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An Open Label, Multicenter Phase I/II Study Of Selective Cyclin Dependent Kinase Inhibitor P276-00 In Combination With Radiation In Subjects With Recurrent And/Or Locally Advanced Squamous Cell Carcinoma Of Head And Neck


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Squamous Cell Carcinoma of Head and Neck

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Trial Information

An Open Label, Multicenter Phase I/II Study Of Selective Cyclin Dependent Kinase Inhibitor P276-00 In Combination With Radiation In Subjects With Recurrent And/Or Locally Advanced Squamous Cell Carcinoma Of Head And Neck


This is an open label single arm multicenter trial to evaluate safety and efficacy of
P276-00 in combination with radiation in patients with recurrent and/or locally advanced
squamous cell carcinoma of head and neck. The Primary objective of this study is to
determine maximum tolerated dose (MTD) and dose limiting toxicity (ies) (DLT/s) of P276-00
in combination with radiation in subjects with recurrent and/or locally advanced squamous
cell carcinoma of head and neck (SCCHN). The Secondary objectives are 1. To evaluate safety
and tolerability of the combination regimen of P276-00 and radiation in the study population
2. To analyze pharmacokinetics (PK) of P276-00 in the study population 3. To evaluate
efficacy of the combination regimen of P276-00 and radiation in the study population 4. To
perform exploratory analysis of biomarkers associated with use of P276-00 and radiation in
the study population. In phase 1 component,a cohort of 3 subjects will be enrolled at
starting dose level of P276-00 which is 100 mg/m2/day to be given intravenously from day 1
to day 5 in 21 day cycle for 2 cycles in combination with radiation. If this dose is well
tolerated then next cohort will be enrolled at higher dose level of P276-00. P276-00 dose
escalation will continue until MTD of P276-00 in combination with Radiation is determined.
The subsequent dose levels of P276-00 will be 140 mg/m2/day and 185 mg/m2/day.

In phase 2 component 10 subjects will be enrolled at this MTD of P276-00 in combination with
radiation to evaluate efficacy. Dose of radiation for both phases is 60 Gy over 6 weeks.
Safety evaluations will be conducted at regular intervals during the study. Tumor
measurements will be undertaken at baseline, at the end of cycle 2 and 5 to 6 weeks after
end of cycle 2. Response evaluation will be performed by Response Evaluation Criteria in
Solid Tumors (RECIST). Subjects showing stable disease or better response at the last
assessment will be followed up for tumor measurements until progression or recurrence of
disease.


Inclusion Criteria:



1. Disease specifications:

- Phase I component: Radiation naïve subjects with histologically and/ or
cytologically confirmed squamous cell carcinoma of head and neck that is
non-metastatic, unresectable and recurrent. Radiation naïve subjects with
non-recurrent, non-metastatic, unresectable, disease can also be enrolled if
he/she is intolerant to and/or unwilling for chemoradiotherapy involving
standard cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU,
taxanes, methotrexate, etc)

- Phase II component: Radiation naïve subjects with non-recurrent, non-metastatic,
unresectable, locally advanced squamous cell carcinoma of head and neck who are
intolerant to and/or unwilling for chemoradiotherapy involving standard
cytotoxic agents (e.g. cisplatin, carboplatin, oxaliplatin, 5-FU, taxanes,
methotrexate, etc).

2. Treatment specifications:

- Phase I Component: subjects must not have received any treatment (chemotherapy,
targeted or biologic agents, radiotherapy, surgery etc) for the recurrent
disease.

- Phase II Component: The subjects must not have been curatively operated for the
disease.

3. Subjects must have completed any prior chemotherapy, biologic/targeted anti-cancer
therapy or surgery at least 4 weeks (at least 6 weeks for nitrosureas and mitomycin
C) before initiation of protocol treatment and subjects must have recovered (to < or
= grade 1) from the toxic effects from any prior therapy

4. Measurable disease as per RECIST criteria.

5. Age > or = 18 years

6. ECOG (Eastern Cooperative Oncology Group) performance status < or = 2

7. Life expectancy of at least 12 weeks

8. Normal organ and marrow function:

- Hemoglobin > or = 100 g/L

- Leukocytes > or = 3 x 109/L

- Absolute Neutrophil Count (ANC)> or = 1.5 x 109/L

- Platelets > or = 75 x 109/L

- Total bilirubin < or = 1.5 X institutional Upper Limit of Normal (ULN)

- AST(SGOT)< or = 2.5 X institutional ULN

- ALT(SGPT)< or = 2.5 X institutional ULN

- Creatinine < or = 1.5 X institutional ULN

9. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Nasopharyngeal carcinoma

2. Subjects who had received any other investigational drug within 1 month prior to day
1 of study drug administration or who have not recovered (to < or = grade 1) from
adverse effects of the investigational agent received prior to this period.

3. History of unstable angina or myocardial infarction or stroke within 6 months prior
to initiation of protocol treatment.

4. QTcF > 450 msec

5. Subjects with uncontrolled inter-current illness including, but not limited to active
infection, symptomatic congestive heart failure, cardiac arrhythmia, psychiatric
illness or any condition that would limit compliance with study requirements.

6. Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or
Hepatitis B.

7. Women who are pregnant or lactating.

8. Women of childbearing potential [defined as a sexually mature woman who has not
undergone hysterectomy or who has not been naturally postmenopausal for at least 24
consecutive months (i.e. who has had menses any time in the preceding 24 consecutive
months)] and men, not agreeing to use at least two approved methods of contraception,
including at least one barrier method prior to study entry (after signing the
informed consent document), during the duration of study participation and for at
least 4 weeks after withdrawal from the study drug, unless they are surgically
sterilised.

9. Any condition, including laboratory abnormalities, that in the opinion of the
investigator places the subject at an unacceptable risk or deems the subject not
suitable for participation in the study.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose (MTD) and dose limiting toxicity (ies) (DLT/s) of P276-00 in combination with radiation in subjects with recurrent and/or locally advanced squamous cell carcinoma of head and neck (SCCHN)

Outcome Time Frame:

3 weeks

Safety Issue:

Yes

Principal Investigator

Kirushna Kumar, MD, RT

Investigator Role:

Principal Investigator

Investigator Affiliation:

Meenakshi Mission Hospital & Research Centre, Madurai, India

Authority:

India: Drugs Controller General of India

Study ID:

P276-00/31/08

NCT ID:

NCT00899054

Start Date:

August 2009

Completion Date:

November 2012

Related Keywords:

  • Squamous Cell Carcinoma of Head and Neck
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

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