A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

Sponsor

Esperas Pharma Inc. (Other)

Overall Status

Completed

CT.gov ID

NCT02632448

Collaborator

(none)

119

Enrollment

Locations

Arms

67.9

Actual Duration (Months)

13.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
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	Drug: LY2880070 Drug: Gemcitabine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

119 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase 1b/2a Two-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

Actual Study Start Date :

May 16, 2016

Actual Primary Completion Date :

Jan 11, 2022

Actual Study Completion Date :

Jan 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: LY2880070 Multiple oral doses of LY2880070 during 21-day cycles	Drug: LY2880070 Capsules
Experimental: Part A: LY2880070 with Gemcitabine Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part A: LY2880070 (Metabolism Phenotype) Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers	Drug: LY2880070 Capsules
Experimental: Part B: LY2880070 and Gemcitabine (Breast) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Colorectal) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part B:LY2880070 and Gemcitabine (Ovarian) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Endometrial) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS)) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar
Experimental: Part B: LY2880070 and Gemcitabine (Pancreatic) Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)	Drug: LY2880070 Capsules Drug: Gemcitabine 50 to 600 milligrams per square meter of body surface area (mg/m2) Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose(s) [Baseline through Cycle 1 (Estimated up to 21 days)]

Secondary Outcome Measures

Number of dose limiting toxicities (DLTs) [Baseline through Cycle 1 (Estimated up to 21 days)]
Area under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-24) [Baseline to 24-hours post dose (up to Day 20 in Cycle 1)]
Peak plasma concentration (Cmax) [Baseline to 24 hours post-dose (up to Day 20 in Cycle 1)]
Time to reach maximum plasma concentration (tmax) [Baseline to 24 hours post dose (up to Day 20 in Cycle 1)]
Change from baseline in white blood cell count [Baseline to 24 hours post dose (up to Day 20 in Cycle 1)]
Change from baseline in neutrophil count [Baseline to 24 hours post dose (up to Day 20 in Cycle 1)]
Change from baseline in lymphocyte count [Baseline to 24 hours post dose (up to Day 20 in Cycle 1)]
Number of participants with tumor response (objective response rate) as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1) [Baseline to study completion (estimated up to 4 years)]
Duration of objective response [Baseline to study completion (estimated up to 4 years)]
Best response [Baseline to study completion (estimated up to 4 years)]
Progression free survival [Baseline to study completion (estimated up to 4 years)]
Overall survival [Baseline up to 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
2	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
4	Juravinski Cancer Center	Hamilton	Ontario	Canada	L8V 5C2
5	Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
6	University Health Network - Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
7	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
8	McGill University Health Centre	Montreal	Quebec	Canada	H4A 3J1
9	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec	Canada	H2X 0A9