A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

Phase 1

Recruiting

• Conditions: Ovarian Cancer; Endometrial Cancer; Soft Tissue Sarcoma; Triple Negative Breast Cancer; Pancreas Cancer; Solid Tumors; Colorectal Cancer; Neoplasms; Breast Cancer; Colon Cancer
• Interventions: Drug: LY2880070; Drug: Gemcitabine

• Registration Number: NCT02632448
• Lead Sponsor: Esperas Pharma Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-12-14
• Study First Submitted QC: 2015-12-15
• Study First Posted: 2015-12-16
• Study Start: 2016-05-16
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-27
• Last Update Posted: 2024-03-29
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 229

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part B: LY2880070 and Gemcitabine (Breast)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B:LY2880070 and Gemcitabine (Ovarian)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Colorectal)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part A: LY2880070	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles
Part A: LY2880070 (Metabolism Phenotype)	LY2880070	Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers
Part A: LY2880070 with Gemcitabine	LY2880070	Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles
Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Endometrial)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Pancreatic)	LY2880070	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part A: LY2880070 with Gemcitabine	Gemcitabine	Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles
Part B: LY2880070 and Gemcitabine (Colorectal)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Breast)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B:LY2880070 and Gemcitabine (Ovarian)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Endometrial)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part B: LY2880070 and Gemcitabine (Pancreatic)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)
Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)	Gemcitabine	Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously)

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose(s)	Baseline through Cycle 1 (Estimated up to 21 days)

Secondary Outcome Measures

Name	Time	Method
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)
Duration of objective response	Baseline to study completion (estimated up to 4 years)
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)
Overall survival	Baseline up to 1 year
Number of dose limiting toxicities (DLTs)	Baseline through Cycle 1 (Estimated up to 21 days)
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)
Best response	Baseline to study completion (estimated up to 4 years)
Progression free survival	Baseline to study completion (estimated up to 4 years)
Change from baseline in lymphocyte count	Baseline to 24 hours post dose (up to Day 20 in Cycle 1)

Trial Locations

Locations (16)

University Health Network - Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

BC Cancer Agency; 🇨🇦 Vancouver, British Columbia, Canada

McGill University Health Centre; 🇨🇦 Montreal, Quebec, Canada

University Hospital Centre Zagreb; 🇭🇷 Zagreb, Croatia

Centrum Onkologii im. prof. F. Łukaszczyka; 🇵🇱 Bydgoszcz, Poland

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada

Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz; 🇵🇱 Gdańsk, Poland

Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o. o.; 🇵🇱 Kraków, Poland

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada

Ottawa Hospital Cancer Centre; 🇨🇦 Ottawa, Ontario, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

General Hospital Zadar; 🇭🇷 Zadar, Croatia

Szpital Specjalistyczny im. L. Rydygiera w Krakowie sp. z o. o.; 🇵🇱 Kraków, Poland