A Phase 1/2 Trial of SRA737 in Combination with Gemcitabine plus Cisplatin or Gemcitabine Alone in Subjects with Advanced Cancer
- Conditions
- Histologically or cytologically proven solid tumours where treatment with gemcitabine plus cisplatin or gemcitabine alone is considered appropriate by the Investigator.MedDRA version: 20.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004467-36-ES
- Lead Sponsor
- Sierra Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 140
Dose-Escalation and Cohort Expansion:
1) Written (signed and dated) informed consent and be capable of co-operating with treatment and follow up.
2) In the Dose Escalation Phase, subjects with a locally advanced or metastatic, histologically or cytologically proven solid tumor, relapsed after or progressing despite conventional treatment for which no conventional therapy is considered appropriate by the Investigator or is declined by the subject.
3) Life expectancy of at least 12 weeks.
4) World Health Organization (WHO) performance status of 0-1.
5) Hematological and biochemical indices within the ranges shown below, measured within 1 week prior to the subject receiving their first dose of IMP.
Hemoglobin - = 90 g/L
Absolute neutrophil count - = 1.5 × 10^9/L
Platelet count - = 100 × 10^9/L
Bilirubin - = 1.5 × upper limit of normal (ULN) unless due to Gilbert’s syndrome in which case up to 3 × ULN is permissible
Alanine aminotransferase and/or aspartate aminotransferase and Alkaline Phosphatase - = 2.5 × ULN unless raised due to tumor in which case up to 5 × ULN is permissible
Serum Creatinine - = 1.5 × ULN
6) Subjects who are 18 years or older at the time consent is given.
7) Subjects must have archival tumor tissue available for tumor profiling OR accessible tumor and willingness to consent to a biopsy for the collection of tumor tissue.
Cohort Expansion:
8) Subjects in the indication specific cohort expansion must have histologically or cytologically proven advanced malignancy of the types specified in Inclusion Criterion 11, for which no conventional therapy is considered appropriate by the Investigator or is declined by the subject.
9) Have measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria.
10) Have tumor tissue or ctDNA evidence that their tumor harbors one or more mutations that are expected to confer sensitivity to Chk1 inhibition. Eligibility will be determined by the sponsor’s review of genetic abnormalities detected in genes in the following categories, as detailed in Appendix 6:
a) Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RB1, TP53, etc. For relevant cancers, positive human papilloma virus (HPV) status is also considered for eligibility.
b) The DNA damage response pathway including ATM, BRCA1, BRCA2, mismatch repair genetic alterations and/or high microsatellite instability.
c) Genetic indicators of replicative stress such as gain of function/amplification of Chk1 or ATR or other related gene.
d) Oncogenic drivers such as MYC, KRAS, etc.
11) Subjects must meet one of the following criteria:
a) Urothelial Carcinoma
i) Histologically confirmed locally advanced and unresectable or metastatic urothelial carcinoma of the bladder, upper urinary tract or urethra
ii) Must have received at least 1 but no more than 3 prior regimens for advanced disease
b) Small Cell Lung Cancer
i) Must have received at least 1 but no more than 3 prior regimens for advanced disease
c) Soft Tissue Sarcoma
i) Including undifferentiated pleiomorphic sarcoma / malignant fibrous histiocytoma (MFH) (including high-grade spindle cell sarcoma / pleomorphic liposarcomas), leiomyosarcoma, and dedifferentiated liposarcomas.
ii) Must have received at least 1 but no more than 3 prior regimens for advanced disease
d) Cervical/Anogenital Cancer
i) Including all cervical carcinoma and advanced/metastatic squamous cell carcinoma of the anus, penis
1) Have received the following prior or current anticancer therapy:
a) Radiotherapy within 6 weeks prior to receiving first dose of SRA737 (except for symptom control and where the lesions will not be used as measurable disease),
b) Endocrine therapy during the 4 weeks prior to receiving SRA737 except for luteinizing hormone releasing hormone agonists for prostate cancer,
c) Chemotherapy during the 4 weeks prior to receiving SRA737,
d) Immunotherapy during the 6 weeks prior to receiving SRA737,
e) Nitrosoureas or Mitomycin C during the 6 weeks prior to receiving SRA737,
f) Other IMPs during the 4 weeks prior to SRA737 treatment, or
g) Prior treatment with a Chk1 at any point or ATR inhibitor within 6 months prior to receiving SRA737.
2) No more than 3 previous lines of cytotoxic chemotherapy for metastatic disease.
3) Other malignancies within the past 2 years with the exception of adequately treated tumors that are associated with an expected 5 year disease-free survival of = 95%.
4) If, in the opinion of the Investigator, the subject is highly likely to experience clinically significant myelosuppression, based on previous experience with chemotherapy.
5) Ongoing toxic manifestations of previous treatments greater than National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 1. Exceptions to this are alopecia or certain toxicities, which in the opinion of the Investigator and the sponsor’s Medical Monitor should not exclude the subject.
6) History of allergy to gemcitabine.
7) 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 steriods during that time may be included with approval from the sponsor.
8) Women of childbearing potential (WOCBP) or women who are already pregnant or lactating. However, those subjects who have a negative serum or urine pregnancy test before enrollment and agree to use 2 forms of contraception or agree to sexual abstinence, effective from the first administration of SRA737, throughout the trial and for 6 months afterwards are considered eligible.
9) Male subjects with partners of child bearing potential, unless they agree to take measures not to father children by using a barrier method of contraception defined, effective from the first administration of SRA737 through the trial and for 6 months after their final SRA737 dose. Men with pregnant or lactating partners must be advised to use barrier method contraception (eg, condom plus spermicidal gel) to prevent exposure of the fetus or neonate.
10) Major surgery from which the subject has not yet recovered.
11) At high medical risk because of nonmalignant systemic disease including active uncontrolled infection.
12) Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus.
13) Serious cardiac condition, such as concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), left ventricular ejection fraction < 45% at baseline, history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment.
14) Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within the previous 8 weeks.
15) Peanut allergy (unless this restriction is removed by the sponsor).
16) QTcF > 450 msec in adult males and >
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method