A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression
Safety follow-up: After discontinuation of study treatment, all subjects were followed for
safety for 30 days except in the case of death, loss to follow up, withdrawal of consent, or
discontinuation of study treatment to enroll in the ribociclib rollover clinical trial
(CLEE011X2X01B).
Disease progression follow-up: Subjects who discontinued study drug for any reasons other
than disease progression were followed for efficacy every 8 weeks during the first 12 months.
After 12 months, they were followed for every 12 weeks until disease progression, death,
discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of
consent), the initiation of a new antineoplastic treatment, or until all subjects had been
followed for at least 18 months after their first dose of study drug, or early study
termination, whichever occurred first.
Survival follow-up: All subjects were followed for survival via a phone call (or during a
clinic visit) every 12 weeks and up to one additional time per quarter if a survival update
was required to meet safety or regulatory needs. The safety follow-up was carried out until
any of the following occurred (whichever occurred first): death, withdrawal of consent, loss
to follow-up, at least 18 months had elapsed from when the last subject had started
treatment, or when 80% of subjects had died or were lost to follow-up, or early study
termination.
BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments
This is a phase II, multicenter, open-label, three-cohort, non-comparative study of alpelisib
plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2- aBC
harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after prior
treatments.
The study includes two phases:
- Core Phase: includes treatment phase for all patients from First Patient First Treatment
(FPFT) until 18 months post Last Patient First Treatment (LPFT) + 1 month Safety
follow-up (total 19 months post LPFT)
- Extension Phase: includes treatment phase starting at the end of the treatment Core
Phase up to 36 months. The extension treatment phase is only for patients who are
continuing to benefit from treatment at the end of the Core Phase and are not eligible
for PSDS (Post-Study Drug Supply) in their country based on local regulations. Patients
will continue on their existing treatment assigned in the Core Phase. If PSDS becomes
available for a patient, the patient should be discontinued from the study and access
treatment via PSDS. During the Extension Phase there will be no per protocol efficacy
assessments other than physician's determination as per standard of care of whether or
not the patient is continuing to derive clinical benefit from the study treatment.
Patients who are benefiting from treatment and are eligible for PSDS will exit the trial at
the end of the Core Phase.
After discontinuation of study treatment, all patients will be followed for safety for at
least 30 days except in case of death, loss to follow-up or withdrawal of consent.
During the Core Phase only: If a patient discontinues study treatment for reasons other than
documented disease progression, death, lost to follow-up, or withdrawal of consent for
efficacy follow-up, tumor assessments should continue to be performed until documented
disease progression, death, lost to follow-up, or withdrawn consent to efficacy follow-up or
end of study (Post-treatment efficacy follow-up). Moreover, all participants will be followed
for survival status (after progression) regardless of treatment discontinuation reason
(except if consent is withdrawn, death or patient is lost to follow-up) until death, lost to
follow-up, or withdrawal of consent for survival follow-up or end of the Core Phase
A Phase II, Multi-center, Open-label, Five-arm Study to Evaluate the Efficacy and Safety of Oral Ceritinib Treatment for Patients With ALK-positive Non-small Cell Lung Cancer (NSCLC) Metastatic to the Brain and/or to Leptomeninges
Approximately 160 patients diagnosed with ALK-positive metastatic NSCLC (according to the 7th
edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual) and active
lesions in the brain and/or diagnosed with leptomeningeal carcinomatosis were included in the
study, approximately 40 patients in Arm 1 and Arm 2, approximately 30 patients in Arms 3 and
Arm 4, and approximately 20 patients in Arm 5. Additional patients were enrolled in Arm 4 to
achieve approximately 60 patients in Arms 3 and 4 together (i.e. ALKi naïve patients), if
enrollment rate in Arm 3 was slow.
- Arm 1 included patients with metastases in the brain without evidence of leptomeningeal
carcinomatosis, previously treated with radiation to the brain and with prior exposure
to an ALKi.
- Arm 2 included patients with metastases in the brain without evidence of leptomeningeal
carcinomatosis, previously untreated with radiation to the brain but with prior exposure
to an ALKi.
- Arm 3 included patients with metastases in the brain without evidence of leptomeningeal
carcinomatosis, previously treated with radiation to the brain but with no prior
exposure to an ALKi.
- Arm 4 included patients with metastases in the brain without evidence of leptomeningeal
carcinomatosis, previously untreated with radiation to the brain and with no prior
exposure to an ALKi
- Arm 5 included any patients with leptomeningeal carcinomatosis with or without evidence
of active lesion at the baseline Gadolinium-enhanced brain MRI.
Note: Previous treatment with ALK inhibitors other than crizotinib was not allowed in Arms 1,
2, and 5.
Ceritinib was administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a
continuous dosing schedule. The treatment period started on Cycle 1 Day 1.
Complete tumor assessments including gadolinium enhanced brain MRI was repeated at Week 8 (on
Cycle 3 Day 1) and every 8 weeks (i.e. every 2 cycles) thereafter or earlier if clinically
indicated. Safety evaluations included (S)AEs, physical examination, vital signs, ECGs,
laboratory parameters and WHO performance status. Blood and CSF samples for PK were also
collected.
A Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Myeloid Malignancies
The anti-leukemia therapies are defined as follows:
- Venetoclax (Ven)
- Azacitidine (Aza)
- Mitoxantrone, etoposide, and cytarabine (MEC)
This study consists of 3 safety run-in cohorts;
- Safety Run-in Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Safety Run-in Cohort 2 (R/R AML Mag + MEC)
- Safety Run-in Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Participants will receive treatment at the assigned dose level for at least 4 cycles in the
Safety Run-in cohorts, after which they may continue at the assigned dose level or switch to
the RP2D upon agreement between the investigator and the sponsor. After completion of each
safety run-in cohort and identification of the RP2D for that cohort, participants may be
enrolled into the corresponding Phase 2 cohorts;
- Phase 2 Cohort 1 (1L Unfit AML Mag + Ven + Aza)
- Phase 2 Cohort 2 (R/R AML Mag + MEC)
- Phase 2 Cohort 3 (Post-chemo Maintenance Mag + CC-486)
Cycle length is 28 days for both the Safety Run-in and Phase 2 cohorts.
Note: All cohorts are closed to screening and enrollment.
A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer
Subjects enrolled in Cohort A (Monotherapy Population) were required to have relapsed or
progressed on at least one platinum based chemotherapy regimen prior to enrollment (i.e.
dabrafenib was no less than second line treatment for metastatic disease). Additional lines
of prior anti-cancer therapy were allowed. Subjects received dabrafenib as a single agent at
the recommended dose of 150 mg twice daily. A 2 stage design with a planned sample size of 40
subjects was initially used for Cohort A.
Subjects enrolled in Cohort B (Combination Second-Line Population) were required to have
relapsed or progressed on at least one platinum based chemotherapy prior to enrollment but
did not receive more than 3 prior systemic anti-cancer therapies (i.e. dabrafenib/trametinib
were second, third, or fourth line treatment for metastatic disease). Subjects received the
recommended dose of both drugs (dabrafenib 150 mg twice daily and trametinib 2 mg once
daily).
Subjects enrolled in Cohort C (Combination First-Line Population) did not receive prior
systemic anti-cancer therapies for metastatic disease (i.e. dabrafenib/trametinib was first
line treatment for metastatic disease). Subjects received the recommended dose of both drugs
(dabrafenib 150 mg twice daily and trametinib 2 mg once daily).
Crossover: Subjects receiving and adequately tolerating dabrafenib as a single agent and who
continued to meet the inclusion and exclusion criteria (including the additional criteria for
combination therapy) had the option to crossover to dabrafenib (150 mg BID) and trametinib (2
mg once daily) combination treatment at the time of radiologic disease progression with prior
approval from a Medical Lead. If a subject was receiving less than 150 mg BID of dabrafenib
at the time of the crossover, the subject was to continue at the lower dose of dabrafenib
when initiating combination therapy.
Pilot Study of Resection and GammaTile Followed by Concomitant External Beam Radiation Therapy (EBRT) and Temozolomide (TMZ) and Adjuvant in Newly Diagnosed Glioblastoma (GBM)
This study seeks to explore if GT, given its unique radiobiological and physical
characteristics, may permit safe dose escalation and intensification and thereby provide a
benefit to newly diagnosed GBM patients in terms of OS and LC when incorporated into the
framework of the Stupp protocol. In this study, GT is utilized as an upfront boost at the
time of maximum safe resection and dosimetrically integrated into what is otherwise standard
of care therapy.
Patients in this study will receive doses from two different forms of radiation treatment,
initially from Cs-131 BT with GT and subsequently from fractionated EBRT. In order to ensure
both patient safety and adequacy of treatment, we have chosen to stipulate and evaluate the
coverage of the tumor volumes and OARs using the doses combined from both these treatments.
The intention is that with this methodology the doses received by the target volumes and
relevant OARs from the implanted Cs-131 will be accounted for during EBRT treatment planning.
This dose combination, accomplished using radiobiological modeling, is frequently undertaken
in breast, prostate, and gynecological malignancies. To provide oversight and planning
feedback, the first three patients enrolled at each site will undergo review by the Clinical
Oversight Committee (COC) at two points for each patient, once after the GT implant, and
before starting EBRT treatment.
A Phase 1 Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of CLN-418 in Subjects With Advanced Solid Tumors
This is a study to evaluate the safety and tolerability of the study drug CLN-418, and to
determine the maximum tolerated dose and/or recommended Phase 2 study dose of CLN-418.
The study will also look at the anti-tumor activity, pharmacokinetics and immunogenicity of
CLN-418.The study consists of 2 parts. In Part 1, patients are enrolled into different cohort
doses in order to identify the appropriate recommended phase 2 dose (RP2D) or maximum
tolerated dose (MTD). In Part 2, participants with metastatic / unresectable Non small cell
lung cancer (NSCLC), Triple Negative Breast Cancer (TNBC) will receive the maximum tolerated
dose (MTD) and/or recommended phase 2 dose (RP2D) established in Part 1 of the study. In Part
1 and Part 2, participants will be administered treatment every 3 weeks.
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