Squamous Cell Carcinoma
Conditions
Keywords
squamous cell carcinoma, head, neck, aerodigestive
Brief summary
The primary hypothesis of this study is that the addition of mammalian target of rapamycin (mTOR) blockade to conventional epidermal growth factor receptor (EGFR) blockade will result in synergistic clinical activity in Squamous Cell Carcinoma of the Head and Neck (SCCHN), consistent with preclinical xenograft data. Patients will be treated with the combination of temsirolimus and erlotinib, at the previously established Maximal Tolerated Dose (MTD). The primary signal of efficacy will be progression free survival (PFS), anticipating that PFS will be prolonged compared to historical PFS in SCCHN patients treated with erlotinib or cetuximab monotherapy.
Detailed description
This is a phase II, multicenter, single arm, open-label study. Thirty-seven patients with advanced, platinum-refractory or platinum-ineligible squamous cell carcinoma of the head and neck will be sequentially enrolled to a single treatment arm. Patients will be treated with continuous, 28-day cycles of 150 mg of erlotinib by mouth daily and 15 mg of temsirolimus intervenously weekly. In the absence of grade 3 or higher toxicity in the first cycle, a single, intra-patient dose increase to 20 mg temsirolimus will be permitted.
Interventions
DRUGErlotinib
Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
DRUGTemsirolimus
In the absence of Grade 3 or higher toxicity, a single, intra-patient dose increase of temsirolims to 20 mg intravenously weekly is permitted after the first 28 day cycle. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of informed consent.
Sponsors
Genentech, Inc.
New Mexico Cancer Research Alliance
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, from any primary site. Nasopharyngeal carcinoma, World Health Organization (WHO) Grade I, will be included. 2. Advanced disease, fulfilling one of the criteria defined below: * Incurable disease as assessed by surgical or radiation oncology * Metastatic (M1) disease * Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity 3. Platinum-refractory or platinum-ineligible, fulfilling one of the criteria defined below: * disease progression during or after 4-6 cycles of platinum-containing therapy in the advanced setting * disease progression within 6 months of curative-intent treatment, which included platinum-based chemotherapy * ineligible for platinum-containing therapy, in the opinion of the medical oncologist, due to medical comorbidities or unacceptable risk for toxicity * patient refuses platinum-containing therapy 4. Measurable disease based on response evaluation criteria in solid tumors (RECIST) \- disease in previously irradiated sites is considered measurable if there has been unequivocal progression of the lesion after radiotherapy, or the lesion contains residual carcinoma by biopsy more than 6 weeks after completion of radiotherapy 5. Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed consent 6. Adequate hematologic reserve and organ function * Absolute neutrophil count \> 1200/µl * Platelet count \> 100,000/µl * Renal function: Serum Creatinine ≤ 1.5x upper limit of normal (ULN) * Liver function: Total bilirubin ≤ 1.5x ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN 7. Able to provide written, voluntary consent 8. Patients with reproductive potential must use an effective contraceptive method. 9. Male or female, age ≥ 18 years 10. Life expectancy ≥ 12 weeks
Exclusion criteria
1. Nasopharyngeal primary site, if WHO grade II or III 2. Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced disease setting 3. Prior treatment blocking EGFR in the curative-intent setting, if delivered in the previous 6 months 4. Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR) 5. Sensitivity to temsirolimus or erlotinib 6. Uncontrolled metastatic disease of the central nervous system 7. Radiotherapy within the 2 weeks before Cycle 1' Day 1 8. Surgery within the 2 weeks before Cycle 1' Day 1 9. Pregnant or lactating females 10. Myocardial infarction or ischemia within the 6 months preceding study treatment 11. Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications 12. No other concurrent, investigational anti-neoplastic agent will be permitted 13. History of prior malignancy within the prior five years, with the exception of non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 3 years | The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or unequivocal progression of existing non-target lesion, the appearance of new lesions, death due to disease without prior objective documentation of progression, or global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity Profile | 3 years | Toxicities (i.e. Adverse Events) are evaluated prior to each treatment and during any clinical visit. Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The number of patients affected by adverse events of grade 3 or higher will be reported. |
| Overall Response Rate (ORR) | 3 years | Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is the sum of the percentages of patients achieving complete and partial responses |
| Overall Survival (OS) | 3 years | The time from treatment initiation to death by any cause |
Countries
United States
Participant flow
Recruitment details
Dates of recruitment period: December, 2009 - March, 2011
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib and Temsirolimus Erlotinib at 150 mg by mouth daily + Temsirolimus at 15 mg intravenously weekly. Each cycle is comprised of 28 days. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Treatment-unrelated death | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erlotinib and Temsirolimus |
|---|---|
| Age, Continuous | 61.5 years |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 4 / 12 |
Outcome results
Primary
Progression Free Survival (PFS)
The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI): Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or unequivocal progression of existing non-target lesion, the appearance of new lesions, death due to disease without prior objective documentation of progression, or global deterioration in health status attributable to disease requiring a change in therapy without objective evidence of progression.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Temsirolimus | Progression Free Survival (PFS) | 1.9 Months |
Secondary
Overall Response Rate (ORR)
Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by computerized tomography (CT) or magnetic resonance imaging (MRI:) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is the sum of the percentages of patients achieving complete and partial responses
Time frame: 3 years
Population: Participants evaluable for response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib and Temsirolimus | Overall Response Rate (ORR) | Complete response (CR) | 0 percentage of evaluable participants |
| Erlotinib and Temsirolimus | Overall Response Rate (ORR) | Partial response (PR) | 11.1 percentage of evaluable participants |
| Erlotinib and Temsirolimus | Overall Response Rate (ORR) | Overall response rate (CR + PR) | 11.1 percentage of evaluable participants |
Secondary
Overall Survival (OS)
The time from treatment initiation to death by any cause
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Temsirolimus | Overall Survival (OS) | 4 months |
Secondary
Toxicity Profile
Toxicities (i.e. Adverse Events) are evaluated prior to each treatment and during any clinical visit. Toxicity will be evaluated per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The number of patients affected by adverse events of grade 3 or higher will be reported.
Time frame: 3 years
Population: Participants who received t least one dose of on-study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib and Temsirolimus | Toxicity Profile | Diarrhea | 2 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Facial/neck edema | 1 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Laryngeal edema | 1 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Asthenia | 5 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Peritonitis / infection | 2 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Anorexia | 1 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Elevated triglycerides | 1 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Aspiration pneumonia | 1 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Dyspnea | 3 participants |
| Erlotinib and Temsirolimus | Toxicity Profile | Hypoxia | 1 participants |