Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

3E10 TCID50, 1 hour intravenous infusion, administered on Days 1, 2, 3, 4 and 5 of a 21 day cycle

REOLYSIN

5 AUC mg/mL min, 30 min intravenous infusion, given on Day 1 of a 21 day cycle

175 mg/m2, 3 hour intravenous infusion, given on Day 1 of a 21 day cycle

Placebo

James A Bonner, MD

Kevin Harrington, MBBS MRCP FRCR

Jan Vermorken, MD, PhD

The purpose of this Phase 3 study is to evaluate overall survival and progression free survival following intravenous administration of REOLYSIN (Reovirus Serotype 3 Dearing) in combination with paclitaxel and carboplatin versus chemotherapy treatment alone, in patients with metastatic or recurrent Squamous Cell Carcinoma of the Head and Neck.

Squamous cell carcinoma of the head and neck is the sixth most common cancer in the world. More than 50% of patients diagnosed with advanced regional disease will relapse locally or at distant sites. Initial therapeutic options include irradiation, surgery and chemotherapy. The most commonly used agents are cisplatin and carboplatin, generally in combination with 5-FU or a taxane. Erbitux has been approved for use in first-line with radiation and in second-line as monotherapy. Only about a third of the patients will respond to first-line platinum-based therapy and the median overall survival is about 6-9 months.

Preliminary assessment of a Phase 1-2 study conducted in the UK investigating the combination of REOLYSIN, carboplatin and paclitaxel suggested that patients with head and neck carcinomas may represent a group of patients in whom this treatment combination is active. Studies have also shown that paclitaxel and carboplatin combination therapy may be effective in head and neck cancers, even in heavily pretreated patients and those resistant to previous treatment. These results strongly support the utility of the carboplatin/paclitaxel combination as a control arm for salvage therapy in platinum refractory patients, a patient group with few and poor treatment options and with no gold standard therapy.

This Phase 3 study is designed to compare response rates following intravenous administration of REOLYSIN (Reovirus Type 3 Dearing) in combination with paclitaxel and carboplatin versus chemotherapy treatment alone, in patients with metastatic or recurrent Squamous Cell Carcinoma of the Head and Neck.

Overall survival is a primary endpoint of this trial. Patients will be clinically evaluated after each course of treatment and radiologically every 6 weeks on and after treatment. The safety of the paclitaxel and carboplatin with intravenous blinded placebo or intravenous blinded REOLYSIN will also be assessed.

Efficacy Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers

Randomized, Double-blind, Multicenter Two-Stage Adaptive Phase 3 Study of Intravenous Administration of REOLYSIN (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin Versus the Chemotherapy Alone in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck Who Have Progressed on or After Prior Platinum-Based Chemotherapy

Oncolytics Biotech

Cetuximab

Cisplatin

Antineoplastic Agents, Immunological

* Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
* If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cisplatin which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
* It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

* Six weeks of nab-paclitaxel (100 mg/m2/week) followed by primary tumor site (PTS) assessment
* If CR/PR, three more weeks of nab-paclitaxel followed by CRT
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cetuximab and will begin 1 to 35 days after completion of cycle -Cetuximab will be started 7 days before starting definitive radiation therapy. The initial loading dose of cetuximab will be 400 mg/m\^2. Subsequently, cetuximab will be given weekly at a dose of 250 mg/m\^2 for seven additional doses concurrently with radiation therapy.
* It is strongly recommended that IMRT begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

* 6 weeks of nab-paclitaxel and cisplatin (days 1 \& 22) followed by primary tumor site assessment
* If CR/PR, cycle 3 of induction then 42Gy radiation, 1 dose of cisplatin or 6 doses cetuximab
* If SD/PD: undergo surgery if candidate followed by CRT with 42 Gy RT and abbreviated cisplatin or cetuximab or 70Gy RT and 3 cycles of cisplatin or 8 doses of cetuximab
* CRT includes Cisplatin and will begin 1-35 days after the completion of Cycle 3 of induction. Cisplatin will be given as 1 dose during the initial 5 days of definitive radiation therapy
* Strongly recommended that radiation therapy begin within 28-49 days (and no later than 56 days) after the start of Cycle 3. Intensity modulated radiation therapy is to be used exclusively for this study.

nab-Paclitaxel

Intensity-Modulated Radiation Therapy

Douglas Adkins, M.D.

In this trial, the objectives are to determine the efficacy and toxicity of induction chemotherapy (IC) with nab-paclitaxel + cisplatin (Arm 1: AP) and with nab-paclitaxel (Arm 2: A) alone in patients with HNSCC, and to compare these data to nab-paclitaxel, cisplatin, and 5-FU (APF). The investigators also hypothesize that the high anti-tumor efficacy of nab-paclitaxel in HNSCC is due to the upregulation of macropinocytosis, a result of the frequent presence of Ras and PI3K (and epidermal growth factor receptor -EGFR) activation in this cancer.

Amendment to Add Arm 3:

In this amendment, the investigators retain the AP + concurrent chemoradiation therapy (CRT) backbone but de-escalate the dose of radiation therapy (RT) from 70 Gy to 42 Gy. The investigators also plan to administer one dose (vs three) of cisplatin during RT. This novel treatment approach will be evaluated in patients with HPV-related oropharyngeal squamous cell carcinoma (OPSCC) (Arm 3), a sub-group with a very favorable prognosis.

Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)

Phase II Non-Randomized Three Arm Trial of Induction Chemotherapy With Nab-Paclitaxel and Cisplatin (AP: Arms 1 and 3) or Single Agent Nab-paclitaxel (A: Arm 2) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC): "The APA Trial".

* Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ear, nose, and throat (ENT) physician's clinical exam note.
* Complete response = complete resolution - 100% decrease/minimal residual mucosal abnormality

* Assessment of primary tumor site will be done by laryngoscopy performed in the office or in the operating room. The primary tumor response to the first two cycles of induction will be assessed using visual categorical response. The percent change from baseline will be dictated in the ENT physician's clinical exam note.
* Partial response - 99-50% decrease

* The involved neck node response to the first two cycles of induction will be assessed using visual categorical response. The neck node measurements will be performed clinically by the treating medical oncology physician and dictated in his/her assessment note.
* Complete response - complete resolution - 100% decrease/minimal residual mucosal abnormality

* The involved neck node response to the first two cycles of induction will be assessed using visual categorical response. The neck node measurements will be performed clinically by the treating medical oncology physician and dictated in his/her assessment note.
* Partial response - 99%-50% decrease

-Computed tomography (CT) scan (intravenous contrast preferred) to document and measure the extent of the primary tumor size and involved regional neck nodes. RECIST 1.1 will be used to determine response at the primary tumor site, at the involved regional neck nodes and the radiographic overall tumor response.

Compare to those observed with APF with the objective that Arm 1 will be at least 25% lower than the risk of Grade 3-4 AE's during APF (40% decreased to 30%) and Arm 2 will be at least 50% lower than the risk of Grade 3-4 AE's during APF (40% decreased to 20%).

-The FACT/GOG-NTX-4 questionnaire has 4 questions about neuropathy (numbness/tingling in hands/feet and discomfort in hands/feet) with answers ranging from 0 (Not at all) to 4 (Very Much). The total score ranges from 0 to 16. A lower score indicates less neuropathy symptoms.

-The FACT-H\&N has 5 domains with 39 items including physical well-being (PWB), social/family well being (SWB), emotional well-being (EWB), functional well-being (FWB), and head \& neck cancer (HNCS) with answers ranging from 0 (Not at all) to 4 (Very Much). The PWB subscale score ranges from 0-28. The SWB subscale score ranges from 0-28. The EWB subscale score ranges from 0-24. The FWB subscale score ranges from 0-28. The HNCS subscale score ranges from 0-40. To obtain the total score all subscales are added together. The total score ranges from 0-148 with a higher score indicating a better quality of life.

OS: duration of time from date of diagnosis to late date alive or time of death from any cause.

OS: duration of time from date of diagnosis to last date alive or time of death from any cause.

DFS: duration of time from last date of treatment to time of disease progression or death from any cause.

◦PFS: duration of time from date of diagnosis to time of disease progression or death from any cause, whichever occurs first.

OS: duration of time from start of treatment to time of death from any cause

◦PFS: duration of time from start of treatment to time of progression or death, whichever occurs first.

Celgene Corporation

Washington University School of Medicine

-Participants at risk is zero for Other (Not Including Serious) Adverse Events for Arm 1 Follow-up, Arm 2 Follow-up, and Arm 3 Follow-up because adverse events were not collected in the follow-up period.

* Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
* If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
* If \<PR, move directly to CRT if not surgical candidates.

Arm 1: Nab-Paclitaxel and Cisplatin (AP) Induction

* Six weeks of nab-paclitaxel (100 mg/m2/week) followed by primary tumor site (PTS) assessment
* If CR/PR, three more weeks of nab-paclitaxel followed by CRT
* If \<PR, move directly to CRT if not surgical candidates.

Arm 2: Nab-Paclitaxel (A) Induction

* 6 weeks of nab-paclitaxel and cisplatin (days 1 \& 22) followed by primary tumor site assessment
* If CR/PR, cycle 3 of induction then 42Gy radiation, 1 dose of cisplatin or 6 doses cetuximab
* If SD/PD: undergo surgery if candidate followed by CRT

Arm 3: Nab-Paclitaxel and Cisplatin (AP) Induction

* CRT includes cisplatin which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
* It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

Arm 1 CRT: Cisplatin + Radiation Therapy

* CRT includes cetuximab and will begin 1 to 35 days after completion of cycle -Cetuximab will be started 7 days before starting definitive radiation therapy. The initial loading dose of cetuximab will be 400 mg/m\^2. Subsequently, cetuximab will be given weekly at a dose of 250 mg/m\^2 for seven additional doses concurrently with radiation therapy.
* It is strongly recommended that IMRT begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

Arm 1 & 2 ERT: Cetuximab + Radiation Therapy

* CRT includes Cisplatin and will begin 1-35 days after the completion of Cycle 3 of induction. Cisplatin will be given as 1 dose during the initial 5 days of definitive radiation therapy
* Strongly recommended that radiation therapy begin within 28-49 days (and no later than 56 days) after the start of Cycle 3. Intensity modulated radiation therapy is to be used exclusively for this study.

Arm 3 CR: Cisplatin + Radiation Therapy

-Follow-up time period of up to 72 months post-completion of therapy

Arm 1: Nab-Paclitaxel+Cisplatin+CRT Follow-up

Arm 2: Nab-Paclitaxel + ERT Follow-up

Arm 3: Nab-Paclitaxel+Cisplatin+Modified CRT Follow-up

* Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
* If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cisplatin (if cannot receive cisplatin will receive cetuximab) which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
* It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

Arm 1: Nab-Paclitaxel and Cisplatin (AP) + CRT

Arm 2: Nab-Paclitaxel (A) + CRT

Arm 3: Nab-Paclitaxel and Cisplatin (AP) + Modified CRT

-Determined to be not eligible after enrollment to study and was therefore not enrolled on any study arm.

Not Enrolled in Any Arm

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Douglas R. Adkins, M.D.

Only participants enrolled in Arm 1 and Arm 2 are evaluable for this outcome measure.

Arm 1 and Arm 2: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site

Only participants enrolled in Arm 3 are evaluable for this outcome measure.

Arm 3: Median Percent Weight Loss

Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Primary Tumor Site

Arms 1, 2 and 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Involved Regional Nodes

Arms 1, 2, and 3: Clinical Partial Response Rate as Measured by Clinical Exam at the Involved Regional Nodes

Complete response

Partial response

Arms 1, 2, and 3: Anatomic Tumor Response as Assessed by CT Using RECIST 1.1 Criteria

The data was not collected for this outcome measure.

Arms 1, 2, and 3: Document and Quantify Ki-67 Expression by IHC in Primary Tumor Tissue and Correlate With Clinical Primary Tumor Site Response

Arms 1, 2, and 3: Number of Participants Who Experienced a Grade 3-4 Adverse Event as Measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

Baseline

End of treatment

Arms 1, 2, and 3: Mean Total Score as Measured by the FACT/GOG-NTX-4

Arms 1, 2, and 3: Mean Total Score as Measured by FACT-H&N

2 participants were excluded in Arm 3 because they received full dose radiation therapy instead of reduced dose radiation therapy.

Arms 1, 2, and 3: Kaplan-Meier Estimate of Overall Survival (OS)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Disease-free Survival (DFS)

Arms 1, 2, and 3: Kaplan-Meier Estimate of Progression-free Survival (PFS)

Arm 3: Clinical Complete Response Rate as Measured by Clinical Exam at the Primary Tumor Site

Data was not collected for this outcome measure.

Arm 1 and Arm 3: Comparison of Response Rate

Arm 1 and Arm 3: Comparison of the Rate of Grade 3/4 Adverse Events

Comparison of Median Absolute Weight Loss in Arms 2 and 3 to Arm 1

Comparison of Median Percent Weight Loss in Arms 2 and 3 to Arm 1

Arms 1, 2, and 3: Overall Survival (OS)

Arms 1, 2, and 3: Progression-free Survival (PFS)

Arms 1, 2, and 3: Disease-free Survival (DFS)

Arm 1 and Arm 3: Comparison of Overall Survival

Arm 1 and Arm 3: Comparison of Disease-free Survival

Arm 1 and Arm 3: Comparison of Progression-free Survival

* Six weeks of nab-paclitaxel (100 mg/m2/week) and cisplatin (75 mg/m2 days 1 and 22) followed by primary tumor site (PTS) assessment
* If complete response (CR)/partial response (PR), three more weeks of nab-paclitaxel and cisplatin followed by concurrent chemoradiation therapy (CRT)
* If \<PR, move directly to CRT if not surgical candidates.
* CRT includes cisplatin (if cannot receive cisplain will receive cetuximab) which will begin 1 to 35 days after the completion of cycle 3. The first dose of cisplatin will be given during the initial 5 days of definitive radiation therapy, the second on approximately Day 22 of radiation, and the third on approximately Day 43 of radiation.
* It is strongly recommended that intensity-modulated radiation therapy (IMRT) begin within 21 to 42 days (no later than 56 days) after the start of cycle 3. The total dose will be 7000 cGy in 35 fractions of 200 cGy each over 7 weeks. A dose of 6300 cGy in 35 fractions is optional and may be delivered to areas considered to be an intermediate risk.

Overall Study

REOLYSIN®

Monica Mita, MD

The purpose of this Phase 2 study is to investigate whether intravenous administration of REOLYSIN® therapeutic reovirus in combination with Paclitaxel and Carboplatin is effective and safe in the treatment of squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck is the sixth most common cancer in the world. More than 50% of patients diagnosed with advanced regional disease will relapse locally or at distant sites. Initial therapeutic options include irradiation, surgery and chemotherapy. The most commonly used agents are cisplatin and carboplatin, generally in combination with 5-FU or a taxane. Erbitux has recently been approved for use in first-line with radiation and in second-line as monotherapy. Only about a third of the patients will respond to first-line platinum-based therapy and the median overall survival is 6-9 months.

Preliminary assessment of a Phase 1 study being conducted in the UK investigating the combination of REOLYSIN®, carboplatin and paclitaxel suggested that patients with head and neck carcinomas may represent a group of patients in whom this treatment combination is active.

This Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN® given intravenously in combination with paclitaxel and carboplatin every 3 weeks in patients with squamous cell carcinoma of the head and neck.

Response is a primary endpoint of this trial. Patients will be clinically evaluated after each course of treatment and radiologically every other cycle. A complete or partial response must be confirmed at least 4 weeks after the first assessment that documents such a response and every two cycles thereafter.

The safety of the paclitaxel, carboplatin and REOLYSIN® combination will be assessed by the evaluation of the type, frequency and severity of adverse events, changes in clinical laboratory tests, immunogenicity and physical examination.

Patients may continue to receive therapy under this protocol, provided they have not experienced either progressive disease or unacceptable drug-related toxicity that does not respond to either supportive care or dose reduction.

Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Head and Neck Carcinoma

Phase 2 Study of Intravenous Administration of a Wild-Type Reovirus (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers	NCT01166542	Carcinoma, Squa...	REOLYSIN Carboplatin Paclitaxel Placebo	18 Years -	Oncolytics Biotech
Nab-Paclitaxel and Cisplatin or Nab-paclitaxel as Induction Therapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)	NCT02573493	Squamous Cell C... Carcinoma, Squa... Cancer of Head ... Cancer of the H... Head and Neck C... Neoplasms, Head...	nab-Paclitaxel Cisplatin Cetuximab Intensity-Modul...	18 Years -	Washington University School of Medicine
Efficacy Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Platinum-Refractory Head and Neck Cancers	NCT01166542	Carcinoma, Squa...	REOLYSIN Carboplatin Paclitaxel Placebo	18 Years -	Oncolytics Biotech
Phase 2 Study of REOLYSIN® in Combination With Paclitaxel and Carboplatin in Patients With Head and Neck Carcinoma	NCT00753038	Carcinoma, Squa...	REOLYSIN® Carboplatin Paclitaxel	18 Years -	Oncolytics Biotech

Spots Global Cancer Trial Database for carcinoma, squamous cell of the head and neck