Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
A Phase 1 Study of Crizotinib in Combination With Conventional Chemotherapy for Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
4 other identifiers
interventional
46
2 countries
23
Brief Summary
This phase I trial studies the side effects and the best dose of crizotinib when given together with combination chemotherapy in treating younger patients with solid tumors or anaplastic large cell lymphoma that has returned or does not respond to treatment. Crizotinib may stop the growth of tumor or cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, topotecan hydrochloride, dexrazoxane hydrochloride, doxorubicin hydrochloride, and vincristine sulfate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving crizotinib together with combination chemotherapy may be a better treatment for patients with solid tumors or anaplastic large cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2013
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2012
CompletedFirst Posted
Study publicly available on registry
May 28, 2012
CompletedStudy Start
First participant enrolled
April 29, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2018
CompletedResults Posted
Study results publicly available
January 5, 2024
CompletedJanuary 5, 2024
December 1, 2023
5.7 years
May 24, 2012
October 6, 2023
December 13, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose (MTD) of Crizotinib
The MTD of crizotinib administered with combination chemotherapy based on the incidence of dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by NCI CTCAE version 4.0.
Up to 21 days
Number of Patients With Dose Limiting Toxicity (DLT)
Number of patients of all DLT reported as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. stratified by dose level and study part.
Up to 21 days
Area Under the Concentration
Median (min, max) of the area under the concentration time curve for crizotinib assessed in course 1 at 1, 2, 4, 6-8 hours, and 15-21 days post-administration stratified by dose level and study part.
Up to 21 days
Secondary Outcomes (6)
Response Rate
Up to 2 years
ALK Status and Response to Crizotinib
up to 2 years
MRD Status and Response to Crizotinib
Up to 2 years
ALK Expression for Crizotinib
Up to 7 days
Acceptability of Crizotinib Capsule Formulation Palatability
Up to 1 week
- +1 more secondary outcomes
Study Arms (4)
Part A (crizotinib, cyclophosphamide, topotecan hydrochloride)
EXPERIMENTALPatients receive crizotinib (oral solution) PO BID on days 1-21, cyclophosphamide IV QD on days 1-5, and topotecan hydrochloride IV QD on days 1-5. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/3/14)
Part B (crizotinib, vincristine, dexrazoxane, doxorubicin)
EXPERIMENTALPatients receive crizotinib (oral solution) PO BID as in Part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/3/14)
Part C (crizotinib, cyclophosphamide, topotecan hydrochloride)
EXPERIMENTALPatients receive crizotinib (capsule formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Part D (crizotinib, cyclophosphamide, topotecan hydrochloride)
EXPERIMENTALPatients receive crizotinib (microsphere formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Given IV
Given IV
Given IV
Correlative studies
Correlative studies
Ancillary studies
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have had histologic verification of malignancy at original diagnosis or relapse; all patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL) are eligible except for patients with primary or metastatic central nervous system (CNS) tumors or patients with primary cutaneous ALCL
- Patients must have either measurable or evaluable disease
- Patients current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
- Karnofsky \>= 60% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; Note: patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
- Myelosuppressive chemotherapy:
- Solid tumors: at least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
- ALCL:
- Patients with ALCL who relapse while receiving standard maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study
- Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy; at least 14 days must have elapsed after the completion of cytotoxic therapy
- Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
- Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
- Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
- Radiation therapy (XRT):
- +25 more criteria
You may not qualify if:
- Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible
- Patients who are currently receiving another investigational drug are not eligible
- Patients who are currently receiving other anti-cancer agents are not eligible
- Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
- Patients chronically receiving medications known to be metabolized by cytochrome P 450, family 3, subfamily A, polypeptide 4 (CYP3A4) and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
- Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
- Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John?s wort are not eligible; the topical use of these medications (if applicable) is allowed
- Patients receiving PPIs and H2 blockers are not eligible for Part D
- Patients who have an uncontrolled infection are not eligible
- Patients who have received a prior solid organ transplantation are not eligible
- Patients who have a primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Parts A and B: Patients who are able to swallow liquid or use a nasogastric or gastrostomy (G) tube are eligible
- Part C: Patients must be able to swallow intact capsules
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (23)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, 30322, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University/Herbert Irving Cancer Center
New York, New York, 10032, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (1)
Greengard E, Mosse YP, Liu X, Minard CG, Reid JM, Voss S, Wilner K, Fox E, Balis F, Blaney SM, Adamson PC, Weigel BJ. Safety, tolerability and pharmacokinetics of crizotinib in combination with cytotoxic chemotherapy for pediatric patients with refractory solid tumors or anaplastic large cell lymphoma (ALCL): a Children's Oncology Group phase 1 consortium study (ADVL1212). Cancer Chemother Pharmacol. 2020 Dec;86(6):829-840. doi: 10.1007/s00280-020-04171-4. Epub 2020 Oct 23.
PMID: 33095287DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Emily Greengard
COG Phase I Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 24, 2012
First Posted
May 28, 2012
Study Start
April 29, 2013
Primary Completion
December 31, 2018
Study Completion
December 31, 2018
Last Updated
January 5, 2024
Results First Posted
January 5, 2024
Record last verified: 2023-12