Clinical trial NCT02632448: A Study of LY2880070 in Participants With Advanced or Metastatic Cancer
Official title: A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Colorectal Cancer
Breast Cancer
Ovarian Cancer
Colon Cancer
Rectal Cancer
Neoplasms
Endometrial Cancer
Soft Tissue Sarcoma
Triple Negative Breast Cancer
Pancreas Cancer
Pancreatic Cancer
Keywords: Metastatic cancer
Advanced cancer
Recurrent cancer
Colorectal neoplasms
Triple negative breast cancer
Ovarian neoplasms
Colon neoplasms
Rectal neoplasms
Triple negative breast neoplasms
Gastrointestinal stromal tumor
Pancreatic Neoplasms
Pancreatic Cancer
Lead sponsor: Esperas Pharma Inc.
Sponsor class: OTHER
First posted: 2015-12-16
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this 3-part study is to evaluate the safety and efficacy of the study drug known as LY2880070 in participants with advanced or metastatic solid tumors.


Eligibility criteria: Inclusion Criteria:

* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Have an estimated life expectancy of greater than or equal to (≥)12 weeks
* Have adequate organ function
* Have received 1-4 prior systemic therapies for locally advanced or metastatic disease
* Agree to use medically approved contraceptives during the study and for 3 months following the last study treatment
* All females must have a negative serum pregnancy test result, and females of child-bearing potential must have a negative urine pregnancy test result, prior to the first study treatment
* Have tumor lesions considered measurable by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Must be, in the judgment of the investigator, an appropriate candidate for experimental therapy, and no standard therapy would confer clinical benefit

For Part A

* Must have evidence of cancer (solid tumors, excluding glioblastoma and primary brain tumor) that is advanced or metastatic
* For the Metabolism Phenotype Arm in Part A, participants must have a Cytochrome P450 (CYP2D6) poor metabolizer phenotype

For Part B

* Have advanced or metastatic colorectal cancer, triple negative breast cancer (per American Society of Clinical Oncology-College of American Pathology guidelines), epithelial ovarian cancer, endometrial, soft tissue sarcoma, pancreatic cancer

  * For TNBC:

    * Recurrent/refractory Triple Negative Breast Cancer (TNBC) defined as any beast cancer that expresses \<1% estrogen receptor (ER) and \<1% progesterone receptor (PR) and is Her2 negative
  * For Colorectal (CRC):

    * Must have histologically confirmed advanced or metastatic colorectal cancer
  * For Ovarian Cancer:

    * Must have histologically confirmed advanced or metastatic epithelial ovarian cancer
    * Must be eligible to receive Gemzar (GEM) and not refractory to GEM/carboplatin
    * Must have the ability to tolerate GEM
    * May have received GEM as previous therapy
  * For Endometrial cancer:

    * Must have histologically confirmed endometrial cancer that is metastatic or locally advanced
    * Must have failed at least 1 prior chemotherapy
  * For STS:

    * Must have histologically confirmed STS that is metastatic or locally advanced
    * Patients with gastrointestinal stromal tumors (GIST) must have failed a KIT inhibitor
    * Must have failed at least 1 prior chemotherapy
  * For Pancreatic Cancer:

    * Must have histologically confirmed pancreatic cancer that is metastatic or locally advanced
    * Must have failed at least 1 prior chemotherapy regimen
  * For Part C
  * Participants with high grade serous ovarian cancer (HGSOC) will be screened for specific genetic signatures

Exclusion Criteria:

* Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment
* Have symptomatic central nervous system (CNS) metastasis
* Females who are pregnant or nursing
* Have known positive test results of human immunodeficiency virus, or have chronic active hepatitis A, B or C
* Have a corrected QT interval (QTcB) greater than (\>) 470 milliseconds (msec) (female) or \>450 msec (male), or a history of congenital long QT syndrome
* Have had a bone marrow transplant
* Have participated in this study, or are currently enrolled in another clinical study of an investigational medicinal product
* Have had radiation therapy to \>25% of bone marrow
* For Part B

  * Have a history of another active cancer within the past year, except cervical cancer in situ, in situ carcinoma of the bladder, basal cell carcinoma of the skin, or another in situ carcinoma that is considered cured

Primary outcomes:
measure: Maximum Tolerated Dose(s)
timeFrame: Baseline through Cycle 1 (Estimated up to 21 days)
Secondary outcomes:
measure: Number of dose limiting toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (Estimated up to 21 days)
measure: Area under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-24)
timeFrame: Baseline to 24-hours post dose (up to Day 20 in Cycle 1)
measure: Peak plasma concentration (Cmax)
timeFrame: Baseline to 24 hours post-dose (up to Day 20 in Cycle 1)
measure: Time to reach maximum plasma concentration (tmax)
timeFrame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
measure: Change from baseline in white blood cell count
timeFrame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
measure: Change from baseline in neutrophil count
timeFrame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
measure: Change from baseline in lymphocyte count
timeFrame: Baseline to 24 hours post dose (up to Day 20 in Cycle 1)
measure: Number of participants with tumor response (objective response rate) as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1)
timeFrame: Baseline to study completion (estimated up to 4 years)
measure: Duration of objective response
timeFrame: Baseline to study completion (estimated up to 4 years)
measure: Best response
timeFrame: Baseline to study completion (estimated up to 4 years)
measure: Progression free survival
timeFrame: Baseline to study completion (estimated up to 4 years)
measure: Overall survival
timeFrame: Baseline up to 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
city: Zadar
country: Croatia
facility: General Hospital Zadar
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. F. Łukaszczyka
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
city: Kraków
country: Poland
facility: Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o. o.
city: Kraków
country: Poland
facility: Szpital Specjalistyczny im. L. Rydygiera w Krakowie sp. z o. o.
Study officials:
affiliation: Esperas Pharma Inc.
name: Email: Darcy.Vincett@ozmosisresearch.ca
role: STUDY_DIRECTOR
References:
citation: W.H. Miller, A.F. Shields, D. Provencher, L. Gilbert, G. Shapiro, A.M. Oza, J. Spratlin, S. Lheureux, G. Bhat, S. Salvador, P. Nunes, S. Lau, I. Weiner, J. Keene, S. Zaknoen, P. Smith, J. Stille, D. Vincett, Q.S-C. Chu, 537P A phase I/II study of oral chk1 inhibitor LY2880070 in combination with low-dose gemcitabine in patients with advanced or metastatic ovarian cancer, Annals of Oncology, Volume 33, Supplement 7, 2022, Pages S793-S794, ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2022.07.665. (https://www.sciencedirect.com/science/article/pii/S0923753422025169)
citation: DOI: 10.1200/JCO.2020.38.15_suppl.3579 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3579-3579.
citation: DOI: 10.1200/JCO.2020.38.15_suppl.3581 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.