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

NCT02124148 | Completed Phase 1

• 2 other identifiers: 15295I4D-MC-JTJF
• Study Type: interventional
• Target: 167
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Neoplasm Metastasis; Colorectal Neoplasms; Breast Cancer

Keywords

cancer

Outcome Measures

Primary Outcomes (5)

• 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)

• Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab

  Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)

• Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed

  Cycle 1 predose through last dose last cycle (estimated up to 24 weeks)

• 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)

• 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 Outcomes (14)

• Pharmacokinetics: Maximum Plasma Concentration of Prexasertib

  Cycle 1 Predose through Cycle 2, Day 15

• Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib

  Cycle 1 Predose through Cycle 2, Day 15

• Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum)

  Cycle 1 Predose through Cycle 2, Day 1

• Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum)

  Cycle 1 Predose through Cycle 2, Day 1

• Pharmacokinetics: Maximum Plasma Concentration of Cetuximab

  Cycle 1 Predose through Cycle 3, Day 1

Study Arms (5)

Prexasertib + Cisplatin (Part A)

EXPERIMENTAL

Part A: Prexasertib and cisplatin administered intravenously (IV) once every 21 days. Part A2: Prexasertib and cisplatin administered IV every 21 days; G-CSF administered subcutaneously (SC) starting approximately 24 hours after each prexasertib dose every 21 days. Part A3: Cisplatin administered IV on day one and prexasertib administered IV on day two once every 21 days. Part A Expansion: Part A, A2, and/or A3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met.

Drug: Prexasertib; Drug: Cisplatin; Drug: G-CSF

Prexasertib + Cetuximab (Part B)

EXPERIMENTAL

Part B: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days. Part B2: Cetuximab administered IV weekly and prexasertib administered IV once every 14 days; G-CSF administered SC starting approximately 24 hours after each prexasertib dose every 14 days. Part B3: Cetuximab administered IV with prexasertib administered IV once every 14 days. Part B Expansion: Part B, B2 and/or B3 may be expanded at the recommended dose. Participants may remain on treatment until discontinuation criteria are met.

Drug: Prexasertib; Drug: Cetuximab; Drug: G-CSF

Prexasertib + Pemetrexed (Part C)

EXPERIMENTAL

Part C: Pemetrexed administered IV on day one and prexasertib administered IV on day one and two every 21 days. Participants may remain on treatment until discontinuation criteria are met.

Drug: Prexasertib; Drug: Pemetrexed

Prexasertib + 5-FU (Part D)

EXPERIMENTAL

Part D: Leucovorin administered IV on day one, 5-FU administered IV bolus on day one and by continuous IV on days one to three (46 hours), and prexasertib administered IV on day three every 14 days. Participants may remain on treatment until discontinuation criteria are met.

Drug: Prexasertib; Drug: Fluorouracil; Drug: Leucovorin

Prexasertib + LY3023414 (Part E)

EXPERIMENTAL

Part E: Prexasertib administered IV on day one and LY3023414 administered orally twice daily every 14 days. Part E will be expanded at the recommended dose in participants with advanced or metastatic cancer, participants with PIK3CA mutations (E2 expansion), or with advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer (E3 expansion). Participants may remain on treatment until discontinuation criteria are met.

Drug: Prexasertib; Drug: LY3023414

Interventions

Prexasertib DRUG

Administered IV

Also known as: LY2606368

Prexasertib + 5-FU (Part D); Prexasertib + Cetuximab (Part B); Prexasertib + Cisplatin (Part A); Prexasertib + LY3023414 (Part E); Prexasertib + Pemetrexed (Part C)

Cisplatin DRUG

Administered IV

Prexasertib + Cisplatin (Part A)

Cetuximab DRUG

Administered IV

Also known as: Erbitux

Prexasertib + Cetuximab (Part B)

G-CSF DRUG

Administered SC

Prexasertib + Cetuximab (Part B); Prexasertib + Cisplatin (Part A)

Pemetrexed DRUG

Administered IV

Also known as: Alimta

Prexasertib + Pemetrexed (Part C)

Fluorouracil DRUG

Administered IV

Prexasertib + 5-FU (Part D)

LY3023414 DRUG

Administered PO

Prexasertib + LY3023414 (Part E)

Leucovorin DRUG

Administered IV

Prexasertib + 5-FU (Part D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Moore KN, Hong DS, Patel MR, Pant S, Ulahannan SV, Jones S, Meric-Bernstam F, Wang JS, Aljumaily R, Hamilton EP, Wittchen ES, Wang X, Lin AB, Bendell JC. A Phase 1b Trial of Prexasertib in Combination with Standard-of-Care Agents in Advanced or Metastatic Cancer. Target Oncol. 2021 Sep;16(5):569-589. doi: 10.1007/s11523-021-00835-0. Epub 2021 Sep 24.

  PMID: 34559360 DERIVED

• Hong DS, Moore KN, Bendell JC, Karp DD, Wang JS, Ulahannan SV, Jones S, Wu W, Donoho GP, Ding Y, Capen A, Wang X, Bence Lin A, Patel MR. Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor. Clin Cancer Res. 2021 Apr 1;27(7):1864-1874. doi: 10.1158/1078-0432.CCR-20-3242. Epub 2021 Jan 25.

  PMID: 33495309 DERIVED

Related Links

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

MeSH Terms

Conditions

Neoplasm Metastasis; Colorectal Neoplasms; Breast Neoplasms; Neoplasms

Interventions

prexasertib; Cisplatin; Cetuximab; Granulocyte Colony-Stimulating Factor; Pemetrexed; Fluorouracil; LY3023414; Leucovorin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2014
• First Posted: April 28, 2014
• Study Start: June 18, 2014
• Primary Completion: February 13, 2020
• Study Completion: February 13, 2020
• Last Updated: April 1, 2020

Record last verified: 2020-03

Locations

US (5)