Solid Tumors Clinical Trial
Official title:
Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor PD-0325901 for Patients With KRAS Mutant Non-Small Cell Lung Cancer and Other Solid Tumors
NCT number | NCT02022982 |
Other study ID # | 13-506 |
Secondary ID | |
Status | Completed |
Phase | Phase 1 |
First received | |
Last updated | |
Start date | January 2014 |
Est. completion date | June 30, 2021 |
Verified date | March 2024 |
Source | Dana-Farber Cancer Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This research study is evaluating the experimental drug palbociclib in combination with another experimental drug PD-0325901 as a possible treatment for cancers with KRAS mutations, particularly for those which started in the lung.
Status | Completed |
Enrollment | 60 |
Est. completion date | June 30, 2021 |
Est. primary completion date | November 1, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Dose-escalation/MTD cohorts, participants must have histologically confirmed malignancy with a RAS mutation that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. For the randomized phase 2 component of the study, participants must have histologically confirmed NSCLC with a confirmed KRAS mutation (via any CLIA-certified method) - For the dose-escalation component, participants are required to have only evaluable disease. For the MTD cohort and phase 2 component of the study, participants must have measurable disease. - Participants enrolled to the MTD cohort must agree to pre and on-treatment tumor biopsies if assessable disease is identified. - Age =18 years. - ECOG performance status = 2 (see Appendix A). Participants must have normal organ and marrow function as defined below: - Absolute neutrophils count = 1,500/mcL - Platelets =100,000/mcL - total bilirubin within normal institutional limits - AST (SGOT)/ALT (SGPT) = 2.5 X institutional upper limit of normal (= 5.0 X institutional upper limit of normal permitted if hepatic metastases present) - Creatinine within 1.5x the ULN institutional limits. - Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Ability to understand and the willingness to sign a written informed consent document. - QTc =480 msec. - The availability of archival tissue to evaluate retrospectively the participant's Rb status - Patients must have recovered to = Grade 1 in terms of toxicity from prior treatments (excluding neuropathy which can be = Grade 2). Exclusion Criteria: - Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. - Participants may not be receiving any other study agents concurrently with the study drugs. - Participants with symptomatic brain metastases that require chronic steroids are excluded. Patients with a history of brain metastases are permitted to enroll as long as they have been treated, off of steroids and have been stable for one month on imaging. - Concurrent use with strong CYP3A4 inhibitors/inducers is prohibited due to drug-drug interactions with palbociclib. - Due to potential drug interactions between warfarin and PD-0325901, warfarin use is excluded. Other anticoagulants are permitted. - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant women are excluded from this study because the study agents have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued. - For Part II only: Individuals with a history of a different malignancy are ineligible except if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. - HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. - Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for ocular toxicity, such as risk factors for retinal vein occlusion, related to PF-0325901. |
Country | Name | City | State |
---|---|---|---|
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Dana-Farber Cancer Institute |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety and tolerability | Toxicities will be graded using version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE). | 2 Years | |
Primary | Maximum Tolerated Dose and Recommended Phase 2 Dose | A standard 3+3 design will be implemented to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of study drugs. A dose will be declared the MTD if zero or 1 patient out of 6 experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. This is generally the RP2D. | 2 years | |
Secondary | Maximum plasma concentration (Cmax) of palbociclib | Cmax (ng/ml) of palbociclib will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Time to maximum concentration (tmax) of palbociclib | tmax (h) of palbociclib will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | AUC-12 of palbociclib | The AUC-12 (ng.h/ml) of palbociclib will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Clearance (CL/F) of palbociclib | Clearance (L/h) of palbociclib will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Maximum plasma concentration (Cmax) of PD-0325901 | Cmax (ng/ml) of PD-0325901 will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Time to maximum concentration (tmax) of PD-0325901 | tmax of PD-0325901 will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | AUC-12 of PD-0325901 | AUC-12 (ng.h/ml) of PD-0325901 will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Clearance (CL/F ) of PD-0325901 | Clearance (L/h) of PD-0325901 will be assessed utilizing serial blood draws on cycle 1 day 1 and on cycle 1 day 15 (steady state). | 1 month | |
Secondary | Target engagement of palbociclib by immunohistochemistry (IHC) of phospho-Rb in tumor | IHC for phospho-Rb will be performed in pre- and on-treatment tumor biopsies to assess palbociclib target engagement. | 2 Years | |
Secondary | Target engagement of palbociclib by immunohistochemistry (IHC) of phospho-Rb in skin | IHC for phospho-Rb will be performed in pre- and on-treatment skin biopsies to assess palbociclib target engagement. | 2 Years | |
Secondary | Target engagement of PD-0325901 by immunohistochemistry (IHC) of phospho-ERK in tumor | IHC for phospho-ERK will be performed in pre- and on-treatment tumor biopsies to assess PD-0325901 target engagement. | 2 Years | |
Secondary | Cell cycle arrest by palbociclib using serum thymidine kinase 1 (TK1) assays | Serial serum collections (pre- and on-treatment) will be assayed for TK1 activity to assess cell cycle arrest mediated by palbociclib. | 2 Years | |
Secondary | Quantitative non-invasive genotyping for KRAS in cfDNA | Serial cfDNA samples will be collected and assessed for KRAS plasma allellic burden as a measure of anti-tumor activity of the combination of palbociclib and PD-0325901. | 2 Years | |
Secondary | Overall Response Rate | The preliminary clinical efficacy of palbociclib and PD-0325901 in advanced KRAS-mutant solid tumors will be assessed using CT and MRI scans per RECIST version 1.1. | 2 Years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT00750841 -
Study of the Effect of Rifampicin on the Pharmacokinetics (PK) of Multiple Doses of Cediranib in Patients With Solid Tumours
|
Phase 1 | |
Withdrawn |
NCT05419817 -
Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System
|
Phase 2 | |
Completed |
NCT02828930 -
A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)
|
Phase 1 | |
Completed |
NCT01197170 -
Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
|
Phase 1 | |
Completed |
NCT03258515 -
A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
|
Phase 1 | |
Terminated |
NCT03225105 -
M3541 in Combination With Radiotherapy in Solid Tumors
|
Phase 1 | |
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Completed |
NCT01878890 -
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
|
Phase 1 | |
Active, not recruiting |
NCT05059522 -
Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing
|
Phase 3 | |
Active, not recruiting |
NCT03634982 -
Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04685226 -
A Phase I/II Clinical Trial of ICP-723 in the Treatment of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT06036121 -
A Study of ADRX-0706 in Select Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
Completed |
NCT01528046 -
Metformin in Children With Relapsed or Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05325866 -
A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
|
Phase 1/Phase 2 | |
Recruiting |
NCT04557449 -
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
|
Phase 1/Phase 2 | |
Terminated |
NCT02890368 -
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
|
Phase 1 | |
Completed |
NCT02759640 -
A Phase I Trial of HS-10241 in Solid Tumors
|
Phase 1 | |
Withdrawn |
NCT01940601 -
Pharmacodynamics, Pharmacokinetics, Efficacy and Safety of Balugrastim in Pediatric Patients With Solid Tumors
|
Phase 2 |