PALBOCICLIB + PD-0325901 for NSCLC and Solid Tumors
Phase: Phase 1/Phase 2
Diagnosis: Solid Tumor/Phase I
NCT ID: NCT02022982
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-506
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.
Dana-Farber Cancer Institute, Brigham and Women's Hospital
Geoffrey Shapiro, MD, PhD,
Dana-Farber Cancer Institute
Dana-Farber Cancer Institute:
Andrew Wolanski, 617-632-6623,
- 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
- Patients must have recovered to ≤ Grade 1 in terms of toxicity from prior treatments
(excluding neuropathy which can be ≤ Grade 2).
- 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
- 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
- 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
- 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.