Safety and Efficacy Study of P276-00 in Combination With Radiation in Subjects With Advanced Head and Neck Cancer

NCT00899054 | Completed Phase 1 DMC

• 1 other identifier: P276-00/31/08
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to identify a dose of P276-00 that can be safely administered along with Radiation and to examine safety and efficacy of the combination in treatment of advanced head and neck cancer.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• 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)

  3 weeks

Secondary Outcomes (4)

• To evaluate safety and tolerability of the combination regimen of P276-00 and radiation in the study population

  Every week

• To analyze pharmacokinetics (PK) of P276-00 in the study population

  Day 2 and Day 5 of Cycle 1

• To evaluate efficacy of the combination regimen of P276-00 and radiation in the study population

  Every 6 weeks

• To perform exploratory analysis of biomarkers associated with use of P276-00 and radiation in the study population

  Day 1 and Day 4

Study Arms (1)

P276-00 plus Radiation

EXPERIMENTAL

P276-00: Level 1:100 mg/m2/day x 5 q 3 weeks, level 2:140 mg/m2/day x 5 q 3 weeks, level 3: 185 mg/m2/day x 5 q 3 weeks. External beam radiotherapy (EBRT): 2 Gy per day for 5 days a week for a total radiation dose of 60 Gy over 2 cycles (6 weeks)followed by upto 10 additional Gy if required

Drug: P276-00; Radiation: External beam radiotherapy (EBRT)

Interventions

P276-00 DRUG

P276-00 will be administered at different dose levels: level 1: 100 mg/m2/day dose level 2: 140 mg/m2/day dose level 3: 185 mg/m2/day to be given from day 1 to day 5 every 21 days for 2 cycle. P276-00 will be administered as intravenous infusion in 200 ml 5% Dextrose over 30 min from days 1 to 5 per 21 day cycle for two cycles.

P276-00 plus Radiation

External beam radiotherapy (EBRT) RADIATION

All subjects will receive external beam radiotherapy (EBRT)by using standard conventional fractionation i.e. 2 Gy per day for 5 days a week for a total radiation dose of 60 Gy over 6 weeks followed by upto 10 additional Gy if required.

Also known as: Radiotherapy

P276-00 plus Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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
• Measurable disease as per RECIST criteria.
• Age \> or = 18 years
• ECOG (Eastern Cooperative Oncology Group) performance status \< or = 2
• Life expectancy of at least 12 weeks
• 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

You may not qualify if:

• Nasopharyngeal carcinoma
• 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.
• History of unstable angina or myocardial infarction or stroke within 6 months prior to initiation of protocol treatment.
• QTcF \> 450 msec
• 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.
• Subjects known to be suffering from infection with HIV, Tuberculosis, Hepatitis C or Hepatitis B.
• Women who are pregnant or lactating.
• 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.
• 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.

Sponsors & Collaborators

• Piramal Enterprises Limited: lead

Study Sites (6)

Government Medical College

Aurangabad, Maharashtra, 431001, India

Location

Curie Manavata Cancer Center

Nashik, Maharashtra, 422 004, India

Location

Bhagwan Mahawir Cancer Hospital & Research Centre

Jaipur, Rajasthan, 302017, India

Location

V. N. Cancer Centre, GKNM Hospital

Coimbatore, Tamil Nadu, 641037, India

Location

Meenakshi Mission Hospital & Research Centre

Madurai, Tamil Nadu, 625107, India

Location

Christian Medical College

Vellore, Tamil Nadu, 632 004, India

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

P276-00; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Kirushna Kumar, MD, RT

  Meenakshi Mission Hospital & Research Centre, Madurai, India

  PRINCIPAL INVESTIGATOR

• Raj Nagarkar, MS

  Curie Manavata Cancer Center, Nashik, India

  PRINCIPAL INVESTIGATOR

• Subhashini John, MD, DMRT

  Christian Medical College, Vellore, India

  PRINCIPAL INVESTIGATOR

• Balaji Shewalkar, MD, DNB

  Government Medical College, Aurangabad, India

  PRINCIPAL INVESTIGATOR

• M. Nagarajan, MD, DNB

  V. N. Cancer Centre, GKNM Hospital, Coimbatore, India

  PRINCIPAL INVESTIGATOR

• Naresh Somani, DM

  Bhagwan Mahawir Cancer Hospital & Research Centre, Jaipur, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2009
• First Posted: May 12, 2009
• Study Start: August 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: November 1, 2012
• Last Updated: November 22, 2012

Record last verified: 2012-11

Locations

IN (6)