A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02124148 |
|
Recruitment Status :
Completed
First Posted : April 28, 2014
Last Update Posted : April 1, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neoplasm Metastasis Colorectal Neoplasms Breast Cancer | Drug: Prexasertib Drug: Cisplatin Drug: Cetuximab Drug: G-CSF Drug: Pemetrexed Drug: Fluorouracil Drug: LY3023414 Drug: Leucovorin | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 167 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1b Trial of LY2606368 in Combination With Chemotherapy or Targeted Agents in Advanced and/or Metastatic Tumors |
| Actual Study Start Date : | June 18, 2014 |
| Actual Primary Completion Date : | February 13, 2020 |
| Actual Study Completion Date : | February 13, 2020 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Prexasertib + Cisplatin (Part A)
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
Administered IV
Other Name: LY2606368 Drug: Cisplatin Administered IV Drug: G-CSF Administered SC |
|
Experimental: Prexasertib + Cetuximab (Part B)
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
Administered IV
Other Name: LY2606368 Drug: Cetuximab Administered IV
Other Name: Erbitux Drug: G-CSF Administered SC |
|
Experimental: Prexasertib + Pemetrexed (Part C)
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
Administered IV
Other Name: LY2606368 Drug: Pemetrexed Administered IV
Other Name: Alimta |
|
Experimental: Prexasertib + 5-FU (Part D)
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
Administered IV
Other Name: LY2606368 Drug: Fluorouracil Administered IV Drug: Leucovorin Administered IV |
|
Experimental: Prexasertib + LY3023414 (Part E)
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
Administered IV
Other Name: LY2606368 Drug: LY3023414 Administered PO |
- Part A: Maximum Tolerated Dose and Schedule of Prexasertib in Combination with Cisplatin [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
- Part B: Maximum Tolerated Dose of Prexasertib in Combination with Cetuximab [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
- Part C: Maximum Tolerated Dose of Prexasertib in Combination with Pemetrexed [ Time Frame: 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) [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
- Part E: Maximum Tolerated Dose of Prexasertib in Combination with LY3023414 [ Time Frame: Cycle 1 predose through last dose last cycle (estimated up to 24 weeks) ]
- Pharmacokinetics: Maximum Plasma Concentration of Prexasertib [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
- Pharmacokinetics: Area Under the Plasma Concentration Curve of Prexasertib [ Time Frame: Cycle 1 Predose through Cycle 2, Day 15 ]
- Pharmacokinetics: Maximum Plasma Concentration of Cisplatin (Total Platinum) [ Time Frame: Cycle 1 Predose through Cycle 2, Day 1 ]
- Pharmacokinetics: Area Under the Plasma Concentration Curve of Cisplatin (Total Platinum) [ Time Frame: Cycle 1 Predose through Cycle 2, Day 1 ]
- Pharmacokinetics: Maximum Plasma Concentration of Cetuximab [ Time Frame: Cycle 1 Predose through Cycle 3, Day 1 ]
- Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed [ Time Frame: Cycle 1 Predose through Cycle 1, Day 2 ]
- Pharmacokinetics: Area Under the Plasma Concentration Curve of Pemetrexed [ Time Frame: Cycle 1 Predose through Cycle 1, Day 2 ]
- Pharmacokinetics: Maximum Plasma Concentration of 5-FU [ Time Frame: Cycle 1 Predose through Cycle 1, Day 3 ]
- Pharmacokinetics: Maximum Plasma Concentration of LY3023414 [ Time Frame: Cycle 1 Predose through Cycle 2, Day 2 ]
- Pharmacokinetics: Area Under the Plasma Concentration Curve of LY3023414 [ Time Frame: Time Frame: Cycle 1 Predose through Cycle 2, Day 2 ]
- B2, E2, E3 Dose Expansion: Overall Response Rate [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
- B2, E2, E3 Dose Expansion: Disease Control Rate [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
- B2, E2, E3 Dose Expansion: Progression-Free Survival [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
- B2, E2, E3 Dose Expansion: Duration of Response [ Time Frame: Baseline through disease progression (estimated as up to 24 weeks) or death from any cause ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02124148
| United States, Florida | |
| Florida Cancer Specialists | |
| Sarasota, Florida, United States, 34232 | |
| United States, Oklahoma | |
| University of Oklahoma Health Sciences Center | |
| Oklahoma City, Oklahoma, United States, 73104 | |
| United States, Tennessee | |
| Sarah Cannon Research Institute SCRI | |
| Nashville, Tennessee, United States, 37203 | |
| Tennessee Oncology PLLC | |
| Nashville, Tennessee, United States, 37203 | |
| United States, Texas | |
| University of Texas MD Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Study Director: | 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT02124148 |
| Other Study ID Numbers: |
15295 I4D-MC-JTJF ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | April 28, 2014 Key Record Dates |
| Last Update Posted: | April 1, 2020 |
| Last Verified: | March 2020 |
|
cancer |
|
Neoplasms Neoplasm Metastasis Colorectal Neoplasms Neoplastic Processes Pathologic Processes Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Leucovorin |
Fluorouracil Pemetrexed Cetuximab Prexasertib Antineoplastic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antidotes Protective Agents Vitamin B Complex Vitamins |