NCT02573493|CompletedPhase 2ResultsDMCFDA Drug

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

APA

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".

Washington University School of Medicine ClinicalTrials.gov

Compare

Other study identifiers

Sponsor study identifier

201510013

Study Type

interventional

Actual enrollment (reported)

Locations

1 country

Sites

Timeline

Study Start

April 13, 2016

Actual (reported)

Primary Completion

December 12, 2019

Actual (reported)

Study Completion

July 1, 2024

Actual (reported)

Brief Summary

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.

Registry Overview

Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.

Recruitment status: completed
Actual enrollment (reported): 96 participants
Study completion date: July 1, 2024
Actual (reported)
Listed locations: 1 countries · 3 sites

Trial Relationships

Click on a node to explore related trials.

Some registry-reported names shown below are not yet linked in this graph.

Study Timeline

Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.

First Submitted
October 7, 2015
Actual (reported)
First Posted
October 9, 2015
Actual (reported)
Study Start
April 13, 2016
Actual (reported)
Primary Completion
December 12, 2019
Actual (reported)
Results Posted
March 2, 2021
Actual (reported)
Study Completion
July 1, 2024
Actual (reported)

Last Updated: December 27, 2024
Status Verified: December 2024
Results QC Date: February 27, 2021
Last Update Submitted: December 2, 2024

Conditions

Cancer of Head and Neck Cancer of the Head and Neck Carcinoma, Squamous Cell of the Head and Neck Head and Neck Cancer Neoplasms, Head and Neck Squamous Cell Carcinoma of the Head and Neck

Study Arms (3)

Arm 1: nab-Paclitaxel and cisplatin (AP) + CRT

EXPERIMENTAL

* 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.

Drug: nab-PaclitaxelDrug: CisplatinRadiation: Intensity-Modulated Radiation Therapy

Arm 2: nab-Paclitaxel (A) + CRT

EXPERIMENTAL

* 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.

Drug: nab-PaclitaxelBiological: CetuximabRadiation: Intensity-Modulated Radiation Therapy

Arm 3: nab-Paclitaxel and cisplatin (AP) + modified CRT

EXPERIMENTAL

* 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.

Drug: nab-PaclitaxelDrug: CisplatinRadiation: Intensity-Modulated Radiation Therapy

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Diagnosis of selected Stage III or IVa/b HNSCC. Arm 1: T2-T4 primary tumors. Arm 3: T2T1-T4 primary tumors. Although most of these patients will have regional nodal disease, patients with no nodal disease will also be eligible.
Arm 1: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites.
Arm 3: Presence of disease at the oropharynx sub-sites, which is HPV-related as verified by p16, a surrogate marker of HPV, or HPV ISH or PCR.
Presence of measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan.
At least 18 years of age.
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 3 months after completing treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Able to understand and willing to sign an IRB-approved written informed consent document.
ECOG performance status ≤ 1.
Adequate bone marrow and organ function as defined below:
ANC: ≥ 1500/mcL.
Platelets: \> 100,000/mcL.
Hemoglobin \> 9.0 g/dL
Total bilirubin ≤ 1.5 mg/dL
AST/ALT/alkaline phosphatase: ≤ 2.5 x ULN.
Serum creatinine: \< 1.5 mg/dL or calculated GFR ≥ 75 cc/min. CrCl by Cockcroft Gault will be used to estimate GFR.
+18 more criteria

You may not qualify if:

Prior chemotherapy, prior EGFR targeted therapy, or prior radiation therapy for HNSCC.
Disease at the nasopharyngeal, sinus, oral cavity, or other sub-site not specified as eligible.
Diagnosis of unknown primary squamous cell carcinoma of the head and neck.
History of prior invasive malignancy diagnosed within 3 years prior to study enrollment; exceptions are malignancies with a negligible risk of metastasis or death (e.g., expected 5-year OS \> 90%) that were treated with an expected curative outcome, such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

Contact the study team to confirm eligibility.

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

First Posted

Study Start

Primary Completion

Results Posted

Study Completion

Conditions

Outcome Measures

Primary Outcomes (2)

Secondary Outcomes (25)

Study Arms (3)

Arm 1: nab-Paclitaxel and cisplatin (AP) + CRT

Arm 2: nab-Paclitaxel (A) + CRT

Arm 3: nab-Paclitaxel and cisplatin (AP) + modified CRT

Interventions

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (3)

Related Publications (1)

Related Links

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Enrollment

Study Design

Study Record Dates

Data Sharing

Source record

Documents

Locations