in the Dose Escalation Phase
Recommended Phase 2 dose of SRA737 in combination with gemcitabine.
Up to 30 days after last dose of SRA737
Study Arms (2)
Standard-Dose Triplet Combination
EXPERIMENTALSRA737 will be administered orally on Days 2, 3, 9, and 10 of each 21-day cycle. Subjects will receive a single dose of SRA737 between 4 to 7 days prior to starting the first cycle for PK profiling. Gemcitabine will be administered intravenously on Days 1 and 8 of each 21-day cycle. Cisplatin will be administered on Day 1 of each 21-day cycle. Subjects can continue taking the study treatment if they are safely receiving clinical benefit and able to follow the requirements of the study.
Low-Dose Gemcitabine Combination
EXPERIMENTALSRA737 will be administered orally on Days 2, 3, 9, 10, 16, and 17 of each 28-day cycle. Subjects will receive a single dose of SRA737 between 4 to 7 days prior to starting the first cycle. Gemcitabine will be administered intravenously on Days 1, 8, and 15 of each 28-day cycle. Subjects can continue taking the study treatment if they are safely receiving clinical benefit and able to follow the requirements of the study.
Interventions
Eligibility Criteria
You may qualify if:
- For Dose Escalation: subjects with locally advanced or metastatic, histologically or cytologically proven solid tumor, relapsed after or progressing despite conventional treatment
- Life expectancy of at least 12 weeks
- World Health Organization (WHO) performance status of 0-1
- Must meet select hematological and biochemical laboratory indices
- Archival tumor tissue or accessible tumor and willingness to consent to a biopsy
- Expansion Only:
- Histologically or cytologically proven advanced malignancy of the following types, for which no other conventional therapy is considered appropriate:
- High-grade serous ovarian cancer (HGSOC)
- Small cell lung cancer
- Soft tissue sarcoma
- Cervical/anogenital cancer
- Measurable disease per RECIST v1.1
- Subjects must have predicted sensitivity to Chk1 inhibition based on factors including: genetic profiling of tumor tissue or ctDNA, HPV status, and germline BRCA1 and BRCA2 gene status. All subjects will have genetic profiling from tumor tissue or ctDNA; profiling will be performed prospectively if required to evaluate Chk1 sensitivity or otherwise performed retrospectively.
- For subjects with HGSOC, documented somatic or germline BRCA1 and BRCA2 wild-type status will confer eligibility without requirement for prospective genetic profiling. If documented BRCA status is not available, genetic profiling may be performed prospectively to determine eligibility.
- Subjects with SCLC are eligible without requirement for prospective genetic profiling on the basis of very high prevalence of cancer related alterations in the tumor suppressor genes (eg, TP53 and RB1) in this population.
- +6 more criteria
You may not qualify if:
- Received the following prior or current anticancer therapy in the timeframes noted prior to receiving SRA737 and have recovered from toxicity:
- Radiotherapy, chemotherapy, PARP inhibitors, other targeted therapies, or other IMPs within 2 weeks
- Nitrosoureas or Mitomycin C within 6 weeks
- Any prior treatment with a Chk1 inhibitor at any point or prior treatment with an ATR inhibitor within 6 months
- No more than 3 previous treatment regimens for advanced disease (not applicable to HGSOC expansion cohort)
- Other malignancy within the past 2 years, except for adequately treated tumors
- If, in the opinion of the Investigator, the subject is highly likely to experience clinically significant myelosuppression
- Ongoing toxic manifestations of previous treatments greater than NCI-CTCAE Grade 1
- History of allergy to gemcitabine
- New or progressing brain metastases. Subjects with brain metastases that have been asymptomatic and radiologically stable over an 8-week period and have not been treated with steroids during that time may be included with approval from the sponsor.
- High medical risk because of nonmalignant systemic disease
- Serologically positive for hepatitis B, hepatitis C or HIV
- Serious cardiac condition, left ventricular ejection fraction \< 45% at baseline, history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment, unless approved by the sponsor.
- Prior bone marrow transplant or extensive radiotherapy to greater than 25% of bone marrow within the previous 8 weeks
- Peanut allergy
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
START Madrid
Madrid, 28040, Spain
Hospital Universitario 12 de Octobre
Madrid, 28041, Spain
Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Biomedical Research Institute INCLIVA
Valencia, 46010, Spain
Royal Marsden Hospital
Sutton, London, SM2 5PT, United Kingdom
Belfast City Hospital
Belfast, Northern Ireland, BT9 7AB, United Kingdom
Oxford University Hospitals
Headington, Oxford, OX3 7LE, United Kingdom
Velindre Cancer Centre
Cardiff, Whitchurch, CF14 2TL, United Kingdom
The Clatterbridge Cancer Centre
Bebington, Wirral, CH63 4JY, United Kingdom
The Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Leeds Teaching Hospital of St James University Hospital
Leeds, LS9 7TF, United Kingdom
University Hospital of Leceister NHS TRUST
Leicester, LE1 5WW, United Kingdom
Guy's and St Thomas'
London, SE1 9RT, United Kingdom
Sarah Cannon Research Institute
London, W1G 6AD, United Kingdom
University College London
London, WC1E 6BT, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Sheffield Teaching Hospitals
Sheffield, S10 2SJ, United Kingdom
Related Publications (1)
Jones R, Plummer R, Moreno V, Carter L, Roda D, Garralda E, Kristeleit R, Sarker D, Arkenau T, Roxburgh P, Walter HS, Blagden S, Anthoney A, Klencke BJ, Kowalski MM, Banerji U. A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer. Clin Cancer Res. 2023 Jan 17;29(2):331-340. doi: 10.1158/1078-0432.CCR-22-2074.
PMID: 36378548DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Director
Sierra Oncology LLC - a GSK company
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 23, 2016
First Posted
June 14, 2016
Study Start
July 1, 2016
Primary Completion
April 8, 2020
Study Completion
April 8, 2020
Last Updated
June 22, 2023
Record last verified: 2022-06
Data Sharing
- IPD Sharing
- Will not share