Clinical Trials: Past Studies

Over the past two decades, about 20 Phase II clinical trials were designed specifically for ACC patients or for salivary gland cancer patients with a large group of ACC patients. These trials are listed in the table below. It is not an exhaustive list as it excludes some smaller studies with fewer than 9 ACC patients as well as some privately-funded studies that were not published. Chemical names are used for each compound with trade names included in parentheses. Hyperlinks provide general descriptions of the drugs as well as published articles or abstracts on each study.

Completed Phase II Clinical Trials with ACC Patients

Compound	Target(s)	Institution	ACC Patients	Objective Response	Stable Disease	Clinial Benefit	Progression Required?	Publication Year	Link
Sunitinib (Sutent)	PDGFR, VEGFR, CKIT, RET	Princess Margaret Hospital	13	0%	85%	62%	Yes	2011	View
Cetuximab (Erbitux)	EGFR	Istituto Nazionale dei Tumori	23	0%	87%	52%		2009	View
Gemcitabine & Cisplatin	Chemotherapy	NCI Canada	10	20%	NA			2009	View
Gemcitabine	Chemotherapy	Radboud University Nijmegen	21	0%	52%	48%		2008	View
Lapatinib (Tykerb)	EGFR, HER2	Princess Margaret Hospital	19	0%	79%	47%	Yes	2007	View
Bortezomib (Velcade)	NFKB, 26S Proteasome	University of Pittsburgh/ECOG	25	0%	64%		Yes	2006	View
Gefitinib (Iressa)	EGRF	MD Anderson	19	0%	68%		Yes	2005	View
Imatinib & Cisplatin	ABL, CKIT, PDGFR	Christie Hospital NHS Trust	28	11%	68%		Yes	2011	View
Imatinib (Gleevec)	ABL, CKIT, PDGFR	Tel Aviv University	10	0%	70%			2007	View
Imatinib (Gleevec)	ABL, CKIT, PDGFR	Princess Margaret Hospital	15	0%	56%			2005	View
Paclitaxel	Chemotherapy	LSU/ECOG	13	0%	54%			2006	View
Paclitaxel & Carboplatin	Chemotherapy	University of Torino	10	20%	NA		Yes	2000	View
Vinorelbine & Cisplatin	Chemotherapy	University of Torino	9	44%	NA		Yes	2001	View
Vinorelbine	Chemotherapy	University of Torino	13	15%	NA		Yes	2001	View
Epirubicin	Chemotherapy	Free University Hospital (NL)	20	10%	50%		Yes	1993	View
Cisplatin & 5-FU	Chemotherapy	Royal Marsden NHS Trust	11	0%	55%			1997	View
Cisplatin & Doxorubicin & Cyclophosphamide	Chemotherapy	Istituto Nazionale dei Tumori	12	25%	42%		Yes	1996	View
Cisplatin & Doxorubicin & Bleomycin	Chemotherapy	Radboud University Nijmegen	9	33%	55%			1992	View
Cisplatin	Chemotherapy	Radboud University Nijmegen	10	0%	50%			1992	View
Cisplatin	Chemotherapy	Istituto Nazionale dei Tumori	13	15%	46%			1991	View
Mitoxantrone	Chemotherapy	Rotterdam Cancer Institute	32	12%	69%			1996	View
Mitoxantrone	Chemotherapy	Johns Hopkins	18	6%	67%			1990	View

Download Completed Phase II Clinical Trials with ACC Patients

In reviewing the history of Phase II clinical trials in ACC, it is important to take note of two key factors:

Progression Requirements – Did the clinical trial require ACC patients to have documented progression (tumor growth greater than 20%) prior to starting therapy? ACC patients with metastases may have long periods of stable disease, making it difficult to determine whether stable disease was the result of the drug. Clinical trials that require progression give a better indication of the drug’s effectiveness.
Clinical Benefit – Did the patient have an objective response (tumor shrinkage of at least 30%) or stable disease, either of which lasted longer than 6 months? Sometimes patients have rapid tumor shrinkage that qualifies as an objective response, but then there is a rapid reversal and progression. Or a slow-growing ACC tumor, unaffected by the drug, may take 3 months to reach 20% growth; the patient will be classified as having stable disease despite the drug’s lack of efficacy. By using a longer horizon, this metric attempts to measure meaningful patient benefit.

Patients should keep in mind that objective responses and stable disease are measures of tumor volume, not overall survival. It is reasonable to assume that smaller tumors mean a longer lifespan, but it is not always the case. Once a treatment stops being effective, tumors may grow back more quickly. Patients must weigh the potential side effects of any treatment against the possibility of extended survival and reduced pain from tumor shrinkage.

The broad conclusion to be drawn from the history of clinical trials with ACC patients is that some standard chemotherapies produce objective responses or clinical benefit in small subsets of ACC patients, but none have been shown to have broad effectiveness, long durations of response or an impact on survival. ACCRF’s affiliated researchers are working hard to come up with very effective therapies and a cure for ACC. In the meantime, however, there is a dire need for drugs that can delay progression. A good starting point is to focus on those clinical trials that had disease progression as an eligibility criterion and had high rates of clinical benefit:

Sunitinib – 8 of 13 progressing patients (62%) had stable disease for more than 6 months.
Lapatinib – 10 of 19 progressing patients (47%) had stable disease for more than 6 months.
Vinorelbine & Cisplatin – 4 of 9 progressing patients (44%) had objective responses of undisclosed length.

Progressing ACC patients without access to clinical trials may wish to discuss these results with their physicians. In addition, they should keep in mind the promising Phase I results of Vorinostat as the ACC community awaits the Phase II results.

Patients enrolling in clinical trials perform an incredibly honorable service for the entire patient community. Without them, it would not be possible to determine systematically whether a particular treatment is effective or safe. Even clinical trials that show that a drug is ineffective are incredibly valuable as future patients are spared the unnecessary side effects and try more promising drugs. Some physicians prescribe approved cancer drugs “off-label” (i.e., approved for tumor types different from the treated tumor) to their patients who cannot travel to or do not qualify for a clinical trial. Unfortunately, those results are not tabulated and shared with others as is the case with clinical trials. Without a doubt, current ACC patients owe a debt of gratitude to those who have helped guide our current understanding of how ACC responds to systemic therapies.

For more background and details on clinical trials, please read ACCRF’s Guide to Systemic Therapy for Patients With Progressive ACC.