A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02124148
• Other study ID #: 15295
• Secondary ID: I4D-MC-JTJF
• Status: Completed
• Phase: Phase 1
• Start date: June 18, 2014
• Est. completion date: February 13, 2020

Study information

• Verified date: March 2020
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to investigate the safety of prexasertib in combination with other anti-cancer drugs (cisplatin, cetuximab, pemetrexed, fluorouracil or LY3023414) in participants with advanced cancer or cancer that has spread to another part of the body. The study has multiple parts (A, B, C, D and E). Participants will only enroll in one part.

Description:

The primary purpose of Parts A, B, C, D and E of this study is to determine a recommended dose level and schedule of prexasertib (an inhibitor of checkpoint kinase 1 and 2 [CHK1/CHK2] in combination with:

• cisplatin (Part A)

• cetuximab (Part B)

• pemetrexed (Part C)

• fluorouracil (Part D)

• LY3023414 (Part E) [An inhibitor of phosphoinositide 3-kinase alpha (PI3K alpha) and mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), and other class I phosphoinositide 3-kinase (PI3K) family members]

in participants with advanced or metastatic cancer.

Part A dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cisplatin in participants with advanced or metastatic cancer, Part B dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cetuximab in participants with advanced or metastatic colorectal cancer, Part C and D dose expansions have been removed and Part E dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with LY3023414 in participants with advanced or metastatic cancer, participants with PIK3CA mutations, or with advanced or metastatic breast cancer.

In Parts A and B the effect of adding granulocyte colony stimulating factor (G-CSF) to cisplatin in combination with prexasertib and cetuximab in combination with prexasertib will be explored. In Part A the effect of changing the schedule of prexasertib and cisplatin also will be explored. In Part B the effect of changing the schedule of prexasertib and cetuximab also will be explored.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: February 13, 2020
• Est. primary completion date: February 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed

• Have adequate organ function

• Prior Therapies: Systemic treatments: must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy at least 42 days and have discontinued any cytotoxic therapies at least 28 days prior to study enrollment. Radiation therapy and surgery: must be completed at least 4 weeks before study enrollment

• All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic

• Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin

• Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA

• Part E3 dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer

• Must be available during the duration of the study and willing to follow the study procedures

• Parts A and B: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for six months following the last dose of study drug

• Parts C, D and E: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug

• If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 14 days of the first dose of study drug and must not be breast feeding

• Part E: Are able to swallow capsules or tablets

Exclusion Criteria:

• Have received more than 2 previous lines of cytotoxic chemotherapy (if receiving cisplatin, 5-FU or pemetrexed)

• Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment

• Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C

• Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months

• Must not have a family history of long QTc syndrome

• Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome

• Must not have acute leukemia

• Part E: Have insulin-dependent (type I) diabetes or a history of gestational diabetes

• Part E: Prior treatment with a PI3K/mTOR inhibitor

Related Conditions & MeSH terms

• Breast Cancer
• Colorectal Neoplasms
• Neoplasm Metastasis
• Neoplasms

Intervention

Drug:
• Prexasertib
Administered IV
• Cisplatin
Administered IV
• Cetuximab
Administered IV
• G-CSF
Administered SC
• Pemetrexed
Administered IV
• Fluorouracil
Administered IV
• LY3023414
Administered PO
• Leucovorin
Administered IV

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin		Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Primary	Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab		Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Primary	Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed		Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Primary	Part D: Maximum Tolerated Dose of Prexasertib in Combination with Fluorouracil (5-FU)		Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Primary	Part E: Maximum Tolerated Dose of Prexasertib in Combination with LY3023414		Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)
Secondary	Pharmacokinetics: Maximum Plasma Concentration of Prexasertib		Cycle 1 Predose through Cycle 2, Day 15
Secondary	Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib		Cycle 1 Predose through Cycle 2, Day 15
Secondary	Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)		Cycle 1 Predose through Cycle 2, Day 1
Secondary	Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)		Cycle 1 Predose through Cycle 2, Day 1
Secondary	Pharmacokinetics: Maximum Plasma Concentration of Cetuximab		Cycle 1 Predose through Cycle 3, Day 1
Secondary	Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed		Cycle 1 Predose through Cycle 1, Day 2
Secondary	Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed		Cycle 1 Predose through Cycle 1, Day 2
Secondary	Pharmacokinetics: Maximum Plasma Concentration of 5-FU		Cycle 1 Predose through Cycle 1, Day 3
Secondary	Pharmacokinetics: Maximum Plasma Concentration of LY3023414		Cycle 1 Predose through Cycle 2, Day 2
Secondary	Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414		Time Frame: Cycle 1 Predose through Cycle 2, Day 2
Secondary	B2, E2, E3 Dose Expansion: Overall Response Rate		Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
Secondary	B2, E2, E3 Dose Expansion: Disease Control Rate		Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
Secondary	B2, E2, E3 Dose Expansion: Progression-Free Survival		Baseline through disease progression (estimated as up to 24 weeks) or death from any cause
Secondary	B2, E2, E3 Dose Expansion: Duration of Response		Baseline through disease progression (estimated as up to 24 weeks) or death from any cause

External Links

•   A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer