6G-15-2: An Open-Label, Phase 1/2a Dose Escalation Study of Safety and Efficacy of NEO100 in Recurrent Grade IV Glioma
Perillyl alcohol has previously been tested in 15 clinical studies in > 600 subjects This
includes 13 studies in 255 subjects using oral administration sponsored by the National
Cancer Institute and two studies in > 350 subjects using intranasal administration in
Brazil. NEO100 is a highly purified (>99%) form of perillyl alcohol. Studies in Brazil
suggest improved survival for patients with recurrent glioblastoma. Doses of 96 mg qid,
144mg qid, 192mg qid, and 288 mg qid administered intranasally to patients with recurrent
GBM for up to 6 months, disease progression or death. From 3 to 6 patients will be evaluated
after first cycle (28 days) until MTD is reached. MRI with gadolinium will be at base line,
and at the beginning of even cycles. A total of 25 patients will be treated at the MTD. PK
studies will be conducted during Phase 1 at first dosing, and after first dose of 3rd cycle.
2N-15-5: 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 will be
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
may be 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 is slow.
- Arm 1 will include 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 will include 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 will include 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 will include 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 will include any patients with leptomeningeal carcinomatosis with or without
evidence of active lesion at the baseline Gadoliniumenhanced brain MRI. Note: Previous
treatment with ALK inhibitors other than crizotinib is not allowed in Arms 1, 2, and 5.
Ceritinib will be administered orally once daily at a dose of 750 mg (five 150 mg capsules)
on a continuous dosing schedule. The treatment period will start on Cycle 1 Day 1.
Complete tumor assessments including gadolinium enhanced brain MRI will be 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 will include (S)AEs, physical examination, vital
signs, ECGs, laboratory parameters and WHO performance status. Blood and CSF samples for PK
will also be collected.
0C-14-2: An Open-Label, Phase 2 Study of Neratinib in Patients with Solid Tumors with Somatic Human Epidermal Growth Factor Receptor (Egfr, Her2, Her3) Mutations or EGFR Gene Amplification
This is an open-label, non-randomized, multicenter, multinational, Phase 2 study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in patients with ERBB mutation-positive or EGFR gene amplified solid tumors.
Neratinib (PB-272) is a small molecule that inhibits EGFR, HER2, and HER4. Aberrant expression of EGFR, HER2, and HER3 are linked to development of many epithelial cancers including colorectal, gastric, breast and head and neck cancers. Preclinical data suggest that neratinib will have antitumor activity in EGFR- and/or HER2-expressing carcinoma cell lines.
The study will include the following cohorts of patients with tumors harboring somatic ERBB (EGFR, ERBB2, ERBB3) mutations or EGFR gene amplification.
1. Bladder/Urinary Tract
ERBB2 Mutant - Neratinib 240mg daily + Paclitaxel 80mg/m^2 IV on Days 1, 8, and 15 of every 4 week cycle
2. Biliary Tract
ERBB2 mutant HR Negative- Neratinib 240mg daily
a. ERBB2 mutant HR Negative - Neratinib 240mg daily
b. ERBB2 mutant HR Positive - Neratinib 240mg daily + Fulvestrant 500mg on Days 1, 15 of the first month, then Day 1 of every 4 week cycle
ERBB2 mutant - Neratinib 240mg daily
ERBB2 mutant - Neratinib 240mg daily
ERBB2 mutant - Neratinib 240mg daily
7. Solid tumors (NOS)
ERBB2 Mutant - Neratinib 240 mg daily
*Cohorts given combination therapy are "Combination Therapy" and all cohorts given Neratinib alone are labeled "Monotherapy."
The following cohorts have closed to accrual:
1. EGFR mutation and/or EGFR amplification
Primary brain tumors
Cohort: Primary brain tumors (glioblastoma multiforme [GBM] Grade III, glioma, gliosarcoma)
Closed to Accrual
The trial will consist of a screening period, a treatment period, safety follow-up and end of treatment (EOT) assessments, follow-up for disease progression every 8 weeks, and a survival follow-up period.
Treatment will consist of neratinib by mouth with food once daily in the morning administered on a continuous basis or combination therapy as listed above.
The primary endpoint of this study for all cohorts is to determine the objective response rate at 8 weeks (ORR8) following treatment with neratinib.
The secondary objectives of this study are:
To determine the confirmed objective response rate (ORR) according to RECIST v1.1 or other defined response criteria with neratinib monotherapy and combination therapy.
To determine the clinical benefit rate (CBR) of neratinib monotherapy and combination therapy.
To determine PFS.
To determine change in tumor growth rate for patients with primary brain tumors.
To determine the duration of response (DOR) of neratinib monotherapy and combination therapy, defined as the time from which measurement criteria are met for overall response of CR and PR until the first date of documented disease progression.
To determine overall survival (OS).
To determine the role of dual modality PET/CT scans in measuring metabolic response to neratinib monotherapy and combination therapy.
To assess the safety profile and tolerability of neratinib monotherapy and combination therapy.
To assess Patient Reported Outcomes using the EuroQol EQ-5D-5L instrument.
A Simon 2-stage optimal design will be used to determine whether neratinib has sufficient activity to warrant further development in the following cohorts: colorectal, endometrial, gastroesophageal, ovarian, and listed breast cancers. At the end of the trial, a 2-sided 80% confidence interval for Objective Response Rate will be determined for each cohort separately using the method of Koyama and Chen (2008).
Patient-related outcomes (EQ-5D-5L instrument) will be summarized and plotted over time. Changes from baseline will be provided with both point estimates and confidence intervals.
All analyses are descriptive and no formal testing is planned.
Recruiting | Any Cancer Condition or Solid Tumor | Multisite